PMID-sentid Pub_year Sent_text compound_name comp_offset prot_official_name organism prot_offset 23723320-12 2014 OPG-Fc decreased osteoclast number, inhibited the formation of osteophytes and improved structural pathology within the joint similarly to the decrease seen after pretreatment with the bisphosphonate, zoledronate. Diphosphonates 185-199 TNF receptor superfamily member 11B Rattus norvegicus 0-3 24616121-8 2014 In ovariectomized mice cyclicCHAD improved bone mass by both a preventive and a curative treatment protocol, with an effect in line with that of the bisphosphonate alendronate, that was mimicked by the NOS2 inhibitor [L-N6-(1-Iminoethyl)-lysine.2 dihydrochloride]. Diphosphonates 149-163 nitric oxide synthase 2, inducible Mus musculus 202-206 24976061-3 2014 Bisphosphonates have little, if any, effect on lipid metabolism, while they are suggested to improve glucose metabolism, via osteocalcin or adiponectin. Diphosphonates 0-15 bone gamma-carboxyglutamate protein Homo sapiens 125-136 24911392-7 2014 RESULTS: Bisphosphonate users had odds ratios (95% confidence interval) of 1.20 (1.01 to 1.44) and 0.95 (0.74 to 1.24) by applying D1 and D2 designs, respectively. Diphosphonates 9-23 leiomodin 1 Homo sapiens 131-140 25247160-0 2014 Increase in the serum parathyroid hormone level during a bisphosphonate drug holiday. Diphosphonates 57-71 parathyroid hormone Homo sapiens 22-41 24911527-1 2014 Human farnesyl pyrophosphate synthase (hFPPS) is the gate-keeper of mammalian isoprenoids and the key target of bisphosphonate drugs. Diphosphonates 112-126 farnesyl diphosphate synthase Homo sapiens 6-37 24911527-1 2014 Human farnesyl pyrophosphate synthase (hFPPS) is the gate-keeper of mammalian isoprenoids and the key target of bisphosphonate drugs. Diphosphonates 112-126 farnesyl diphosphate synthase Homo sapiens 39-44 24976061-3 2014 Bisphosphonates have little, if any, effect on lipid metabolism, while they are suggested to improve glucose metabolism, via osteocalcin or adiponectin. Diphosphonates 0-15 adiponectin, C1Q and collagen domain containing Homo sapiens 140-151 23837828-0 2014 Interleukin-6 concentration changes in plasma and saliva in bisphosphonate-related osteonecrosis of the jaws. Diphosphonates 60-74 interleukin 6 Homo sapiens 0-13 23837828-1 2014 AIM: To determine the plasma and saliva levels of IL-6 in patients with bisphosphonate-related osteonecrosis of the jaws (BRONJ) and to investigate whether there is a correlation between more advanced stages of BRONJ and levels of IL-6. Diphosphonates 72-86 interleukin 6 Homo sapiens 50-54 24902588-10 2014 Bisphosphonates infusion after lumbar infusion surgery could promote bone healing and shorten fusion time in 6 months postoperation (RR 1.35; 95% CI 1.11 to 1.66). Diphosphonates 0-15 ribonucleotide reductase catalytic subunit M1 Homo sapiens 133-137 24919660-10 2014 Despite this increased fracture rate, individuals with diabetes (insulin-dependent or non-insulin-dependent) were less likely to be on bisphosphonate therapy at any point over 10 years of prospective follow up compared to other CaMos subjects (odds ratio [OR]: 0.59; 95% CI 0.46-0.75, p < 0.001). Diphosphonates 135-149 insulin Homo sapiens 65-72 25130632-6 2014 Moreover, polymorphisms of CYP2C gene, but also FDPS may identify patients with high risk of undesirable effects of bisphosphonates (osteonecrosis of jaw). Diphosphonates 116-131 cytochrome P450 family 2 subfamily C member 19 Homo sapiens 27-32 25130632-6 2014 Moreover, polymorphisms of CYP2C gene, but also FDPS may identify patients with high risk of undesirable effects of bisphosphonates (osteonecrosis of jaw). Diphosphonates 116-131 farnesyl diphosphate synthase Homo sapiens 48-52 24982847-7 2014 With the new generation bisphosphonate zoledronic acid (ZA) or denosumab (anti-RANKL activity), one can reduce the number of patients who experience SREs, decrease the annual incidence of SREs and delay the median time to first SRE. Diphosphonates 24-38 TNF superfamily member 11 Homo sapiens 79-84 24813742-2 2014 Some of the bisphosphonate revealed to be very potent inhibitors (in the low nanomolar range) of the cytosolic isoform CA II and the membrane-bound CA IX, XII and XIV isozymes, a feature useful for considering them as interesting compounds for bone resorption inhibition applications. Diphosphonates 12-26 carbonic anhydrase 9 Homo sapiens 148-153 24390519-13 2014 Even though the study group was small, the findings of the current study (one new fracture and one patient with decreased BMD) call for a larger study to assess the efficacy of bisphosphonates in NF1-related osteoporosis. Diphosphonates 177-192 neurofibromin 1 Homo sapiens 196-199 24636958-7 2014 Here, we demonstrate that bisphosphonates directly inhibit VEGFR2 expression in endothelial cells, as well as endothelial cell proliferation and migration. Diphosphonates 26-41 kinase insert domain receptor Homo sapiens 59-65 24636958-8 2014 Additionally, bisphosphonates also decrease VEGF-A expression in osteosarcoma (K7M3) cells, resulting in reduced stimulation of endothelial cell migration in co-culture assays. Diphosphonates 14-29 vascular endothelial growth factor A Mus musculus 44-50 24636958-11 2014 In conclusion, bisphosphonates have diverse growth inhibitory effects on osteosarcoma through: (1) activation of apoptosis and inhibition of cell proliferation, (2) inhibition of VEGF-A and VEGFR1 expression by tumor cells, (3) inhibition of tumor-induced angiogenesis, and (4) direct inhibitory actions on endothelial cells. Diphosphonates 15-30 vascular endothelial growth factor A Homo sapiens 179-185 24277524-0 2014 Mutations of the Huntington"s disease protein impact on the ATM-dependent signaling and repair pathways of the radiation-induced DNA double-strand breaks: corrective effect of statins and bisphosphonates. Diphosphonates 188-203 ATM serine/threonine kinase Homo sapiens 60-63 24636958-11 2014 In conclusion, bisphosphonates have diverse growth inhibitory effects on osteosarcoma through: (1) activation of apoptosis and inhibition of cell proliferation, (2) inhibition of VEGF-A and VEGFR1 expression by tumor cells, (3) inhibition of tumor-induced angiogenesis, and (4) direct inhibitory actions on endothelial cells. Diphosphonates 15-30 fms related receptor tyrosine kinase 1 Homo sapiens 190-196 24443409-0 2014 Bisphosphonates inhibit osteosarcoma-mediated osteolysis via attenuation of tumor expression of MCP-1 and RANKL. Diphosphonates 0-15 C-C motif chemokine ligand 2 Homo sapiens 96-101 24443409-0 2014 Bisphosphonates inhibit osteosarcoma-mediated osteolysis via attenuation of tumor expression of MCP-1 and RANKL. Diphosphonates 0-15 TNF superfamily member 11 Homo sapiens 106-111 24277524-9 2014 A combination of biphosphonates and statins complements these impairments by facilitating the nucleo-shuttling of ATM, increasing the yield of recognized and repaired DSB. Diphosphonates 17-31 ATM serine/threonine kinase Homo sapiens 114-117 24357414-1 2014 PURPOSE: The objective of this study was to prepare a bisphosphonate (BP) mediated bone targeting di-PEGylated salmon calcitonin analogue sCT-2(PEG-BP) as a novel bone targeting pharmaceutical. Diphosphonates 54-68 secretin Rattus norvegicus 138-141 24698731-3 2014 However, cells lacking Cx43 also bound BPs. Diphosphonates 39-42 gap junction protein, alpha 1 Rattus norvegicus 23-27 24698731-6 2014 In addition, anti-phospho-tyrosine immunoblot analysis revealed that ALN stimulates tyrosine phosphorylation of several proteins of whole cell lysates, among which the major targets of the BP could be immunochemically identified as Cx43. Diphosphonates 189-191 gap junction protein, alpha 1 Rattus norvegicus 232-236 24698731-9 2014 These results support the hypothesis that BPs bind and inhibit PTPs associated to Cx43 or not, which would lead to the activation of signaling pathways in osteoblasts. Diphosphonates 42-45 gap junction protein, alpha 1 Rattus norvegicus 82-86 24784521-0 2014 CAD/CAM-fabricated telescopic prostheses on periodontally compromised abutments of a patient undergoing intravenous bisphosphonate treatment for osteoporosis: a case report. Diphosphonates 116-130 calmodulin 3 Homo sapiens 4-7 24784521-2 2014 This case report describes how a CAD/CAM-fabricated cobalt-chromium telescopic prosthesis was placed on periodontally compromised abutments of a 74-year-old woman actively undergoing oral and intravenous bisphosphonate treatment for osteoporosis. Diphosphonates 204-218 calmodulin 3 Homo sapiens 37-40 24518563-3 2014 High Ckbb serum level has been found in patients with osteopetrosis and in patients with bisphosphonate (BP)-induced osteopetrosis. Diphosphonates 89-103 creatine kinase B Homo sapiens 5-9 24518563-3 2014 High Ckbb serum level has been found in patients with osteopetrosis and in patients with bisphosphonate (BP)-induced osteopetrosis. Diphosphonates 105-107 creatine kinase B Homo sapiens 5-9 24357414-1 2014 PURPOSE: The objective of this study was to prepare a bisphosphonate (BP) mediated bone targeting di-PEGylated salmon calcitonin analogue sCT-2(PEG-BP) as a novel bone targeting pharmaceutical. Diphosphonates 70-72 secretin Rattus norvegicus 138-141 24772090-8 2014 In particular, preservation of the viability of osteoblasts and osteocytes by the anti-osteoporotic drugs bisphosphonates depends on Cx43 expression in vitro and in vivo, and is mediated by undocked hemichannels. Diphosphonates 106-121 gap junction protein alpha 1 Homo sapiens 133-137 24789335-3 2014 We obtained five structures of T. cruzi SQS and eight structures of human SQS with four classes of inhibitors: the substrate-analog S-thiolo-farnesyl diphosphate, the quinuclidines E5700 and ER119884, several lipophilic bisphosphonates, and the thiocyanate WC-9, with the structures of the two very potent quinuclidines suggesting strategies for selective inhibitor development. Diphosphonates 220-235 farnesyl-diphosphate farnesyltransferase 1 Homo sapiens 74-77 24607589-0 2014 Bisphosphonate prodrugs: synthesis and biological evaluation in HuH7 hepatocarcinoma cells. Diphosphonates 0-14 MIR7-3 host gene Homo sapiens 64-68 24607589-1 2014 We investigated the biological effects of new synthesized bisphosphonates (BPs) on HuH7 hepatocarcinoma cells. Diphosphonates 58-73 MIR7-3 host gene Homo sapiens 83-87 24607589-1 2014 We investigated the biological effects of new synthesized bisphosphonates (BPs) on HuH7 hepatocarcinoma cells. Diphosphonates 75-78 MIR7-3 host gene Homo sapiens 83-87 24607589-2 2014 BPs containing p-bromophenyl (R1 = p-Br, Ph, 2) in their side chain were the more potent to inhibit HuH7 cell viability. Diphosphonates 0-3 MIR7-3 host gene Homo sapiens 100-104 24607589-5 2014 BP analogues inhibited HuH7 cell migration but esterified ones had no effect on invasion due to the hiding of phosphonic groups. Diphosphonates 0-2 MIR7-3 host gene Homo sapiens 23-27 24369118-0 2014 Upregulation of endogenous farnesyl diphosphate synthase overcomes the inhibitory effect of bisphosphonate on protein prenylation in Hela cells. Diphosphonates 92-106 farnesyl diphosphate synthase Homo sapiens 27-56 24389416-13 2014 Further prospective studies are needed to clarify whether the change in FGF-23 and sclerostin levels is a marker or a potential mechanism of the action of BPs at a vascular level. Diphosphonates 155-158 fibroblast growth factor 23 Homo sapiens 72-78 24699741-1 2014 Nitrogen-containing bisphosphonates (N-BPs), such as risedronate and zoledronate, are currently used as a clinical drug for bone-resorption diseases and are potent inhibitors of farnesyl pyrophosphate synthase (FPPS). Diphosphonates 20-35 farnesyl diphosphate synthase Homo sapiens 178-209 24699741-1 2014 Nitrogen-containing bisphosphonates (N-BPs), such as risedronate and zoledronate, are currently used as a clinical drug for bone-resorption diseases and are potent inhibitors of farnesyl pyrophosphate synthase (FPPS). Diphosphonates 20-35 farnesyl diphosphate synthase Homo sapiens 211-215 24287290-1 2014 Recent work has shown that a DBF4 analog in yeast may be a target of nitrogen-containing bisphosphonates. Diphosphonates 89-104 protein serine/threonine kinase activating protein DBF4 Saccharomyces cerevisiae S288C 29-33 24389416-13 2014 Further prospective studies are needed to clarify whether the change in FGF-23 and sclerostin levels is a marker or a potential mechanism of the action of BPs at a vascular level. Diphosphonates 155-158 sclerostin Homo sapiens 83-93 24246954-0 2014 Syntheses and characterization of non-bisphosphonate quinoline derivatives as new FPPS inhibitors. Diphosphonates 38-52 farnesyl diphosphate synthase Homo sapiens 82-86 25032151-0 2014 Platelet-Rich Plasma in Treatment of Zoledronic Acid-Induced Bisphosphonate-related Osteonecrosis of the Jaws. Diphosphonates 61-75 proline rich protein 2-like 1 Rattus norvegicus 0-20 24429286-8 2014 Additionally, LPA1 expression markedly increased in the bone of ovariectomized mice, which was blocked by bisphosphonate treatment. Diphosphonates 106-120 lysophosphatidic acid receptor 1 Mus musculus 14-18 24598749-4 2014 Here, the X-ray crystallographic structures of complexes of FPPS from Leishmania major (the causative agent of cutaneous leishmaniasis) with three bisphosphonates determined at resolutions of 1.8, 1.9 and 2.3 A are reported. Diphosphonates 147-162 farnesyl diphosphate synthase Homo sapiens 60-64 24598749-8 2014 Comparison of the structures of L. major FPPS (LmFPPS) and human FPPS provides new information for the design of bisphosphonates that will be more specific for inhibition of LmFPPS. Diphosphonates 113-128 farnesyl diphosphate synthase Homo sapiens 41-45 24598749-8 2014 Comparison of the structures of L. major FPPS (LmFPPS) and human FPPS provides new information for the design of bisphosphonates that will be more specific for inhibition of LmFPPS. Diphosphonates 113-128 farnesyl diphosphate synthase Homo sapiens 49-53 24598914-3 2014 Crystal structures of hFPPS in ternary complexes with a novel bisphosphonate, YS0470, and the secondary ligands inorganic phosphate (Pi), inorganic pyrophosphate (PPi) and isopentenyl pyrophosphate (IPP) have recently been reported. Diphosphonates 62-76 farnesyl diphosphate synthase Homo sapiens 22-27 24246954-11 2014 GENERAL SIGNIFICANCE: The traditional FPPS active-site inhibitors bisphosphonates show poor membrane permeability to tumor cells, due to their strong polarity. Diphosphonates 66-81 farnesyl diphosphate synthase Homo sapiens 38-42 24528599-4 2014 METHODS: Regulation of DKK-1 by bisphosphonates and statins was assessed in human breast cancer cell lines, and the role of the mevalonate pathway and downstream targets was analyzed. Diphosphonates 32-47 dickkopf WNT signaling pathway inhibitor 1 Homo sapiens 23-28 24301537-0 2014 Early effects of parathyroid hormone on bisphosphonate/steroid-associated compromised osseous wound healing. Diphosphonates 40-54 parathyroid hormone Rattus norvegicus 17-36 24301537-1 2014 SUMMARY: Administration of intermittent parathyroid hormone (PTH) promoted healing of tibial osseous defects and tooth extraction wounds and prevented the development of necrotic lesions in rats on a combined bisphosphonate and steroid regimen. Diphosphonates 209-223 parathyroid hormone Rattus norvegicus 40-59 24528599-6 2014 Clinical relevance was validated by analyzing DKK-1 expression in the tissue and serum of women with breast cancer exposed to bisphosphonates. Diphosphonates 126-141 dickkopf WNT signaling pathway inhibitor 1 Homo sapiens 46-51 24172032-0 2014 Thermodynamic evaluation of the binding of bisphosphonates to human farnesyl pyrophosphate synthase. Diphosphonates 43-58 farnesyl diphosphate synthase Homo sapiens 68-99 24400722-7 2014 CONCLUSION: This patient with a medical history of Crohn"s disease and gastrointestinal remission under Adalimumab therapy presented with osteonecrosis of the jaw after suspended oral and intravenous Bisphosphonate therapy implicating that the biologic therapy with an anti-TNF-alpha antibody might promote the manifestation of osteonecrosis and compromise oral healing capacity. Diphosphonates 200-214 tumor necrosis factor Homo sapiens 274-283 24490900-0 2014 Nitrogen-containing bisphosphonates inhibit RANKL- and M-CSF-induced osteoclast formation through the inhibition of ERK1/2 and Akt activation. Diphosphonates 20-35 tumor necrosis factor (ligand) superfamily, member 11 Mus musculus 44-49 24490900-0 2014 Nitrogen-containing bisphosphonates inhibit RANKL- and M-CSF-induced osteoclast formation through the inhibition of ERK1/2 and Akt activation. Diphosphonates 20-35 colony stimulating factor 1 (macrophage) Mus musculus 55-60 24490900-0 2014 Nitrogen-containing bisphosphonates inhibit RANKL- and M-CSF-induced osteoclast formation through the inhibition of ERK1/2 and Akt activation. Diphosphonates 20-35 mitogen-activated protein kinase 3 Mus musculus 116-122 24490900-0 2014 Nitrogen-containing bisphosphonates inhibit RANKL- and M-CSF-induced osteoclast formation through the inhibition of ERK1/2 and Akt activation. Diphosphonates 20-35 thymoma viral proto-oncogene 1 Mus musculus 127-130 24172032-2 2014 BPs with nitrogen-containing side chains (N-BPs) are known to act as inhibitors for farnesyl pyrophosphate synthase (FPPS), a key enzyme in the mevalonate pathway. Diphosphonates 0-3 farnesyl diphosphate synthase Homo sapiens 84-115 24172032-2 2014 BPs with nitrogen-containing side chains (N-BPs) are known to act as inhibitors for farnesyl pyrophosphate synthase (FPPS), a key enzyme in the mevalonate pathway. Diphosphonates 0-3 farnesyl diphosphate synthase Homo sapiens 117-121 24172032-3 2014 In this study, we evaluated the effect of different side chains on the binding affinity of BPs to human FPPS using calorimetric techniques. Diphosphonates 91-94 farnesyl diphosphate synthase Homo sapiens 104-108 24172032-4 2014 Differential scanning calorimetry (DSC) was used to determine the thermal unfolding of FPPS in the presence of BPs. Diphosphonates 111-114 farnesyl diphosphate synthase Homo sapiens 87-91 24172032-5 2014 The addition of a series of clinically available BPs increased the structural stability of human FPPS by preferential binding, as indicated by an increase in the FPPS unfolding temperature. Diphosphonates 49-52 farnesyl diphosphate synthase Homo sapiens 97-101 24172032-5 2014 The addition of a series of clinically available BPs increased the structural stability of human FPPS by preferential binding, as indicated by an increase in the FPPS unfolding temperature. Diphosphonates 49-52 farnesyl diphosphate synthase Homo sapiens 162-166 24172032-6 2014 The magnitude of the increase was correlated with in vivo antiresorptive efficacy, suggesting that the stabilization of FPPS underlies the inhibitory effect of the BPs. Diphosphonates 164-167 farnesyl diphosphate synthase Homo sapiens 120-124 24172032-7 2014 Isothermal titration calorimetry (ITC) experiments were performed to evaluate the binding thermodynamics of BPs against human FPPS. Diphosphonates 108-111 farnesyl diphosphate synthase Homo sapiens 126-130 24067888-12 2014 Further studies to confirm these results over a longer time frame are warranted together with the possibility to explore the long-term efficacy of a combination of lower anti-TNF doses with bisphosphonates. Diphosphonates 190-205 tumor necrosis factor Homo sapiens 175-178 24186676-1 2014 BACKGROUND: Bisphosphonates may improve implant fixation by inhibition of bone resorption and stimulation of osteoblasts by up regulation of BMP-2. Diphosphonates 12-27 bone morphogenetic protein 2 Homo sapiens 141-146 25002880-6 2014 Treatment with bisphosphonates has led to remission of disease: normalization of ALP values in 90%, documented by the scintigraphy of control. Diphosphonates 15-30 ATHS Homo sapiens 81-84 25365870-1 2014 Bisphosphonates are chemical analogs of isoprene lipids, which competitively decrease the activity of farnesyl diphosphate synthase in osteoclasts and thus retard prenylation. Diphosphonates 0-15 farnesyl diphosphate synthase Homo sapiens 102-131 24373581-7 2014 In HMSC monocultures, the BPs inhibited VEGF expression, but up-regulated the expression of the osteogenic genes alkaline phosphatase (ALP), bone morphogenic protein-2 (BMP-2) and osteocalcin (OC) and, to a greater extent, osteoprotegerin (OPG), a negative regulator of the osteoclastic differentiation, and increased ALP activity. Diphosphonates 26-29 vascular endothelial growth factor A Homo sapiens 40-44 24373581-7 2014 In HMSC monocultures, the BPs inhibited VEGF expression, but up-regulated the expression of the osteogenic genes alkaline phosphatase (ALP), bone morphogenic protein-2 (BMP-2) and osteocalcin (OC) and, to a greater extent, osteoprotegerin (OPG), a negative regulator of the osteoclastic differentiation, and increased ALP activity. Diphosphonates 26-29 alkaline phosphatase, placental Homo sapiens 113-133 24373581-7 2014 In HMSC monocultures, the BPs inhibited VEGF expression, but up-regulated the expression of the osteogenic genes alkaline phosphatase (ALP), bone morphogenic protein-2 (BMP-2) and osteocalcin (OC) and, to a greater extent, osteoprotegerin (OPG), a negative regulator of the osteoclastic differentiation, and increased ALP activity. Diphosphonates 26-29 alkaline phosphatase, placental Homo sapiens 135-138 24373581-7 2014 In HMSC monocultures, the BPs inhibited VEGF expression, but up-regulated the expression of the osteogenic genes alkaline phosphatase (ALP), bone morphogenic protein-2 (BMP-2) and osteocalcin (OC) and, to a greater extent, osteoprotegerin (OPG), a negative regulator of the osteoclastic differentiation, and increased ALP activity. Diphosphonates 26-29 bone morphogenetic protein 2 Homo sapiens 141-167 24373581-7 2014 In HMSC monocultures, the BPs inhibited VEGF expression, but up-regulated the expression of the osteogenic genes alkaline phosphatase (ALP), bone morphogenic protein-2 (BMP-2) and osteocalcin (OC) and, to a greater extent, osteoprotegerin (OPG), a negative regulator of the osteoclastic differentiation, and increased ALP activity. Diphosphonates 26-29 bone morphogenetic protein 2 Homo sapiens 169-174 24373581-7 2014 In HMSC monocultures, the BPs inhibited VEGF expression, but up-regulated the expression of the osteogenic genes alkaline phosphatase (ALP), bone morphogenic protein-2 (BMP-2) and osteocalcin (OC) and, to a greater extent, osteoprotegerin (OPG), a negative regulator of the osteoclastic differentiation, and increased ALP activity. Diphosphonates 26-29 bone gamma-carboxyglutamate protein Homo sapiens 180-191 24373581-7 2014 In HMSC monocultures, the BPs inhibited VEGF expression, but up-regulated the expression of the osteogenic genes alkaline phosphatase (ALP), bone morphogenic protein-2 (BMP-2) and osteocalcin (OC) and, to a greater extent, osteoprotegerin (OPG), a negative regulator of the osteoclastic differentiation, and increased ALP activity. Diphosphonates 26-29 TNF receptor superfamily member 11b Homo sapiens 223-238 24373581-7 2014 In HMSC monocultures, the BPs inhibited VEGF expression, but up-regulated the expression of the osteogenic genes alkaline phosphatase (ALP), bone morphogenic protein-2 (BMP-2) and osteocalcin (OC) and, to a greater extent, osteoprotegerin (OPG), a negative regulator of the osteoclastic differentiation, and increased ALP activity. Diphosphonates 26-29 TNF receptor superfamily member 11b Homo sapiens 240-243 24373581-7 2014 In HMSC monocultures, the BPs inhibited VEGF expression, but up-regulated the expression of the osteogenic genes alkaline phosphatase (ALP), bone morphogenic protein-2 (BMP-2) and osteocalcin (OC) and, to a greater extent, osteoprotegerin (OPG), a negative regulator of the osteoclastic differentiation, and increased ALP activity. Diphosphonates 26-29 alkaline phosphatase, placental Homo sapiens 318-321 24724423-8 2014 BP induced the apoptosis of THP-1. Diphosphonates 0-2 GLI family zinc finger 2 Homo sapiens 28-33 24399185-9 2013 The WNT-pathway and in particular its antagonists SCL and DKK1 seems to play a key role in the regulation of bone remodeling during treatment with bone active agents such as bisphosphonates, but not only. Diphosphonates 174-189 dickkopf WNT signaling pathway inhibitor 1 Homo sapiens 58-62 24241351-0 2013 A new bisphosphonate derivative, CP, induces gastric cancer cell apoptosis via activation of the ERK1/2 signaling pathway. Diphosphonates 6-20 mitogen-activated protein kinase 3 Homo sapiens 97-103 22901640-2 2013 A new alternative class of agents, receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitors, are now available for use in these indications and have the potential to replace intravenous BPs. Diphosphonates 200-203 TNF superfamily member 11 Homo sapiens 35-86 24366804-6 2013 Two patients responded to oral bisphosphonate treatment and achieved normalised ALP levels and pain relief. Diphosphonates 31-45 alkaline phosphatase, placental Homo sapiens 80-83 22901640-2 2013 A new alternative class of agents, receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitors, are now available for use in these indications and have the potential to replace intravenous BPs. Diphosphonates 200-203 TNF superfamily member 11 Homo sapiens 88-93 23962725-9 2013 This was supported by the finding that gene expression of the anti-apoptotic genes Bcl-2 and Bcl-xL was higher in jaw cells than long bone cells, suggesting that the jaw cells might be more resistant to BP-induced apoptosis. Diphosphonates 203-205 B cell leukemia/lymphoma 2 Mus musculus 83-88 24071448-3 2013 In an attempt to devise new approaches to selective inhibitor derivatives, we describe novel bisphosphonate bone seeking MMP inhibitors (BP-MMPIs), capable to be selectively targeted and to overcome undesired side effects of broad spectrum MMPIs. Diphosphonates 93-107 matrix metallopeptidase 2 Mus musculus 121-124 24370033-1 2013 This study was aimed to investigate the effect of bortezomib combined with bisphosphonates on serum levels of DKK-1 and RANKL in multiple myeloma patients, and to evaluate its role in the therapy of osteolytic lesion. Diphosphonates 75-90 dickkopf WNT signaling pathway inhibitor 1 Homo sapiens 110-115 24370033-1 2013 This study was aimed to investigate the effect of bortezomib combined with bisphosphonates on serum levels of DKK-1 and RANKL in multiple myeloma patients, and to evaluate its role in the therapy of osteolytic lesion. Diphosphonates 75-90 TNF superfamily member 11 Homo sapiens 120-125 24370033-7 2013 It is concluded that bortezomib combined with bisphosphonates obviously reduce the serum levels of DKK-1 and RANKL, thus has beneficial effect on osteolytic lesion. Diphosphonates 46-61 dickkopf WNT signaling pathway inhibitor 1 Homo sapiens 99-104 24370033-7 2013 It is concluded that bortezomib combined with bisphosphonates obviously reduce the serum levels of DKK-1 and RANKL, thus has beneficial effect on osteolytic lesion. Diphosphonates 46-61 TNF superfamily member 11 Homo sapiens 109-114 23954759-9 2013 Among BRONJ patients who discontinued BP, in a linear mixed model, only CTX showed a significant increase over time (beta=0.002, P=0.007). Diphosphonates 38-40 cytochrome P450 family 27 subfamily A member 1 Homo sapiens 72-75 23962725-9 2013 This was supported by the finding that gene expression of the anti-apoptotic genes Bcl-2 and Bcl-xL was higher in jaw cells than long bone cells, suggesting that the jaw cells might be more resistant to BP-induced apoptosis. Diphosphonates 203-205 BCL2-like 1 Mus musculus 93-99 24012179-4 2013 Based on molecular docking results, the binding modes of the macrocyclic bisphosphonates in the active centre of PTP1B are discussed. Diphosphonates 73-88 protein tyrosine phosphatase non-receptor type 1 Homo sapiens 113-118 24353873-11 2013 The bisphosphonate group showed the same level of TRAP positive cell count, osteocalcin and angiopoietin 1 as the control group. Diphosphonates 4-18 tudor domain containing 7 Rattus norvegicus 50-54 24353873-11 2013 The bisphosphonate group showed the same level of TRAP positive cell count, osteocalcin and angiopoietin 1 as the control group. Diphosphonates 4-18 bone gamma-carboxyglutamate protein Rattus norvegicus 76-87 24353873-11 2013 The bisphosphonate group showed the same level of TRAP positive cell count, osteocalcin and angiopoietin 1 as the control group. Diphosphonates 4-18 angiopoietin 1 Rattus norvegicus 92-106 23746422-0 2013 The effects of adjunctive parathyroid hormone injection on bisphosphonate-related osteonecrosis of the jaws: an animal study. Diphosphonates 59-73 parathyroid hormone Homo sapiens 26-45 23522850-2 2013 We investigated how the chronic application of bisphosphonate affects the RANKL and OPG levels in an animal model and whether this effect may be related to bisphosphonate-related osteonecrosis of the jaws (BRONJ). Diphosphonates 47-61 TNF superfamily member 11 Rattus norvegicus 74-79 23919676-1 2013 Bisphosphonates are potent inhibitors of farnesyl pyrophosphate synthase (FPPS) and geranylgeranyl diphosphate synthase (GGPPS). Diphosphonates 0-15 farnesyl diphosphate synthase Homo sapiens 41-72 23919676-1 2013 Bisphosphonates are potent inhibitors of farnesyl pyrophosphate synthase (FPPS) and geranylgeranyl diphosphate synthase (GGPPS). Diphosphonates 0-15 farnesyl diphosphate synthase Homo sapiens 74-78 23919676-1 2013 Bisphosphonates are potent inhibitors of farnesyl pyrophosphate synthase (FPPS) and geranylgeranyl diphosphate synthase (GGPPS). Diphosphonates 0-15 geranylgeranyl diphosphate synthase 1 Homo sapiens 84-119 23919676-1 2013 Bisphosphonates are potent inhibitors of farnesyl pyrophosphate synthase (FPPS) and geranylgeranyl diphosphate synthase (GGPPS). Diphosphonates 0-15 geranylgeranyl diphosphate synthase 1 Homo sapiens 121-126 23947433-0 2013 Bisphosphonate-linked hyaluronic acid hydrogel sequesters and enzymatically releases active bone morphogenetic protein-2 for induction of osteogenic differentiation. Diphosphonates 0-14 bone morphogenetic protein 2 Homo sapiens 92-120 23947433-4 2013 Herein we demonstrate that functionalization of a hyaluronan (HA) hydrogel with covalently linked bisphosphonate (BP) ligands provides efficient sequestering of BMP-2 in the resulting HA-BP hydrogel. Diphosphonates 98-112 bone morphogenetic protein 2 Homo sapiens 161-166 23947433-4 2013 Herein we demonstrate that functionalization of a hyaluronan (HA) hydrogel with covalently linked bisphosphonate (BP) ligands provides efficient sequestering of BMP-2 in the resulting HA-BP hydrogel. Diphosphonates 114-116 bone morphogenetic protein 2 Homo sapiens 161-166 23522850-2 2013 We investigated how the chronic application of bisphosphonate affects the RANKL and OPG levels in an animal model and whether this effect may be related to bisphosphonate-related osteonecrosis of the jaws (BRONJ). Diphosphonates 47-61 TNF receptor superfamily member 11B Rattus norvegicus 84-87 23898082-6 2013 The administration of apigenin in combined treatment with bisphosphonates and IR showed: a decrease in the cytotoxic effect on TRAMP-C1 and B16F10 cells in the treatment with ibandronate; a protective effect on normal PNT2 and melanoma cells, but not on TRAMP-C1 cells in the treatment with zoledronic acid; and provided protection only to PNT2 cells in the treatment with pamidronate. Diphosphonates 58-73 translocating chain-associating membrane protein 1 Mus musculus 127-132 23604689-2 2013 Bisphosphonates substantially reduce osteocalcin levels. Diphosphonates 0-15 bone gamma-carboxyglutamate protein Homo sapiens 37-48 23752163-3 2013 We report the successful use of bisphosphonate treatment (zoledronic acid) in an 8-year-old boy who presented with an ABC that did not respond to embolization. Diphosphonates 32-46 ATP binding cassette subfamily B member 6 (Langereis blood group) Homo sapiens 118-121 23748710-7 2013 SOST expression is increased with advancing age, by glucocorticoid treatment and during treatment with antiresorptive agents such as bisphosphonates and denosumab, while it is decreased by parathyroid hormone excess or administration of estrogens. Diphosphonates 133-148 sclerostin Homo sapiens 0-4 23794630-1 2013 The potent nitrogen-containing bisphosphonate zoledronate inhibits farnesyl pyrophosphate synthase, a key enzyme of the mevalonate pathway that is often hyperactive in malignant cells. Diphosphonates 31-45 farnesyl diphosphate synthase Homo sapiens 67-98 23607938-6 2013 It also activated ERK, sensitized spiral ganglion cells (SGC) to apoptosis, and inhibited proliferation and survival of cochlear stem cells in vitro, which could be rescued by treatment with exogenous OPG, an ERK inhibitor, or bisphosphonate. Diphosphonates 227-241 TNF receptor superfamily member 11b Homo sapiens 201-204 23607938-6 2013 It also activated ERK, sensitized spiral ganglion cells (SGC) to apoptosis, and inhibited proliferation and survival of cochlear stem cells in vitro, which could be rescued by treatment with exogenous OPG, an ERK inhibitor, or bisphosphonate. Diphosphonates 227-241 mitogen-activated protein kinase 1 Homo sapiens 209-212 23461552-6 2013 Moreover, the ratio of Foxp3-positive regulatory T-cells (Tregs) in peripheral blood decreased, and interleukin (IL)-17 increased in the serum of BP-treated minipigs. Diphosphonates 146-148 forkhead box P3 Sus scrofa 23-28 23461552-6 2013 Moreover, the ratio of Foxp3-positive regulatory T-cells (Tregs) in peripheral blood decreased, and interleukin (IL)-17 increased in the serum of BP-treated minipigs. Diphosphonates 146-148 interleukin-17A Sus scrofa 100-119 23807419-11 2013 In addition, both BPs strongly influenced the secretion of the chemokine CCL2 by osteoblasts. Diphosphonates 18-21 C-C motif chemokine ligand 2 Homo sapiens 73-77 23572387-0 2013 Basic fibroblast growth factor attenuates bisphosphonate-induced oxidative injury but decreases zinc and copper levels in oral epithelium of rat. Diphosphonates 42-56 fibroblast growth factor 2 Rattus norvegicus 0-30 23564016-1 2013 Nitrogen-containing bisphosphonates have been well known to be inhibited farnesyl diphosphate synthase (FDPS), an enzyme in mevalonic acid metabolism, resulting in disturbance in polymerization of cytoskeleton structure in bone resorption and promotion of apoptosis in mature osteoclasts. Diphosphonates 20-35 farnesyl diphosphate synthetase Mus musculus 73-102 23564016-1 2013 Nitrogen-containing bisphosphonates have been well known to be inhibited farnesyl diphosphate synthase (FDPS), an enzyme in mevalonic acid metabolism, resulting in disturbance in polymerization of cytoskeleton structure in bone resorption and promotion of apoptosis in mature osteoclasts. Diphosphonates 20-35 farnesyl diphosphate synthetase Mus musculus 104-108 23564016-12 2013 These results suggest that nitrogen-containing bisphosphonates suppress the activity of osteoclastic acid-activated Cl(-) currents through FDPS inhibition, suggesting the inhibition of Cl(-) extrusion activity. Diphosphonates 47-62 farnesyl diphosphate synthetase Mus musculus 139-143 26909280-3 2013 Bisphosphonates are thought to have an anti-angiogenic activity as decreased levels of VEGF have been reported in some, although not all patients, following treatment with bisphosphonates. Diphosphonates 0-15 vascular endothelial growth factor A Homo sapiens 87-91 26909280-3 2013 Bisphosphonates are thought to have an anti-angiogenic activity as decreased levels of VEGF have been reported in some, although not all patients, following treatment with bisphosphonates. Diphosphonates 172-187 vascular endothelial growth factor A Homo sapiens 87-91 23616636-0 2013 IL-17-mediated M1/M2 macrophage alteration contributes to pathogenesis of bisphosphonate-related osteonecrosis of the jaws. Diphosphonates 74-88 interleukin 17A Mus musculus 0-5 23572387-2 2013 The bFGF may modulate the BP-induced oxidative stress in oral epithelium of rats. Diphosphonates 26-28 fibroblast growth factor 2 Rattus norvegicus 4-8 23572387-3 2013 This study was undertaken to explore possible beneficial antioxidant effects of bFGF on oxidative stress induced by BP in oral epithelium of rats. Diphosphonates 116-118 fibroblast growth factor 2 Rattus norvegicus 80-84 23572387-12 2013 In conclusion, treatment with bFGF modulated the antioxidant redox system and reduced the oral epithelium oxidative stress induced by BP. Diphosphonates 134-136 fibroblast growth factor 2 Rattus norvegicus 30-34 23503790-1 2013 The bone anabolic effect of parathyroid hormone (PTH) therapy is blunted when used in patients who were previously on bisphosphonate treatment. Diphosphonates 118-132 parathyroid hormone Homo sapiens 28-47 23421555-2 2013 Here, we used this approach combined with similarity searches and experimental inhibition assays to identify several low micromolar, non-bisphosphonate inhibitors, bisamidines, of farnesyl diphosphate synthase (FPPS), an enzyme targeted by some anticancer and antimicrobial agents and for the treatment of bone resorption diseases. Diphosphonates 137-151 farnesyl diphosphate synthase Homo sapiens 180-209 23421555-3 2013 This novel class of farnesyl diphosphate synthase inhibitors have more drug-like properties than existing bisphosphonate inhibitors, making them interesting pharmaceutical leads. Diphosphonates 106-120 farnesyl diphosphate synthase Homo sapiens 20-49 23138352-1 2013 This study was performed to investigate the effects of the co-administration of proton pump inhibitor (PPI) on the efficacy of bisphosphonate (BP) treatment for osteoporosis. Diphosphonates 127-141 ATPase H+/K+ transporting subunit alpha Homo sapiens 80-91 23536322-8 2013 (1)H and (31)P NMR studies in aqueous solution performed on NaK-Ni7-Ale2 and Ni7-(AleNapht)2 evidenced that the PW9/Ni7/bisphosphonate assembly is stable in solution. Diphosphonates 120-134 TANK binding kinase 1 Homo sapiens 60-63 23404413-9 2013 RESULTS: We found a higher concentration of tumour necrosis factor alpha (TNF-alpha) three weeks after surgery in rats implanted with BP-enriched cement compared with rats implanted with clean cement. Diphosphonates 134-136 tumor necrosis factor Rattus norvegicus 74-83 23404413-10 2013 After six weeks of treatment, TNF-alpha levels decreased significantly in rats treated with BP-enriched cement, whereas the control group experienced an increase in TNF-alpha. Diphosphonates 92-94 tumor necrosis factor Rattus norvegicus 30-39 23404413-11 2013 The concentration of osteoprotegerin ligand (OPG) was higher in rats with BP implants. Diphosphonates 74-76 TNF superfamily member 11 Rattus norvegicus 21-43 23404413-11 2013 The concentration of osteoprotegerin ligand (OPG) was higher in rats with BP implants. Diphosphonates 74-76 TNF superfamily member 11 Rattus norvegicus 45-48 23404413-13 2013 CONCLUSIONS: We conclude that use of bisphosphonate (Pamifos ), which is present in bone cement, has an effect on bone turnover in that BPs stimulate an increase in OPG and a decrease in RANKL in the bone microenvironment and thus may be an important component of mechanisms that reduce bone resorption. Diphosphonates 37-51 TNF superfamily member 11 Rattus norvegicus 165-168 23404413-13 2013 CONCLUSIONS: We conclude that use of bisphosphonate (Pamifos ), which is present in bone cement, has an effect on bone turnover in that BPs stimulate an increase in OPG and a decrease in RANKL in the bone microenvironment and thus may be an important component of mechanisms that reduce bone resorption. Diphosphonates 37-51 TNF superfamily member 11 Rattus norvegicus 187-192 23404413-13 2013 CONCLUSIONS: We conclude that use of bisphosphonate (Pamifos ), which is present in bone cement, has an effect on bone turnover in that BPs stimulate an increase in OPG and a decrease in RANKL in the bone microenvironment and thus may be an important component of mechanisms that reduce bone resorption. Diphosphonates 136-139 TNF superfamily member 11 Rattus norvegicus 165-168 23404413-13 2013 CONCLUSIONS: We conclude that use of bisphosphonate (Pamifos ), which is present in bone cement, has an effect on bone turnover in that BPs stimulate an increase in OPG and a decrease in RANKL in the bone microenvironment and thus may be an important component of mechanisms that reduce bone resorption. Diphosphonates 136-139 TNF superfamily member 11 Rattus norvegicus 187-192 23610597-1 2013 We synthesized 30 lipophilic bisphosphonates and tested them in malaria parasite killing (targeting parasite geranylgeranyl diphosphate synthase, GGPPS) as well in human gammadelta T cell activation (targeting human farnesyl diphosphate synthase, FPPS). Diphosphonates 29-44 geranylgeranyl diphosphate synthase 1 Homo sapiens 146-151 23610597-1 2013 We synthesized 30 lipophilic bisphosphonates and tested them in malaria parasite killing (targeting parasite geranylgeranyl diphosphate synthase, GGPPS) as well in human gammadelta T cell activation (targeting human farnesyl diphosphate synthase, FPPS). Diphosphonates 29-44 farnesyl diphosphate synthase Homo sapiens 247-251 23381659-0 2013 Sphingosine-1-phosphate protects against bisphosphonate-induced HUVEC cell death via regulation of c-Jun-N-terminal kinase signaling. Diphosphonates 41-55 mitogen-activated protein kinase 8 Homo sapiens 99-122 23381659-7 2013 S1P blocked BP-induced caspase-3 activation, nuclear factor-kappaB activation, c-Jun-N-terminal kinase (JNK) phosphorylation and DNA fragmentation. Diphosphonates 12-14 caspase 3 Homo sapiens 23-32 23381659-7 2013 S1P blocked BP-induced caspase-3 activation, nuclear factor-kappaB activation, c-Jun-N-terminal kinase (JNK) phosphorylation and DNA fragmentation. Diphosphonates 12-14 mitogen-activated protein kinase 8 Homo sapiens 79-102 23381659-7 2013 S1P blocked BP-induced caspase-3 activation, nuclear factor-kappaB activation, c-Jun-N-terminal kinase (JNK) phosphorylation and DNA fragmentation. Diphosphonates 12-14 mitogen-activated protein kinase 8 Homo sapiens 104-107 23381659-8 2013 The blocking of JNK phosphorylation inhibited BP-induced caspase activation and HUVEC cell death. Diphosphonates 46-48 mitogen-activated protein kinase 8 Homo sapiens 16-19 23381659-9 2013 The present study demonstrates that S1P inhibits BP-induced endothelial cell death via regulation of JNK phosphorylation, and also suggests that S1P has the potential to be a therapeutic drug in various vascular diseases induced by BP. Diphosphonates 49-51 mitogen-activated protein kinase 8 Homo sapiens 101-104 23376077-2 2013 In addition to inhibiting osteoclast function, bisphosphonates have been reported to also promote survival of osteocyte and osteoblast via an anti-apoptotic effect, mediated by opening of hemi-gap junction channels formed by connexin43 (Cx43). Diphosphonates 47-62 gap junction protein alpha 1 Homo sapiens 225-235 23376077-2 2013 In addition to inhibiting osteoclast function, bisphosphonates have been reported to also promote survival of osteocyte and osteoblast via an anti-apoptotic effect, mediated by opening of hemi-gap junction channels formed by connexin43 (Cx43). Diphosphonates 47-62 gap junction protein alpha 1 Homo sapiens 237-241 22821192-9 2013 RESULTS: From 2002 to 2008, dispensed prescriptions of bisphosphonates in Spain increased from 3.28 to 17.66 DDD/1,000 inhabitants per day. Diphosphonates 55-70 keratin 5 Homo sapiens 109-114 22864527-6 2013 CONCLUSIONS: Our results suggest that mucosa, stimulated by bisphosphonate released from the bone, can contribute to the development of jaw necrosis, reducing VEGF, and producing IL-6 in consequence of hydroxymethylglutaryl coenzyme A reductase reduction. Diphosphonates 60-74 vascular endothelial growth factor A Homo sapiens 159-163 22864527-6 2013 CONCLUSIONS: Our results suggest that mucosa, stimulated by bisphosphonate released from the bone, can contribute to the development of jaw necrosis, reducing VEGF, and producing IL-6 in consequence of hydroxymethylglutaryl coenzyme A reductase reduction. Diphosphonates 60-74 interleukin 6 Homo sapiens 179-183 22864527-8 2013 CLINICAL RELEVANCE: The results of this study suggest the importance of evaluating during bisphosphonate treatment the production of IL-6, RANKL, osteoprotegerin, and VEGF, in order to monitor the jaw osteonecrosis onset. Diphosphonates 90-104 interleukin 6 Homo sapiens 133-137 24524054-1 2013 BACKGROUND: Bisphosphonate is used in osteoporosis treatment to repress osteoclast activity, which then decreases levels of osteocalcin (OC). Diphosphonates 12-26 bone gamma-carboxyglutamate protein Homo sapiens 124-135 23275389-9 2013 There was a significant difference in the change of SASSS in patients treated with both TNF inhibitors and bisphosphonates compared with those treated with TNF inhibitors alone (P < 0.01). Diphosphonates 107-122 tumor necrosis factor Homo sapiens 156-159 23138352-1 2013 This study was performed to investigate the effects of the co-administration of proton pump inhibitor (PPI) on the efficacy of bisphosphonate (BP) treatment for osteoporosis. Diphosphonates 143-145 ATPase H+/K+ transporting subunit alpha Homo sapiens 80-91 23412516-0 2013 Activated protein C differentially regulates both viability and differentiation of osteoblasts mediated by bisphosphonates. Diphosphonates 107-122 APC regulator of WNT signaling pathway Homo sapiens 0-19 23410546-10 2013 Multivariate analysis revealed that increased ApoB/ApoA-I ratio (odds ratio [OR]: 1.41, 95% confidence interval [CI]: 1.10 to 1.82 per 0.1 increment; p = 0.007) and the use of bisphosphonates (OR: 3.57, 95% CI: 1.14 to 10.80 p = 0.02) were the strongest independent predictors of SVD. Diphosphonates 176-191 apolipoprotein B Homo sapiens 46-50 23228448-2 2013 Here, foscarnet, an antiviral drug which inhibits several viral DNA polymerases by mimic pyrophosphate of nucleotides, was identified to interact with fibroblast growth factor 2 and stabilize the growth factor against tryptic digestion similar like the non-nitrogen containing bisphosphonates clodronate and etidronate that we have reported just recently as inhibitors of FGF-induced cell proliferation. Diphosphonates 277-292 fibroblast growth factor 2 Homo sapiens 151-177 23171856-0 2013 Association between CYP2C8 (rs1934951) polymorphism and bisphosphonate-related osteonecrosis of the jaws in patients on bisphosphonate therapy: a meta-analysis. Diphosphonates 56-70 cytochrome P450 family 2 subfamily C member 8 Homo sapiens 20-26 23160629-7 2013 Bisphosphonate injections in Ank (+/+) mice replicate the Ank (KI/KI) incisor phenotype. Diphosphonates 0-14 progressive ankylosis Mus musculus 29-32 23160629-7 2013 Bisphosphonate injections in Ank (+/+) mice replicate the Ank (KI/KI) incisor phenotype. Diphosphonates 0-14 progressive ankylosis Mus musculus 74-77 23138882-11 2013 Seven of 17 patients required readministration of oral bisphosphonate (risedronate, six; alendronate, one) due to elevated total ALP at 27 months (mean ranging from 9 to 39 months) after the initial administration of risedronate. Diphosphonates 55-69 alkaline phosphatase, placental Homo sapiens 129-132 26909267-11 2013 This large, retrospective study demonstrates a significant survival benefit with adjuvant bisphosphonates in patients with early breast cancer, particularly in patients with node-positive and hormone receptor-positive disease. Diphosphonates 90-105 nuclear receptor subfamily 4 group A member 1 Homo sapiens 192-208 22842101-4 2013 Recent studies have validated FPPS as a molecular target of bisphosphonates for drug development against tumors as well as human pathogens. Diphosphonates 60-75 farnesyl diphosphate synthase Homo sapiens 30-34 23085435-0 2013 Nitrogen-containing bisphosphonates induce apoptosis of hematopoietic tumor cells via inhibition of Ras signaling pathways and Bim-mediated activation of the intrinsic apoptotic pathway. Diphosphonates 20-35 BCL2 like 11 Homo sapiens 127-130 23257899-0 2013 Endo180 modulation by bisphosphonates and diagnostic accuracy in metastatic breast cancer. Diphosphonates 22-37 mannose receptor C type 2 Homo sapiens 0-7 23257899-3 2013 METHODS: Endo180 was quantified in BCa cell conditioned medium and plasma from BCa patients stratified according to disease status and bisphosphonate treatment (n=88). Diphosphonates 135-149 mannose receptor C type 2 Homo sapiens 9-16 23257899-8 2013 Bisphosphonate treatment was associated with reduced Endo180 levels in BCa patients with bone metastasis (P=0.011; n=42). Diphosphonates 0-14 mannose receptor C type 2 Homo sapiens 53-60 23257899-9 2013 True/false-positive rates in bisphosphonate-naive patients (n=57) were: 68%/45% for CA 15-3 antigen; <=95%/>=20% for Endo180; and <=92%/>=21% for CA 15-3 antigen+Endo180. Diphosphonates 29-43 mucin 1, cell surface associated Homo sapiens 84-91 23257899-9 2013 True/false-positive rates in bisphosphonate-naive patients (n=57) were: 68%/45% for CA 15-3 antigen; <=95%/>=20% for Endo180; and <=92%/>=21% for CA 15-3 antigen+Endo180. Diphosphonates 29-43 mannose receptor C type 2 Homo sapiens 123-130 23257899-10 2013 CONCLUSION: Endo180 is a potential marker modulated by bisphosphonates in metastatic BCa. Diphosphonates 55-70 mannose receptor C type 2 Homo sapiens 12-19 23171856-0 2013 Association between CYP2C8 (rs1934951) polymorphism and bisphosphonate-related osteonecrosis of the jaws in patients on bisphosphonate therapy: a meta-analysis. Diphosphonates 120-134 cytochrome P450 family 2 subfamily C member 8 Homo sapiens 20-26 23687446-1 2013 PURPOSE: To investigate the anchoring of plasmid DNA/anti-DNA antibody/cationic lipid tri-complex (DAC micelles) onto bisphosphonate-modified 316 L coronary stents for cardiovascular site-specific gene delivery. Diphosphonates 118-132 arylacetamide deacetylase Homo sapiens 99-102 23867803-3 2013 In addition we evaluated the potencies of bisphosphonate, which was previously reported to suppress the expression of matrix metalloproteinase 9 (MMP-9), as a supportive therapy for AS together with docetaxel in 6 cases of cutaneous AS. Diphosphonates 42-56 matrix metallopeptidase 9 Homo sapiens 118-144 23867803-3 2013 In addition we evaluated the potencies of bisphosphonate, which was previously reported to suppress the expression of matrix metalloproteinase 9 (MMP-9), as a supportive therapy for AS together with docetaxel in 6 cases of cutaneous AS. Diphosphonates 42-56 matrix metallopeptidase 9 Homo sapiens 146-151 22996291-2 2013 Zoledronic acid (ZA) is a bisphosphonate known to upregulate the expression of TRAIL on human gammadelta T cells. Diphosphonates 26-40 TNF superfamily member 10 Homo sapiens 79-84 22763138-0 2013 Parathyroid hormone may be a promising therapy for bisphosphonate-related osteonecrosis of jaw bones. Diphosphonates 51-65 parathyroid hormone Homo sapiens 0-19 23392871-3 2013 Recently, bisphosphonates, antiosteoporosis drugs, have been reported to have anti-angiogenic effect by decreasing VEGF. Diphosphonates 10-25 vascular endothelial growth factor A Homo sapiens 115-119 23234314-2 2012 Bisphosphonate inhibitors of human FPPS are valuable therapeutics for the treatment of bone-resorption disorders and have also demonstrated efficacy in multiple tumor types. Diphosphonates 0-14 farnesyl diphosphate synthase Homo sapiens 35-39 23920073-3 2013 This paper examines the effectiveness of CTX as a biochemical marker for BRONJ and its utility to the dentist in establishing appropriate treatment plans for patients with a history of bisphosphonate use. Diphosphonates 185-199 cytochrome P450 family 27 subfamily A member 1 Homo sapiens 41-44 23920073-4 2013 Alternative means of assessing the risk of BRONJ are discussed, and 2 case vignettes are presented to demonstrate dental treatment planning for patients with a history of bisphosphonate use, in the context of specific CTX results. Diphosphonates 171-185 cytochrome P450 family 27 subfamily A member 1 Homo sapiens 218-221 23533771-4 2013 In addition, the nitrogen-containing BPs (N-BPs), second-generation BPs, act by inhibiting farnesyl diphosphate (FPP) synthase, a key enzyme of the mevalonate pathway. Diphosphonates 37-40 farnesyl diphosphate synthase Homo sapiens 91-126 23533771-4 2013 In addition, the nitrogen-containing BPs (N-BPs), second-generation BPs, act by inhibiting farnesyl diphosphate (FPP) synthase, a key enzyme of the mevalonate pathway. Diphosphonates 44-47 farnesyl diphosphate synthase Homo sapiens 91-126 23212591-3 2013 The widely-used bisphosphonates or the new therapeutic option, denosumab an inhibitor of the receptor activator of NF-kappaB ligand (RANKL), interrupt this vicious cycle, inhibit tumor growth, and in clinical practice prevent skeleton-related events. Diphosphonates 16-31 TNF superfamily member 11 Homo sapiens 93-131 23212591-3 2013 The widely-used bisphosphonates or the new therapeutic option, denosumab an inhibitor of the receptor activator of NF-kappaB ligand (RANKL), interrupt this vicious cycle, inhibit tumor growth, and in clinical practice prevent skeleton-related events. Diphosphonates 16-31 TNF superfamily member 11 Homo sapiens 133-138 24209445-8 2013 The identification of SLC20A2, PDGFRB, and PDGFB provides a new avenue for potential treatments based on compounds such as bisphosphonates and those modulating the PDGFB pathway. Diphosphonates 123-138 solute carrier family 20 member 2 Homo sapiens 22-29 24209445-8 2013 The identification of SLC20A2, PDGFRB, and PDGFB provides a new avenue for potential treatments based on compounds such as bisphosphonates and those modulating the PDGFB pathway. Diphosphonates 123-138 platelet derived growth factor receptor beta Homo sapiens 31-37 24209445-8 2013 The identification of SLC20A2, PDGFRB, and PDGFB provides a new avenue for potential treatments based on compounds such as bisphosphonates and those modulating the PDGFB pathway. Diphosphonates 123-138 platelet derived growth factor subunit B Homo sapiens 43-48 22959779-0 2013 Comparison of serum Dkk1 (Dickkopf-1) and bone mineral density in patients on bisphosphonate treatment vs no treatment. Diphosphonates 78-92 dickkopf WNT signaling pathway inhibitor 1 Homo sapiens 20-24 22959779-6 2013 This study demonstrates the effect of bisphosphonates on Dkk1 levels and its correlation with bone mineral density (BMD). Diphosphonates 38-53 dickkopf WNT signaling pathway inhibitor 1 Homo sapiens 57-61 22959779-10 2013 Hence, bisphosphonate therapy leads to reduction in Dkk1 levels, but it does not correlate with BMD in such patients. Diphosphonates 7-21 dickkopf WNT signaling pathway inhibitor 1 Homo sapiens 52-56 23234314-3 2012 Inhibition of human FPPS by bisphosphonates in vivo is thought to involve closing of the enzyme"s C-terminal tail induced by the binding of the second substrate isopentenyl pyrophosphate (IPP). Diphosphonates 28-43 farnesyl diphosphate synthase Homo sapiens 20-24 23234314-5 2012 The crystal structure of human FPPS in complex with a novel bisphosphonate YS0470 and in the absence of a second substrate showed partial ordering of the tail in the closed conformation. Diphosphonates 60-74 farnesyl diphosphate synthase Homo sapiens 31-35 23227959-1 2012 BACKGROUND: The aim of the present study was to assess whether the efficacy of bisphosphonate treatment is influenced by PTH levels measured in newly diagnosed osteoporotic patients and to identify the threshold value, beyond which PTH level negatively influences therapeutic efficacy. Diphosphonates 79-93 parathyroid hormone Homo sapiens 121-124 23227959-1 2012 BACKGROUND: The aim of the present study was to assess whether the efficacy of bisphosphonate treatment is influenced by PTH levels measured in newly diagnosed osteoporotic patients and to identify the threshold value, beyond which PTH level negatively influences therapeutic efficacy. Diphosphonates 79-93 parathyroid hormone Homo sapiens 232-235 23227959-11 2012 CONCLUSION: Our findings imply that a baseline PTH level over 60 ng/mL can reduce the efficacy of bisphosphonate treatment. Diphosphonates 98-112 parathyroid hormone Homo sapiens 47-50 23123579-1 2012 AIM: Bisphosphonates increase bone mineral density (BMD) and also increase parathyroid hormone (PTH): the rule of increased PTH on BMD is not well known. Diphosphonates 5-20 parathyroid hormone Homo sapiens 75-94 22676573-10 2012 In binary logistic regression analysis, a model containing previous bisphosphonate treatment, age, body mass index, lymphocytes and visfatin, which predicted zoledronate-induced APR with 82 1% sensitivity and 73 9% specificity, was selected. Diphosphonates 68-82 phorbol-12-myristate-13-acetate-induced protein 1 Homo sapiens 178-181 23032740-0 2012 In vivo phosphoantigen levels in bisphosphonate-treated human breast tumors trigger Vgamma9Vdelta2 T-cell antitumor cytotoxicity through ICAM-1 engagement. Diphosphonates 33-47 intercellular adhesion molecule 1 Homo sapiens 137-143 23193622-6 2004 In an effort to develop an imaging compound that does not have the limitations of tracers that are currently used to detect SREs with scintigraphy or PET, a bisphosphonate labeled with (68)Ga was developed and shown to be potentially useful for imaging the mouse skeletal system with PET (5). Diphosphonates 157-171 thyroid stimulating hormone receptor Mus musculus 150-153 23193622-6 2004 In an effort to develop an imaging compound that does not have the limitations of tracers that are currently used to detect SREs with scintigraphy or PET, a bisphosphonate labeled with (68)Ga was developed and shown to be potentially useful for imaging the mouse skeletal system with PET (5). Diphosphonates 157-171 thyroid stimulating hormone receptor Mus musculus 284-287 22992781-0 2012 Bisphosphonates are safe after ORIF for distal radial fractures: commentary on an article by Hyun Sik Gong, MD, PhD, et al. Diphosphonates 0-15 salt inducible kinase 1 Homo sapiens 98-101 22627198-6 2012 Treatment changes were necessary only in cases of IatroMed and EndoG, requiring a lowered prescription of PTH-lowering therapies and the addition of bisphosphonates for EndoG. Diphosphonates 149-164 endonuclease G Homo sapiens 63-68 23079134-8 2012 Serum TRACP-5b was significantly increased during the follow-up period in the Bis + statin group, but only at 18 months in the Bis group. Diphosphonates 78-81 acid phosphatase 5, tartrate resistant Homo sapiens 6-14 22750450-0 2012 Bisphosphonates improve trabecular bone mass and normalize cortical thickness in ovariectomized, osteoblast connexin43 deficient mice. Diphosphonates 0-15 gap junction protein, alpha 1 Mus musculus 108-118 22750450-2 2012 Cx43 has also been proposed to mediate an anti-apoptotic effect of bisphosphonates, potent inhibitors of bone resorption. Diphosphonates 67-82 gap junction protein, alpha 1 Mus musculus 0-4 22750450-3 2012 We studied whether bisphosphonates are effective in protecting mice with a conditional Cx43 gene deletion in osteoblasts and osteocytes (cKO) from the consequences of ovariectomy on bone mass and strength. Diphosphonates 19-34 gap junction protein, alpha 1 Mus musculus 87-91 22807219-3 2012 Additionally a bisphosphonate function is introduced in the PEG molecule to allow targeting of hydroxyapatite rich tissues, like bone. Diphosphonates 15-29 progestagen associated endometrial protein Homo sapiens 60-63 22986334-0 2012 Serum VEGF levels as predictive marker of bisphosphonate-related osteonecrosis of the jaw. Diphosphonates 42-56 vascular endothelial growth factor A Homo sapiens 6-10 22882004-0 2012 Development of novel bisphosphonate prodrugs of doxorubicin for targeting bone metastases that are cleaved pH dependently or by cathepsin B: synthesis, cleavage properties, and binding properties to hydroxyapatite as well as bone matrix. Diphosphonates 21-35 cathepsin B Homo sapiens 128-139 22886306-6 2012 CaSR inhibition increased blood calcium concentration in animals pretreated with a bisphosphonate, indicating that the increase did not result from release of bone calcium. Diphosphonates 83-97 calcium-sensing receptor Rattus norvegicus 0-4 22339777-2 2012 We aimed to investigate the effect of CYP2C8 rs1934951 SNP and its relationship to a number of clinical and biochemical factors in 46 Hungarian subjects with bisphosphonate-induced ONJ. Diphosphonates 158-172 cytochrome P450 family 2 subfamily C member 8 Homo sapiens 38-44 22579611-0 2012 Bisphosphonate- and statin-induced enhancement of OPG expression and inhibition of CD9, M-CSF, and RANKL expressions via inhibition of the Ras/MEK/ERK pathway and activation of p38MAPK in mouse bone marrow stromal cell line ST2. Diphosphonates 0-14 tumor necrosis factor receptor superfamily, member 11b (osteoprotegerin) Mus musculus 50-53 22579611-0 2012 Bisphosphonate- and statin-induced enhancement of OPG expression and inhibition of CD9, M-CSF, and RANKL expressions via inhibition of the Ras/MEK/ERK pathway and activation of p38MAPK in mouse bone marrow stromal cell line ST2. Diphosphonates 0-14 CD9 antigen Mus musculus 83-86 22579611-0 2012 Bisphosphonate- and statin-induced enhancement of OPG expression and inhibition of CD9, M-CSF, and RANKL expressions via inhibition of the Ras/MEK/ERK pathway and activation of p38MAPK in mouse bone marrow stromal cell line ST2. Diphosphonates 0-14 colony stimulating factor 1 (macrophage) Mus musculus 88-93 22579611-0 2012 Bisphosphonate- and statin-induced enhancement of OPG expression and inhibition of CD9, M-CSF, and RANKL expressions via inhibition of the Ras/MEK/ERK pathway and activation of p38MAPK in mouse bone marrow stromal cell line ST2. Diphosphonates 0-14 tumor necrosis factor (ligand) superfamily, member 11 Mus musculus 99-104 22579611-0 2012 Bisphosphonate- and statin-induced enhancement of OPG expression and inhibition of CD9, M-CSF, and RANKL expressions via inhibition of the Ras/MEK/ERK pathway and activation of p38MAPK in mouse bone marrow stromal cell line ST2. Diphosphonates 0-14 midkine Mus musculus 143-146 22579611-0 2012 Bisphosphonate- and statin-induced enhancement of OPG expression and inhibition of CD9, M-CSF, and RANKL expressions via inhibition of the Ras/MEK/ERK pathway and activation of p38MAPK in mouse bone marrow stromal cell line ST2. Diphosphonates 0-14 mitogen-activated protein kinase 1 Mus musculus 147-150 22579611-0 2012 Bisphosphonate- and statin-induced enhancement of OPG expression and inhibition of CD9, M-CSF, and RANKL expressions via inhibition of the Ras/MEK/ERK pathway and activation of p38MAPK in mouse bone marrow stromal cell line ST2. Diphosphonates 0-14 mitogen-activated protein kinase 14 Mus musculus 177-184 22579611-0 2012 Bisphosphonate- and statin-induced enhancement of OPG expression and inhibition of CD9, M-CSF, and RANKL expressions via inhibition of the Ras/MEK/ERK pathway and activation of p38MAPK in mouse bone marrow stromal cell line ST2. Diphosphonates 0-14 interleukin 1 receptor-like 1 Mus musculus 224-227 22579611-3 2012 In this study, we investigated whether bisphosphonates and statins increase OPG expression and inhibit the expression of CD9, M-CSF, and RANKL in the bone marrow-derived stromal cell line ST2. Diphosphonates 39-54 tumor necrosis factor receptor superfamily, member 11b (osteoprotegerin) Mus musculus 76-79 22579611-3 2012 In this study, we investigated whether bisphosphonates and statins increase OPG expression and inhibit the expression of CD9, M-CSF, and RANKL in the bone marrow-derived stromal cell line ST2. Diphosphonates 39-54 CD9 antigen Mus musculus 121-124 22579611-3 2012 In this study, we investigated whether bisphosphonates and statins increase OPG expression and inhibit the expression of CD9, M-CSF, and RANKL in the bone marrow-derived stromal cell line ST2. Diphosphonates 39-54 colony stimulating factor 1 (macrophage) Mus musculus 126-131 22579611-3 2012 In this study, we investigated whether bisphosphonates and statins increase OPG expression and inhibit the expression of CD9, M-CSF, and RANKL in the bone marrow-derived stromal cell line ST2. Diphosphonates 39-54 tumor necrosis factor (ligand) superfamily, member 11 Mus musculus 137-142 22579611-3 2012 In this study, we investigated whether bisphosphonates and statins increase OPG expression and inhibit the expression of CD9, M-CSF, and RANKL in the bone marrow-derived stromal cell line ST2. Diphosphonates 39-54 interleukin 1 receptor-like 1 Mus musculus 188-191 22579611-5 2012 Futhermore, bisphosphonates and statins decreased the membrane localization of Ras and phosphorylated ERK1/2, and activated the p38MAPK. Diphosphonates 12-27 mitogen-activated protein kinase 3 Mus musculus 102-108 22579611-5 2012 Futhermore, bisphosphonates and statins decreased the membrane localization of Ras and phosphorylated ERK1/2, and activated the p38MAPK. Diphosphonates 12-27 mitogen-activated protein kinase 14 Mus musculus 128-135 22579611-6 2012 This indicates that bisphosphonates and statins enhanced OPG expression, and inhibited the expression of CD9, M-CSF, and RANKL through blocking the Ras/ERK pathway and activating p38MAPK. Diphosphonates 20-35 tumor necrosis factor receptor superfamily, member 11b (osteoprotegerin) Mus musculus 57-60 22579611-6 2012 This indicates that bisphosphonates and statins enhanced OPG expression, and inhibited the expression of CD9, M-CSF, and RANKL through blocking the Ras/ERK pathway and activating p38MAPK. Diphosphonates 20-35 CD9 antigen Mus musculus 105-108 22579611-6 2012 This indicates that bisphosphonates and statins enhanced OPG expression, and inhibited the expression of CD9, M-CSF, and RANKL through blocking the Ras/ERK pathway and activating p38MAPK. Diphosphonates 20-35 colony stimulating factor 1 (macrophage) Mus musculus 110-115 22579611-6 2012 This indicates that bisphosphonates and statins enhanced OPG expression, and inhibited the expression of CD9, M-CSF, and RANKL through blocking the Ras/ERK pathway and activating p38MAPK. Diphosphonates 20-35 tumor necrosis factor (ligand) superfamily, member 11 Mus musculus 121-126 22579611-6 2012 This indicates that bisphosphonates and statins enhanced OPG expression, and inhibited the expression of CD9, M-CSF, and RANKL through blocking the Ras/ERK pathway and activating p38MAPK. Diphosphonates 20-35 mitogen-activated protein kinase 1 Mus musculus 152-155 22579611-6 2012 This indicates that bisphosphonates and statins enhanced OPG expression, and inhibited the expression of CD9, M-CSF, and RANKL through blocking the Ras/ERK pathway and activating p38MAPK. Diphosphonates 20-35 mitogen-activated protein kinase 14 Mus musculus 179-186 22884353-0 2012 Design of potent bisphosphonate inhibitors of the human farnesyl pyrophosphate synthase via targeted interactions with the active site "capping" phenyls. Diphosphonates 17-31 farnesyl diphosphate synthase Homo sapiens 56-87 22884353-1 2012 Nitrogen-containing bisphosphonates (N-BPs) are potent active site inhibitors of the human farnesyl pyrophosphate synthase (hFPPS) and valuable human therapeutics for the treatment of bone-related malignancies. Diphosphonates 20-35 farnesyl diphosphate synthase Homo sapiens 91-122 22884353-1 2012 Nitrogen-containing bisphosphonates (N-BPs) are potent active site inhibitors of the human farnesyl pyrophosphate synthase (hFPPS) and valuable human therapeutics for the treatment of bone-related malignancies. Diphosphonates 20-35 farnesyl diphosphate synthase Homo sapiens 124-129 22947548-0 2012 Bisphosphonate therapy for painless fracture: change of HSAN 1 clinical course with biphosphonate and Vitamin D therapy. Diphosphonates 0-14 serine palmitoyltransferase long chain base subunit 1 Homo sapiens 56-62 22947548-0 2012 Bisphosphonate therapy for painless fracture: change of HSAN 1 clinical course with biphosphonate and Vitamin D therapy. Diphosphonates 84-97 serine palmitoyltransferase long chain base subunit 1 Homo sapiens 56-62 22947548-3 2012 The authors believe that combined bisphosphonate and vitamin D therapy is the treatment of choice for progressive bony changes in HSAN1. Diphosphonates 34-48 serine palmitoyltransferase long chain base subunit 1 Homo sapiens 130-135 22723339-1 2012 Statins and bisphosphonates are two distinct classes of isoprenoid pathway inhibitors targeting downstream enzyme to HMG-CoA reductase (upstream enzyme) and farnesyl-pyrophosphate synthase, respectively. Diphosphonates 12-27 3-hydroxy-3-methylglutaryl-Coenzyme A reductase Mus musculus 117-134 22723339-1 2012 Statins and bisphosphonates are two distinct classes of isoprenoid pathway inhibitors targeting downstream enzyme to HMG-CoA reductase (upstream enzyme) and farnesyl-pyrophosphate synthase, respectively. Diphosphonates 12-27 farnesyl diphosphate synthetase Mus musculus 157-188 21938481-0 2012 Bisphosphonates modulate the expression of OPG and M-CSF in hMSC-derived osteoblasts. Diphosphonates 0-15 basic transcription factor 3 pseudogene 11 Homo sapiens 43-46 21938481-0 2012 Bisphosphonates modulate the expression of OPG and M-CSF in hMSC-derived osteoblasts. Diphosphonates 0-15 colony stimulating factor 1 Homo sapiens 51-56 21787288-7 2012 The use of selective EP4 agonists reversed established osteoporotic changes, enhanced the boneimplant interface strength and was shown to have a synergistic effect when used with other bone cell targeting pharmacological agents such as BMP-2 and bisphosphonates. Diphosphonates 246-261 prostaglandin E receptor 4 Homo sapiens 21-24 22223192-0 2012 A role for C-terminal cross-linking telopeptide (CTX) level to predict the development of bisphosphonate-related osteonecrosis of the jaws (BRONJ) following oral surgery? Diphosphonates 90-104 cytochrome P450 family 27 subfamily A member 1 Homo sapiens 49-52 22447156-12 2012 In conclusion, bisphosphonates directly inhibited RANKL-stimulated osteoclast differentiation and fusion in RAW cells. Diphosphonates 15-30 tumor necrosis factor (ligand) superfamily, member 11 Mus musculus 50-55 21151198-0 2012 Common allelic variants of the farnesyl diphosphate synthase gene influence the response of osteoporotic women to bisphosphonates. Diphosphonates 114-129 farnesyl diphosphate synthase Homo sapiens 31-60 24367197-0 2012 Aromatase inhibitor-associated bone loss and its management with bisphosphonates in patients with breast cancer. Diphosphonates 65-80 cytochrome P450 family 19 subfamily A member 1 Homo sapiens 0-9 22969979-1 2012 The aim of this study was to explore the effects of the bisphosphonate zoledronate on calcification induced by inorganic phosphate (Pi) and/or bone morphogenetic protein 2 (BMP-2) and the underlying mechanisms. Diphosphonates 56-70 bone morphogenetic protein 2 Rattus norvegicus 143-171 22143730-0 2012 Study of serum CTX in 50 oral surgical patients treated with oral bisphosphonates. Diphosphonates 66-81 cytochrome P450 family 27 subfamily A member 1 Homo sapiens 15-18 22448795-3 2012 AIM: We aimed to examine the association between the aromatase polymorphism g.132810C>T, and the estrogen receptor polymorphisms g.156705T>C and g.156751A>G, and the risk of BP-related ONJ. Diphosphonates 183-185 estrogen receptor 1 Homo sapiens 100-117 22348981-6 2012 One implant in each pair was coated with a thin fibrinogen layer containing 2 bisphosphonates. Diphosphonates 78-93 fibrinogen beta chain Homo sapiens 48-58 22348981-14 2012 In conclusion, a thin, bisphosphonate-eluting fibrinogen coating might improve the fixation of metal implants in human bone. Diphosphonates 23-37 fibrinogen beta chain Homo sapiens 46-56 22278430-4 2012 OBJECTIVE: The aim of the study was to describe the long-term follow-up of a JMC patient with regard to the management of hypercalciuria, the evaluation of FGF23 levels under bisphosphonate treatment, and the investigation of cardiovascular repercussion of chronic hypercalcemia. Diphosphonates 175-189 fibroblast growth factor 23 Homo sapiens 156-161 22969979-1 2012 The aim of this study was to explore the effects of the bisphosphonate zoledronate on calcification induced by inorganic phosphate (Pi) and/or bone morphogenetic protein 2 (BMP-2) and the underlying mechanisms. Diphosphonates 56-70 bone morphogenetic protein 2 Rattus norvegicus 173-178 22178539-0 2012 Bisphosphonate treatment of postmenopausal osteoporosis is associated with a dose dependent increase in serum sclerostin. Diphosphonates 0-14 sclerostin Homo sapiens 110-120 22419140-7 2012 Cheney Syndrom (HCS) was diagnosed clinically and radiologically and a treatment with bisphosphonates was introduced. Diphosphonates 86-101 holocarboxylase synthetase Homo sapiens 16-19 22178539-10 2012 In conclusions, decreased bone formation after several months of bisphosphonate therapy is associated with increased serum levels of sclerostin. Diphosphonates 65-79 sclerostin Homo sapiens 133-143 21643886-10 2012 Screening for PDB is warranted in at-risk individuals because of the benefit of early treatment with the new powerful bisphosphonates that hold the potential for prevention of disease. Diphosphonates 118-133 PDB1 Homo sapiens 14-17 22226973-6 2012 Our aim was also to characterize the effects of bisphosphonates on NF1 osteoclasts in vitro. Diphosphonates 48-63 neurofibromin 1 Homo sapiens 67-70 21864230-11 2012 The more potent nitrogen-containing BPs inhibit FPPS, a key enzyme in the mevalonate pathway. Diphosphonates 36-39 farnesyl diphosphate synthase Homo sapiens 48-52 22230328-2 2012 Previously, we hypothesized that intracellular survival signaling is initiated by interaction of BPs with Cx43. Diphosphonates 97-100 gap junction protein, alpha 1 Rattus norvegicus 106-110 22230328-4 2012 In addition, both BPs and the PTP inhibitor Na(3)VO(4) increased proliferation of cells expressing Cx43 or not. Diphosphonates 18-21 gap junction protein, alpha 1 Rattus norvegicus 99-103 20938793-0 2012 Influence of bisphosphonates on the osteoblast RANKL and OPG gene expression in vitro. Diphosphonates 13-28 TNF superfamily member 11 Homo sapiens 47-52 20938793-8 2012 The non-nitrogen-containing bisphosphonate clodronate, however, effected OPG and RANKL gene expression much less, even at higher concentrations of 5 x 10(-3) M. The above-mentioned data suggest an enhanced RANKL/OPG gene expression after stimulation by bisphosphonates. Diphosphonates 253-268 TNF superfamily member 11 Homo sapiens 206-211 20938793-0 2012 Influence of bisphosphonates on the osteoblast RANKL and OPG gene expression in vitro. Diphosphonates 13-28 TNF receptor superfamily member 11b Homo sapiens 57-60 20938793-3 2012 The objective of this study was to evaluate the effect of bisphosphonates on the gene expression of receptor activator of NF-kappaB ligand (RANKL) and osteoprotegerin (OPG) in vitro. Diphosphonates 58-73 TNF superfamily member 11 Homo sapiens 100-138 20938793-3 2012 The objective of this study was to evaluate the effect of bisphosphonates on the gene expression of receptor activator of NF-kappaB ligand (RANKL) and osteoprotegerin (OPG) in vitro. Diphosphonates 58-73 TNF superfamily member 11 Homo sapiens 140-145 20938793-3 2012 The objective of this study was to evaluate the effect of bisphosphonates on the gene expression of receptor activator of NF-kappaB ligand (RANKL) and osteoprotegerin (OPG) in vitro. Diphosphonates 58-73 TNF receptor superfamily member 11b Homo sapiens 151-166 20938793-3 2012 The objective of this study was to evaluate the effect of bisphosphonates on the gene expression of receptor activator of NF-kappaB ligand (RANKL) and osteoprotegerin (OPG) in vitro. Diphosphonates 58-73 TNF receptor superfamily member 11b Homo sapiens 168-171 20938793-7 2012 The results showed a moderate enhancement of OPG gene expression whereas RANKL gene expression was strongly increased by nitrogen-containing bisphosphonates reaching a maximum after 14 days at high concentrations of 5 x 10(-5) M. Lower concentrations did not enhance the RANKL and OPG expression considerably. Diphosphonates 141-156 TNF superfamily member 11 Homo sapiens 73-78 20938793-8 2012 The non-nitrogen-containing bisphosphonate clodronate, however, effected OPG and RANKL gene expression much less, even at higher concentrations of 5 x 10(-3) M. The above-mentioned data suggest an enhanced RANKL/OPG gene expression after stimulation by bisphosphonates. Diphosphonates 28-42 TNF receptor superfamily member 11b Homo sapiens 73-76 20938793-8 2012 The non-nitrogen-containing bisphosphonate clodronate, however, effected OPG and RANKL gene expression much less, even at higher concentrations of 5 x 10(-3) M. The above-mentioned data suggest an enhanced RANKL/OPG gene expression after stimulation by bisphosphonates. Diphosphonates 28-42 TNF superfamily member 11 Homo sapiens 81-86 20938793-8 2012 The non-nitrogen-containing bisphosphonate clodronate, however, effected OPG and RANKL gene expression much less, even at higher concentrations of 5 x 10(-3) M. The above-mentioned data suggest an enhanced RANKL/OPG gene expression after stimulation by bisphosphonates. Diphosphonates 28-42 TNF superfamily member 11 Homo sapiens 206-211 20938793-8 2012 The non-nitrogen-containing bisphosphonate clodronate, however, effected OPG and RANKL gene expression much less, even at higher concentrations of 5 x 10(-3) M. The above-mentioned data suggest an enhanced RANKL/OPG gene expression after stimulation by bisphosphonates. Diphosphonates 28-42 TNF receptor superfamily member 11b Homo sapiens 212-215 21953593-2 2012 To inhibit bone metastasis, catalase was conjugated with 3,5-di(ethylamino-2,2-bisphosphono)benzoic acid (Bip), a derivative of bone-seeking bisphosphonates, polyethylene glycol (PEG), or both. Diphosphonates 141-156 catalase Mus musculus 28-36 22306909-2 2012 Using in vivo targeting of bisphosphonate-reactive gammadelta T cells by adding low-dose interleukin-2 to zoledronic acid, we evaluated the safety, pharmacodynamics, and antitumor activity of this immunotherapy approach in 21 adults with advanced malignancies (renal cell carcinoma [RCC], malignant melanoma, and acute myeloid leukemia). Diphosphonates 27-41 interleukin 2 Homo sapiens 89-102 22257870-0 2012 Painful trigeminal neuropathy induced by oral bisphosphonate-related osteonecrosis of the jaw: a new etiology for the numb-chin syndrome. Diphosphonates 46-60 NUMB endocytic adaptor protein Homo sapiens 118-122 21819236-6 2012 Genome-wide studies have not yet found clear associations for drug-induced cardiotoxicity, but for bisphosphonate-induced necrosis of the jaw, polymorphisms in the cytochrome P450 CYP2C8 may predict susceptibility. Diphosphonates 99-113 cytochrome P450 family 2 subfamily C member 8 Homo sapiens 180-186 22273876-4 2012 Our patient was treated with a bisphosphonate and the prolactin antagonist, cabergoline, resulting in the inhibition of fibrous dysplasia and involution of both the prolactinoma and growth hormone excess. Diphosphonates 31-45 growth hormone 1 Homo sapiens 182-196 20641269-18 2004 Nitrogen-containing synthetic diphosphonates are inhibitors of farnesyl diphosphate synthase (FDPS) of osteoclast and are used for treatment of osteoporosis (bone resorption) (9). Diphosphonates 30-44 farnesyl diphosphate synthase Rattus norvegicus 63-92 20641269-18 2004 Nitrogen-containing synthetic diphosphonates are inhibitors of farnesyl diphosphate synthase (FDPS) of osteoclast and are used for treatment of osteoporosis (bone resorption) (9). Diphosphonates 30-44 farnesyl diphosphate synthase Rattus norvegicus 94-98 22783453-1 2012 AIM: This study investigates the association between cross linked C-terminal telopetide test (CTX) and individual surgical risk of osteonecrosis in patients taking oral bisphosphonates. Diphosphonates 169-184 cytochrome P450 family 27 subfamily A member 1 Homo sapiens 94-97 22308113-0 2012 Successful Treatment of MMP-9-Expressing Angiosarcoma with Low-Dose Docetaxel and Bisphosphonate. Diphosphonates 82-96 matrix metallopeptidase 9 Homo sapiens 24-29 22783453-5 2012 As for CTX, patients treated with oral bisphosphonates showed a mean value of serum Ctelopetides of 0.2869 ng/ml. Diphosphonates 39-54 cytochrome P450 family 27 subfamily A member 1 Homo sapiens 7-10 23251041-3 2012 Recent studies have confirmed FPS as a molecular target of bisphosphonates for drug development against bone diseases as well as pathogens. Diphosphonates 59-74 farnesyl diphosphate synthase Gallus gallus 30-33 23227342-13 2012 With disease progression, MMP-2 expression increases in both mM and surrounding stromal cells, with implications for the use of bisphosphonates or MMP-2 inhibitors. Diphosphonates 128-143 matrix metallopeptidase 2 Homo sapiens 26-31 22830074-0 2012 Modulating P2X7 Receptor Signaling during Rheumatoid Arthritis: New Therapeutic Approaches for Bisphosphonates. Diphosphonates 95-110 purinergic receptor P2X 7 Homo sapiens 11-24 22456437-0 2012 Osteoporosis-pseudoglioma syndrome: three novel mutations in the LRP5 gene and response to bisphosphonate treatment. Diphosphonates 91-105 LDL receptor related protein 5 Homo sapiens 65-69 22456437-3 2012 We present three novel homozygous LRP5 mutations found in 3 unrelated Turkish children with consanguineous parents, along with clinical phenotypes and response to treatment with bisphosphonates (bisP). Diphosphonates 178-193 LDL receptor related protein 5 Homo sapiens 34-38 21956654-1 2012 The use of intravenous nitrogen-containing bisphosphonates (N-BPs) is associated with the appearance of an acute phase response (APR) in a proportion of the patients for reasons that are poorly understood. Diphosphonates 43-58 phorbol-12-myristate-13-acetate-induced protein 1 Homo sapiens 129-132 22783333-6 2012 Together with well known anti-resorptive agents (like bisphosphonates, oestrogen and selective oestrogen receptor modulators) in the past few years anabolic therapy with parathyroid hormone (PTH) has become available for the treatment of severe osteoporosis. Diphosphonates 54-69 parathyroid hormone Homo sapiens 170-189 22372177-7 2012 Recently genetic testing has become available for TGF-beta1 mutation Several therapeutic agents including biphosphonates, NSAIDs, prednisone and losartan have been described as therapeutic options with mixed results, as described in our cases. Diphosphonates 106-120 transforming growth factor beta 1 Homo sapiens 50-59 22830074-10 2012 Bisphosphonates are arising per se as promising anti-inflammatory drugs to treat RA, and this therapy could be improved when administrated in combination with P2X7 receptor antagonists. Diphosphonates 0-15 purinergic receptor P2X 7 Homo sapiens 159-172 20865462-6 2011 Nephrotic syndrome due to collapsing FSGS is a serious complication of treatment with bisphosphonates, especially of i.v. Diphosphonates 86-101 actinin alpha 4 Homo sapiens 37-41 21441060-6 2011 Although no randomized placebo-controlled trials are available, there is general agreement that nonsteroidal antiinflammatory drugs constitute the best first-line treatment and that bisphosphonates and biotherapies such as TNFalpha antagonists are effective in the most severe forms. Diphosphonates 182-197 tumor necrosis factor Homo sapiens 223-231 22161446-17 2011 Bisphosphonates compared with placebo or no intervention seem to decrease the urinary amino telopeptides of collagen I (NTx) concentration (MD -16.93 nmol bone collagen equivalents/mmol creatinine; 95% CI -23.77 to -10.10; 2 trials with 88 patients; I2 = 0%) and serum osteocalcin (SMD -0.81; 95% CI -1.22 to -0.39; 3 trials with 100 patients; I2 = 34 %) concentration. Diphosphonates 0-15 bone gamma-carboxyglutamate protein Homo sapiens 269-280 21983021-14 2011 Treatment of osteoclast cultures with alendronate, a bisphosphonate, suppressed the formation of TRAP-marks and resorption pits without affecting the cell viability. Diphosphonates 53-67 acid phosphatase 5, tartrate resistant Mus musculus 97-101 21932012-5 2011 We report on the long-term survival of a severe case of GACI linked to a novel homozygous missense mutation c.583T/C in the ENPP1 gene, diagnosed prenatally, and treated with bisphosphonates. Diphosphonates 175-190 ectonucleotide pyrophosphatase/phosphodiesterase 1 Homo sapiens 124-129 22091898-6 2011 Second-generation bisphosphonates are nitrogen-containing agents; these inhibit osteoclast vesicular trafficking, membrane ruffling, morphology, and cytoskeletal arrangement by inhibiting farnesyl diphosphate synthase in the mevalonate pathway. Diphosphonates 18-33 farnesyl diphosphate synthase Homo sapiens 188-217 21550960-7 2011 Bisphosphonate therapy in the vitamin D-sufficient group led to a 32.7% decrease in BSAP (P = .01). Diphosphonates 0-14 paired box 5 Homo sapiens 84-88 21751240-4 2011 Thus, understanding the ability of bisphosphonates to modulate SOCS3 is necessary to qualify their contribution to these disorders. Diphosphonates 35-50 suppressor of cytokine signaling 3 Homo sapiens 63-68 21921248-5 2011 Therefore, in periodontal tissues pre-exposed to bisphosphonate, bacterial infection at tooth extraction sites caused diminished KGF expression in GFs, leading to a delay in the epithelial wound-healing process that was mitigated by antibiotics. Diphosphonates 49-63 fibroblast growth factor 7 Mus musculus 129-132 21903868-0 2011 A novel bisphosphonate inhibitor of squalene synthase combined with a statin or a nitrogenous bisphosphonate in vitro. Diphosphonates 8-22 farnesyl-diphosphate farnesyltransferase 1 Homo sapiens 36-53 21903868-3 2011 Herein, we have identified novel bisphosphonates as potent and specific inhibitors of SQS, including the tetrasodium salt of 9-biphenyl-4,8-dimethyl-nona-3,7-dienyl-1,1-bisphosphonic acid (compound 5). Diphosphonates 33-48 farnesyl-diphosphate farnesyltransferase 1 Homo sapiens 86-89 21685474-2 2011 Previous studies showed that the presence of one or two minor alleles of the cytochrome P450, subfamily 2C polypeptide 8 gene (CYP2C8) polymorphism rs1934951 was an independent prognostic marker associated with development of osteonecrosis of the jaw in multiple myeloma patients treated with bisphosphonates. Diphosphonates 293-308 cytochrome P450 family 4 subfamily F member 3 Homo sapiens 77-120 22073949-1 2011 OBJECTIVES: The aim of the study is to evaluate the changes of bone mineral density (BMD), incidence of pathological fractures and to asses the effect of bisphosphonate therapy in prostate cancer patients (PCa) on androgen deprivation therapy (ADT) with the use of LHRH. Diphosphonates 154-168 gonadotropin releasing hormone 1 Homo sapiens 265-269 21811962-11 2011 However, the effect of PTH on osteoclasts is, at least partly, restricted in patients taking BPs. Diphosphonates 93-96 parathyroid hormone Homo sapiens 23-26 21685474-2 2011 Previous studies showed that the presence of one or two minor alleles of the cytochrome P450, subfamily 2C polypeptide 8 gene (CYP2C8) polymorphism rs1934951 was an independent prognostic marker associated with development of osteonecrosis of the jaw in multiple myeloma patients treated with bisphosphonates. Diphosphonates 293-308 cytochrome P450 family 2 subfamily C member 8 Homo sapiens 127-133 21111853-8 2011 These discoveries are also giving insights into some of the adverse effects of bisphosphonates, such as the acute phase reaction that is triggered by inhibition of FPP synthase in peripheral blood monocytes. Diphosphonates 79-94 farnesyl diphosphate synthase Homo sapiens 164-176 21598905-5 2011 The efficiency of L-selectin inhibition increases in the order carboxylate < phosphate < phosphonate sulfonate < bisphosphonate < sulfate. Diphosphonates 124-138 selectin L Homo sapiens 18-28 21714093-2 2011 Here, we report the synthesis and biological evaluation of a new class of MMP inhibitors characterized by a bisphosphonate function as the zinc binding group. Diphosphonates 108-122 matrix metallopeptidase 2 Homo sapiens 74-77 21714093-4 2011 Docking experiments were performed to clarify the mode of binding of bisphosphonate inhibitors in the active site of MMP-2. Diphosphonates 69-83 matrix metallopeptidase 2 Homo sapiens 117-122 21714093-5 2011 The most promising of the studied bisphosphonates showed nanomolar inhibition against MMP-2 and resulted in potent inhibition of osteoclastic bone resorption in vitro. Diphosphonates 34-49 matrix metallopeptidase 2 Homo sapiens 86-91 21111853-4 2011 The considerably more potent nitrogen-containing bisphosphonates are not metabolised but potently inhibit farnesyl pyrophosphate (FPP) synthase, a key enzyme of the mevalonate pathway. Diphosphonates 49-64 farnesyl diphosphate synthase Homo sapiens 106-143 21843332-0 2011 Increased human defensine levels hint at an inflammatory etiology of bisphosphonate-associated osteonecrosis of the jaw: an immunohistological study. Diphosphonates 69-83 histidine triad nucleotide binding protein 1 Homo sapiens 33-37 21843332-3 2011 In order to gain insight into the possible impairment of hBD metabolism in bisphosphonate-associated osteonecrosis of the jaws (BONJ), the present exploratory study was designed so as to determine the qualitative and quantitative expression of afore mentioned hBDs in BONJ and infected osteoradionecrosis (ORN), both of which represent inflammatory bone diseases. Diphosphonates 75-89 HBD Homo sapiens 57-60 21768643-3 2011 As an additional pharmaceutical intervention, we describe the combined use of rhBMP-2 and the bisphosphonate zoledronic acid in a mouse model of NF1-deficient fracture repair. Diphosphonates 94-108 neurofibromin 1 Mus musculus 145-148 21726429-0 2011 Bisphosphonate-associated osteonecrosis of the jaw is linked to suppressed TGFbeta1-signaling and increased Galectin-3 expression: a histological study on biopsies. Diphosphonates 0-14 transforming growth factor beta 1 Homo sapiens 75-83 21726429-0 2011 Bisphosphonate-associated osteonecrosis of the jaw is linked to suppressed TGFbeta1-signaling and increased Galectin-3 expression: a histological study on biopsies. Diphosphonates 0-14 galectin 3 Homo sapiens 108-118 20727997-6 2011 Remarkably, this Cx43-dependent survival effect of bisphosphonates is independent of gap junctions and results from opening of Cx43 hemichannels. Diphosphonates 51-66 gap junction protein, alpha 3 Mus musculus 17-21 20727997-6 2011 Remarkably, this Cx43-dependent survival effect of bisphosphonates is independent of gap junctions and results from opening of Cx43 hemichannels. Diphosphonates 51-66 gap junction protein, alpha 3 Mus musculus 127-131 21419243-0 2011 The gunmetal mouse reveals Rab geranylgeranyl transferase to be the major molecular target of phosphonocarboxylate analogues of bisphosphonates. Diphosphonates 128-143 Rab geranylgeranyl transferase, a subunit Mus musculus 4-12 21497677-7 2011 A major advance was the discovery that the anti-resorptive effects of the nitrogen-containing bisphosphonates (including alendronate, risedronate, ibandronate, and zoledronate) on osteoclasts appear to result from their potency as inhibitors of the enzyme farnesyl pyrophosphate synthase (FPPS), a key branch-point enzyme in the mevalonate pathway. Diphosphonates 94-109 farnesyl diphosphate synthase Homo sapiens 256-287 21497677-7 2011 A major advance was the discovery that the anti-resorptive effects of the nitrogen-containing bisphosphonates (including alendronate, risedronate, ibandronate, and zoledronate) on osteoclasts appear to result from their potency as inhibitors of the enzyme farnesyl pyrophosphate synthase (FPPS), a key branch-point enzyme in the mevalonate pathway. Diphosphonates 94-109 farnesyl diphosphate synthase Homo sapiens 289-293 21551338-0 2011 Bisphosphonates inhibit expression of p63 by oral keratinocytes. Diphosphonates 0-15 tumor protein p63 Homo sapiens 38-41 21555003-14 2011 The major enzyme target for bisphosphonates is farnesyl pyrophosphate synthase (FPPS), and the crystal structure elucidated for this enzyme reveals how BPs bind to and inhibit at the active site via their critical N atoms. Diphosphonates 28-43 farnesyl diphosphate synthase Homo sapiens 47-78 21555003-14 2011 The major enzyme target for bisphosphonates is farnesyl pyrophosphate synthase (FPPS), and the crystal structure elucidated for this enzyme reveals how BPs bind to and inhibit at the active site via their critical N atoms. Diphosphonates 28-43 farnesyl diphosphate synthase Homo sapiens 80-84 21555003-14 2011 The major enzyme target for bisphosphonates is farnesyl pyrophosphate synthase (FPPS), and the crystal structure elucidated for this enzyme reveals how BPs bind to and inhibit at the active site via their critical N atoms. Diphosphonates 152-155 farnesyl diphosphate synthase Homo sapiens 47-78 21555003-14 2011 The major enzyme target for bisphosphonates is farnesyl pyrophosphate synthase (FPPS), and the crystal structure elucidated for this enzyme reveals how BPs bind to and inhibit at the active site via their critical N atoms. Diphosphonates 152-155 farnesyl diphosphate synthase Homo sapiens 80-84 21551338-4 2011 Oral and intravenous bisphosphonate-treated ONJ sites had reduced numbers of basal epithelial progenitor cells, as demonstrated by a 13.8+-1.1% and 31.9+-5.8% reduction of p63 expression, respectively. Diphosphonates 21-35 tumor protein p63 Homo sapiens 172-175 21551338-8 2011 Analysis of our data suggests that bisphosphonate treatment may delay oral epithelial healing by interfering with p63-positive progenitor cells in the basal layer of the oral epithelium in a mevalonate-pathway-dependent manner. Diphosphonates 35-49 tumor protein p63 Homo sapiens 114-117 21321287-1 2011 BACKGROUND: Proton pump inhibitors (PPIs) are widely used in elderly patients and are frequently coadministered in users of oral bisphosphonates. Diphosphonates 129-144 ATPase H+/K+ transporting subunit alpha Homo sapiens 12-23 21251073-0 2011 Vascular endothelial growth factor genetic polymorphisms and haplotypes in female patients with bisphosphonate-related osteonecrosis of the jaws. Diphosphonates 96-110 vascular endothelial growth factor A Homo sapiens 0-34 21251073-1 2011 OBJECTIVE: To investigate the polymorphisms of the vascular endothelial growth factor (VEGF) gene in relation to female patients who developed bisphosphonate-related osteonecrosis of the jaws (BRONJ). Diphosphonates 143-157 vascular endothelial growth factor A Homo sapiens 51-85 21251073-1 2011 OBJECTIVE: To investigate the polymorphisms of the vascular endothelial growth factor (VEGF) gene in relation to female patients who developed bisphosphonate-related osteonecrosis of the jaws (BRONJ). Diphosphonates 143-157 vascular endothelial growth factor A Homo sapiens 87-91 21718937-4 2011 METHODS: DOTA-conjugated bisphosphonate (DOTA-Bn-SCN-HBP) was synthesized by conjugation of 2-(4-isothiocyanatebenzyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid to 4-amino-1-hydroxybutylidene-1,1-bisphosphonate (alendronate). Diphosphonates 25-39 heme binding protein 1 Homo sapiens 53-56 21445714-2 2011 In the same patients, bisphosphonates are reported to be effective on bone resorption but less effective on calcium and PTH excess. Diphosphonates 22-37 parathyroid hormone Homo sapiens 120-123 21455736-2 2011 The objective of the current study was to determine whether treatment with a bisphosphonate (risedronate, Ris), which reduces fractures in postmenopausal as well as in juvenile osteoporosis, was able to improve bone quality and reduce vertebral fractures in mice overexpressing Runx2. Diphosphonates 77-91 runt related transcription factor 2 Mus musculus 278-283 21240683-5 2011 Both bisphosphonates similarly decreased the bone marker B-ALP at 1 month (ZOL 24.7%, 95% CI 3.6-39.5%, and IBA 24.2%, 95% CI 2.8-43.4%) and 3 months (ZOL 28.6%, 95% CI +2.8-43.3%, and IBA 24.2%, 95% CI 3.2-47.4%). Diphosphonates 5-20 alkaline phosphatase, placental Homo sapiens 59-62 21420384-1 2011 A class of drugs successfully used for treatment of metabolic bone diseases is the nitrogen-containing bisphosphonates (N-BPs), which act by inhibiting the vital enzyme, farnesyl pyrophosphate synthase (FPPS), of the mevalonate pathway. Diphosphonates 103-118 farnesyl diphosphate synthase Homo sapiens 170-201 21424111-0 2011 Activated protein C inhibits bisphosphonate-induced endothelial cell death via the endothelial protein C receptor and nuclear factor-kappaB pathways. Diphosphonates 29-43 protein C receptor Homo sapiens 83-113 21424111-0 2011 Activated protein C inhibits bisphosphonate-induced endothelial cell death via the endothelial protein C receptor and nuclear factor-kappaB pathways. Diphosphonates 29-43 nuclear factor kappa B subunit 1 Homo sapiens 118-139 21424111-5 2011 Bisphosphonates markedly induced caspase-3 activaion, which was diminished in cells exposed to APC. Diphosphonates 0-15 caspase 3 Homo sapiens 33-42 21424111-6 2011 Matrix metalloproteinase-2 (MMP-2) reduction and nuclear factor-kappaB (NF-kappaB) activation induced by bisphosphonates in HUVECs were also blocked by APC treatment. Diphosphonates 105-120 matrix metallopeptidase 2 Homo sapiens 0-26 21424111-6 2011 Matrix metalloproteinase-2 (MMP-2) reduction and nuclear factor-kappaB (NF-kappaB) activation induced by bisphosphonates in HUVECs were also blocked by APC treatment. Diphosphonates 105-120 matrix metallopeptidase 2 Homo sapiens 28-33 21424111-6 2011 Matrix metalloproteinase-2 (MMP-2) reduction and nuclear factor-kappaB (NF-kappaB) activation induced by bisphosphonates in HUVECs were also blocked by APC treatment. Diphosphonates 105-120 nuclear factor kappa B subunit 1 Homo sapiens 49-70 21424111-6 2011 Matrix metalloproteinase-2 (MMP-2) reduction and nuclear factor-kappaB (NF-kappaB) activation induced by bisphosphonates in HUVECs were also blocked by APC treatment. Diphosphonates 105-120 nuclear factor kappa B subunit 1 Homo sapiens 72-81 21424111-8 2011 In conclusion, the present study demonstrates that APC inhibits bisphosphonate-induced endothelial cell death via EPCR-induced inactivation of caspase-3 and NF-kappaB, and also suggests that APC has the potential to be a therapeutic drug in various vascular diseases induced by endothelial cell damage. Diphosphonates 64-78 protein C receptor Homo sapiens 114-118 21424111-8 2011 In conclusion, the present study demonstrates that APC inhibits bisphosphonate-induced endothelial cell death via EPCR-induced inactivation of caspase-3 and NF-kappaB, and also suggests that APC has the potential to be a therapeutic drug in various vascular diseases induced by endothelial cell damage. Diphosphonates 64-78 caspase 3 Homo sapiens 143-152 21424111-8 2011 In conclusion, the present study demonstrates that APC inhibits bisphosphonate-induced endothelial cell death via EPCR-induced inactivation of caspase-3 and NF-kappaB, and also suggests that APC has the potential to be a therapeutic drug in various vascular diseases induced by endothelial cell damage. Diphosphonates 64-78 nuclear factor kappa B subunit 1 Homo sapiens 157-166 20972686-4 2011 In our patient with NSHPT, early bisphosphonate therapy was crucial in counteracting the marked hypercalcemia and allowed for safe surgical intervention ("total" parathyroidectomy, "thymectomy and hemithyroidectomy") at 3 months of age. Diphosphonates 33-47 calcium sensing receptor Homo sapiens 20-25 21366807-0 2011 Msx-1 is suppressed in bisphosphonate-exposed jaw bone analysis of bone turnover-related cell signalling after bisphosphonate treatment. Diphosphonates 23-37 msh homeobox 1 Homo sapiens 0-5 21366807-0 2011 Msx-1 is suppressed in bisphosphonate-exposed jaw bone analysis of bone turnover-related cell signalling after bisphosphonate treatment. Diphosphonates 111-125 msh homeobox 1 Homo sapiens 0-5 21366807-5 2011 Msx-1 expression might be impaired in bisphosphonate-related ONJ. Diphosphonates 38-52 msh homeobox 1 Homo sapiens 0-5 21366807-11 2011 CONCLUSIONS: Msx-1, RANKL suppression and BMP-2 induction were consistent with the bisphosphonate-associated osteopetrosis and impaired bone remodelling in BP- and aRANKL-induced ONJ. Diphosphonates 83-97 bone morphogenetic protein 2 Homo sapiens 42-47 21421837-7 2011 Inhibition of the osteoclast activity with bisphosphonate therapy blocked the Epo-induced bone loss. Diphosphonates 43-57 erythropoietin Mus musculus 78-81 21421837-8 2011 Intriguingly, bisphosphonate treatment also reduced the magnitude of the erythroid response to Epo. Diphosphonates 14-28 erythropoietin Mus musculus 95-98 22679450-7 2011 Thus, the preservation of the viability of osteoblasts and osteocytes by the anti-osteoporotic drugs bisphosphonates depends on Cx43 expression in vitro and in vivo. Diphosphonates 101-116 gap junction protein, alpha 1 Mus musculus 128-132 21465521-6 2011 Further studies show that bisphosphonates inhibit farnesyl pyrophosphate synthase, a critical enzyme required for synthesis of isoprenyl and geranylgeranyl, and inhibit prenylation and geranylgeranylation of small G-proteins such as Rac and Rho. Diphosphonates 26-41 farnesyl diphosphate synthase Homo sapiens 50-81 21335425-3 2011 We hypothesized that inhibition of farnesyl diphosphate synthase (FDPS) and geranylgeranyl diphosphate synthase (GGDPS) by bisphosphonates would induce autophagy by depleting cellular geranylgeranyl diphosphate (GGPP) and impairing protein geranylgeranylation. Diphosphonates 123-138 farnesyl diphosphate synthase Homo sapiens 35-64 21335425-3 2011 We hypothesized that inhibition of farnesyl diphosphate synthase (FDPS) and geranylgeranyl diphosphate synthase (GGDPS) by bisphosphonates would induce autophagy by depleting cellular geranylgeranyl diphosphate (GGPP) and impairing protein geranylgeranylation. Diphosphonates 123-138 farnesyl diphosphate synthase Homo sapiens 66-70 21420384-1 2011 A class of drugs successfully used for treatment of metabolic bone diseases is the nitrogen-containing bisphosphonates (N-BPs), which act by inhibiting the vital enzyme, farnesyl pyrophosphate synthase (FPPS), of the mevalonate pathway. Diphosphonates 103-118 farnesyl diphosphate synthase Homo sapiens 203-207 21082127-0 2011 P1,P2-diimidazolyl derivatives of pyrophosphate and bis-phosphonates--synthesis, properties, and use in preparation of dinucleoside tetraphosphates and analogs. Diphosphonates 52-68 crystallin gamma F, pseudogene Homo sapiens 0-5 21145999-4 2011 The nitrogen-containing bisphosphonates, such as alendronate, act as inhibitors of farnesyl-pyrophosphate synthase, which leads to inhibition of the prenylation of many intracellular signaling proteins. Diphosphonates 24-39 farnesyl diphosphate synthase Homo sapiens 83-114 21167123-8 2011 These results provide new evidence on the existence of a BP target in osteoblastic cells, presumably a PTP, which may be involved in the stimulatory action of BPs on osteoblast proliferation. Diphosphonates 57-59 protein tyrosine phosphatase, non-receptor type 13 Rattus norvegicus 103-106 21367798-1 2011 BET 1: do bisphosphonates relieve pain caused by acute osteoporotic vertebral compression fractures? Diphosphonates 10-25 Bet1 golgi vesicular membrane trafficking protein Homo sapiens 0-5 21237288-6 2011 The nitrogen-containing bisphosphonates pamidronate and zoledronate specifically inhibit farnesyl pyrophosphate synthase indicated by the accumulation of IPP/DMAPP. Diphosphonates 24-39 farnesyl diphosphate synthase Homo sapiens 89-120 21297379-0 2011 Bisphosphonate enhances TRAIL sensitivity to human osteosarcoma cells via death receptor 5 upregulation. Diphosphonates 0-14 TNF superfamily member 10 Homo sapiens 24-29 21297379-0 2011 Bisphosphonate enhances TRAIL sensitivity to human osteosarcoma cells via death receptor 5 upregulation. Diphosphonates 0-14 TNF receptor superfamily member 10b Homo sapiens 74-90 21297379-4 2011 The purpose of this study was to determine the effects of bisphosphonates on TRAIL-resistant MG 63 human osteosarcoma cells. Diphosphonates 58-73 TNF superfamily member 10 Homo sapiens 77-82 21297379-5 2011 The cells showed no response to TRAIL alone; however, pre-treatment with bisphosphonates significantly increased TRAIL-mediated apoptosis and cellular activation of caspase-3. Diphosphonates 73-88 TNF superfamily member 10 Homo sapiens 113-118 21297379-5 2011 The cells showed no response to TRAIL alone; however, pre-treatment with bisphosphonates significantly increased TRAIL-mediated apoptosis and cellular activation of caspase-3. Diphosphonates 73-88 caspase 3 Homo sapiens 165-174 21297379-6 2011 Bisphosphonates significantly induced mRNA and protein expression of the TRAIL receptor, DR5. Diphosphonates 0-15 TNF superfamily member 10 Homo sapiens 73-78 21297379-6 2011 Bisphosphonates significantly induced mRNA and protein expression of the TRAIL receptor, DR5. Diphosphonates 0-15 TNF receptor superfamily member 10b Homo sapiens 89-92 21297379-7 2011 Bisphosphonates induced protein unprenylation in MG 63 cells; in addition, co-treatment with TRAIL also significantly increased protein unprenylation. Diphosphonates 0-15 TNF superfamily member 10 Homo sapiens 93-98 21297379-9 2011 This is the first study to demonstrate that bisphosphonates markedly enhanced TRAIL-induced apoptosis in human osteosarcoma cells. Diphosphonates 44-59 TNF superfamily member 10 Homo sapiens 78-83 21297379-10 2011 These findings suggest that bisphosphonates may be a new and effective anticancer treatment with TRAIL proteins for TRAIL-resistant cancer cells. Diphosphonates 28-43 TNF superfamily member 10 Homo sapiens 97-102 21297379-10 2011 These findings suggest that bisphosphonates may be a new and effective anticancer treatment with TRAIL proteins for TRAIL-resistant cancer cells. Diphosphonates 28-43 TNF superfamily member 10 Homo sapiens 116-121 21247791-3 2011 Nitrogen-containing bisphosphonates (N-BPs) are particularly able to inhibit pyrophosphate synthase (FPPS) in the mevalonate pathway (MVP). Diphosphonates 20-35 farnesyl diphosphate synthase Homo sapiens 101-105 24212635-1 2011 BACKGROUND: Bisphosphonates interfere with the mevalonate pathway and inhibit the prenylation of small GTP-binding proteins such as ras and rap. Diphosphonates 12-27 LDL receptor related protein associated protein 1 Homo sapiens 140-143 21299894-8 2011 The integrinavb3 and tenascin C gene expression was effected by bisphosphonates in a cell line dependent manner with decreased, respectively inconsistent gene expression levels over time. Diphosphonates 64-79 tenascin C Homo sapiens 21-31 21177067-4 2011 In this study we used the method of stabilizing FGF2 from proteolytic degradation to identify some bisphosphonates, namely clodronate and etidronate, which interact with FGF2. Diphosphonates 99-114 fibroblast growth factor 2 Homo sapiens 48-52 21131587-3 2011 Mice treated with bisphosphonates exhibited a decrease in proportion and absolute number of Lin(-)cKit(+)Sca1(+) Flk2(-) (LKS Flk2(-)) and long-term culture-initiating cells in bone marrow (BM). Diphosphonates 18-33 FMS-like tyrosine kinase 3 Mus musculus 113-120 21131587-3 2011 Mice treated with bisphosphonates exhibited a decrease in proportion and absolute number of Lin(-)cKit(+)Sca1(+) Flk2(-) (LKS Flk2(-)) and long-term culture-initiating cells in bone marrow (BM). Diphosphonates 18-33 FMS-like tyrosine kinase 3 Mus musculus 113-117 21177067-10 2011 Our results show for the first time that bisphosphonates I) interact with FGF2, II) reduce FGF2-activity and III) decrease the angiogenic potential of this growth factor. Diphosphonates 41-56 fibroblast growth factor 2 Homo sapiens 74-78 21177067-10 2011 Our results show for the first time that bisphosphonates I) interact with FGF2, II) reduce FGF2-activity and III) decrease the angiogenic potential of this growth factor. Diphosphonates 41-56 fibroblast growth factor 2 Homo sapiens 91-95 21177067-4 2011 In this study we used the method of stabilizing FGF2 from proteolytic degradation to identify some bisphosphonates, namely clodronate and etidronate, which interact with FGF2. Diphosphonates 99-114 fibroblast growth factor 2 Homo sapiens 170-174 20849994-8 2011 MDA-MB-231 CM prevented bisphosphonate-induced cleavage of caspase-3 and up-regulation of BIM. Diphosphonates 24-38 caspase 3 Mus musculus 59-68 20849994-11 2011 Our data suggest that factors produced by the metastatic breast cancer cells promote osteoclast survival and block the apoptotic effect of bisphosphonates in MCSF and PLC-dependent manner, potentially compromising bisphosphonate effectiveness in the bone metastasis setting. Diphosphonates 139-154 colony stimulating factor 1 (macrophage) Mus musculus 158-162 21237434-0 2011 Bisphosphonates inhibit phosphorylation of signal transducer and activator of transcription 3 and expression of suppressor of cytokine signaling 3: implications for their effects on innate immune function and osteoclastogenesis. Diphosphonates 0-15 signal transducer and activator of transcription 3 Mus musculus 43-93 20849994-11 2011 Our data suggest that factors produced by the metastatic breast cancer cells promote osteoclast survival and block the apoptotic effect of bisphosphonates in MCSF and PLC-dependent manner, potentially compromising bisphosphonate effectiveness in the bone metastasis setting. Diphosphonates 139-153 colony stimulating factor 1 (macrophage) Mus musculus 158-162 21237434-0 2011 Bisphosphonates inhibit phosphorylation of signal transducer and activator of transcription 3 and expression of suppressor of cytokine signaling 3: implications for their effects on innate immune function and osteoclastogenesis. Diphosphonates 0-15 suppressor of cytokine signaling 3 Mus musculus 112-146 21237434-1 2011 OBJECTIVE: This study tested the effects of bisphosphonates (BPs) on the suppressor of cytokine signaling 3 (SOCS3) protein in macrophages. Diphosphonates 44-59 suppressor of cytokine signaling 3 Mus musculus 73-107 21237434-1 2011 OBJECTIVE: This study tested the effects of bisphosphonates (BPs) on the suppressor of cytokine signaling 3 (SOCS3) protein in macrophages. Diphosphonates 44-59 suppressor of cytokine signaling 3 Mus musculus 109-114 21237434-1 2011 OBJECTIVE: This study tested the effects of bisphosphonates (BPs) on the suppressor of cytokine signaling 3 (SOCS3) protein in macrophages. Diphosphonates 61-64 suppressor of cytokine signaling 3 Mus musculus 73-107 21237434-1 2011 OBJECTIVE: This study tested the effects of bisphosphonates (BPs) on the suppressor of cytokine signaling 3 (SOCS3) protein in macrophages. Diphosphonates 61-64 suppressor of cytokine signaling 3 Mus musculus 109-114 21237434-2 2011 SOCS3 has been shown to regulate cell differentiation and survival; however, its potential role in mediating the effects of BPs has not been explored. Diphosphonates 124-127 suppressor of cytokine signaling 3 Mus musculus 0-5 21237434-8 2011 CONCLUSIONS: These data demonstrate that, in addition to their effects on macrophage viability, BPs can decrease STAT3 and SOCS3 expression, which are important modulators of immune responses and bone homeostasis. Diphosphonates 96-99 signal transducer and activator of transcription 3 Mus musculus 113-118 21237434-8 2011 CONCLUSIONS: These data demonstrate that, in addition to their effects on macrophage viability, BPs can decrease STAT3 and SOCS3 expression, which are important modulators of immune responses and bone homeostasis. Diphosphonates 96-99 suppressor of cytokine signaling 3 Mus musculus 123-128 21290152-10 2011 Mean ALP levels did not reveal significant change and stayed within the reference range (110-370 IU/l) during the total course of bisphosphonate treatment. Diphosphonates 130-144 alkaline phosphatase, placental Homo sapiens 5-8 21110804-6 2011 First, we summarize the interactions between ligands and proteins observed in N-BPs-FPPS complexes in the Protein Data Bank (PDB). Diphosphonates 80-83 farnesyl diphosphate synthase Homo sapiens 84-88 21196316-4 2011 To determine if a higher sensitivity to bisphosphonates could in part explain the development of ONJ, the segregation of A/C rs2297480 polymorphism of gene encoding for the farnesyl pyrophosphate synthase (FDPS) with ONJ was evaluated in a cohort of 68 Caucasian patients treated with zoledronic acid for multiple myeloma and metastatic mammary and prostate cancer. Diphosphonates 40-55 farnesyl diphosphate synthase Homo sapiens 173-204 20662073-6 2011 Fracture rates were extrapolated to the US female population treated with oral bisphosphonates by MPR category over this 8-year period. Diphosphonates 79-94 progesterone receptor membrane component 1 Homo sapiens 98-101 20662073-9 2011 Extrapolating to the US population of female bisphosphonate users, we estimate over 27.9 million person-years of bisphosphonate treatment with MPR 50% or greater and 144,670 fractures prevented. Diphosphonates 45-59 progesterone receptor membrane component 1 Homo sapiens 143-146 20662073-9 2011 Extrapolating to the US population of female bisphosphonate users, we estimate over 27.9 million person-years of bisphosphonate treatment with MPR 50% or greater and 144,670 fractures prevented. Diphosphonates 113-127 progesterone receptor membrane component 1 Homo sapiens 143-146 21424089-3 2011 The purpose of this study is to determine the influence of intramedular administration (at the hip bone) of bisphosphonates on the serum values of alkaline phosphatase, total Ca, Ca2+, proteins and serum osteocalcin in a lot of experience Wistar rats. Diphosphonates 108-123 bone gamma-carboxyglutamate protein Rattus norvegicus 204-215 21552192-6 2011 In fact, the patients treated with bisphosphonates had significantly lower levels both of pain and total ALP. Diphosphonates 35-50 ATHS Homo sapiens 105-108 21181649-2 2010 We hypothesised that the effects of bisphosphonates on BMP-induced bone anabolism would be dose dependent, and we aimed to test this in a small animal model. Diphosphonates 36-51 bone morphogenetic protein 1 Homo sapiens 55-58 21151627-1 2010 A single nucleotide polymorphism (SNP) in CYP2C8 (rs1934951), was previously identified in a genome-wide association study as a risk factor for the development of osteonecrosis of the jaw (ONJ) in patients receiving bisphosphonates (BPs) for multiple myeloma. Diphosphonates 216-231 cytochrome P450 family 2 subfamily C member 8 Homo sapiens 42-48 20726960-9 2010 Serum ALP and urinary DPD are sensitive in monitoring bisphosphonate treatment. Diphosphonates 54-68 alkaline phosphatase, placental Homo sapiens 6-9 22132028-9 2010 CONCLUSION: Based on these clinical data (primary healing in 6/8 cases) and prior pre-clinical findings, we propose that BP therapy may be helpful in preserving the BMP-induced bone formation by inhibiting the osteoclastic bone loss. Diphosphonates 121-123 bone morphogenetic protein 7 Homo sapiens 165-168 20353344-9 2010 The results showed that the electronic changes have ignorable effects, steric influence is important in some cases, but the lipophilicity parameter is the most significant factor in hAChE inhibition by bisphosphonates. Diphosphonates 202-217 acetylcholinesterase (Cartwright blood group) Homo sapiens 182-187 21145521-13 2010 CONCLUSIONS: In this retrospective study, it was found that treatment with oral bisphosphonates significantly increases BMD at the hip in postpolio patients. Diphosphonates 80-95 hedgehog interacting protein Homo sapiens 131-134 21151627-1 2010 A single nucleotide polymorphism (SNP) in CYP2C8 (rs1934951), was previously identified in a genome-wide association study as a risk factor for the development of osteonecrosis of the jaw (ONJ) in patients receiving bisphosphonates (BPs) for multiple myeloma. Diphosphonates 233-236 cytochrome P450 family 2 subfamily C member 8 Homo sapiens 42-48 20832326-2 2010 For example, the nitrogenous bisphosphonates zoledronate and risedronate inhibit the enzyme farnesyl diphosphate synthase while digeranyl bisphosphonate has been shown to inhibit the enzyme geranylgeranyl diphosphate synthase. Diphosphonates 29-44 farnesyl diphosphate synthase Homo sapiens 92-121 20456336-1 2010 OBJECTIVE: To determine whether increased bone loss and bone turnover during the first 6 months of therapy for prostate cancer with luteinizing hormone-releasing hormone (LHRH)-agonist therapy could be prevented by bisphosphonate therapy with risedronate 35 mg/week, as prostate cancer is commonly treated with LHRH agonists and this often leads to rapid bone loss within the first 6 months of therapy. Diphosphonates 215-229 gonadotropin releasing hormone 1 Homo sapiens 171-175 20977404-4 2010 The results of clinical studies of adjuvant treatment on early-stage hormone-receptor-positive breast-cancer patients under hormonal treatment - especially with the bisphosphonate zoledronic acid - caused excitement because they demonstrated an additive effect on decreasing disease relapses at bone or other sites. Diphosphonates 165-179 nuclear receptor subfamily 4 group A member 1 Homo sapiens 69-85 20533067-5 2010 Compared with other BPs, zoledronic acid (ZOL) has a higher affinity to bone mineral and is a stronger inhibitor of the enzyme farnesyl pyrophosphate synthase (the main target of nitrogen-containing BPs), properties that explain the prolonged effect of ZOL on bone turnover and render it a therapeutic option for JPD, similar to PDB. Diphosphonates 199-202 farnesyl diphosphate synthase Homo sapiens 127-158 20567965-0 2010 Development of a new ELISA for serum periostin: evaluation of growth-related changes and bisphosphonate treatment in mice. Diphosphonates 89-103 periostin, osteoblast specific factor Mus musculus 37-46 20942943-0 2010 Expression of Msx-1 is suppressed in bisphosphonate associated osteonecrosis related jaw tissue-etiopathology considerations respecting jaw developmental biology-related unique features. Diphosphonates 37-51 msh homeobox 1 Homo sapiens 14-19 20942943-4 2010 We hypothesised that Msx-1 expression might be impaired in bisphosphonate-related ONJ. Diphosphonates 59-73 msh homeobox 1 Homo sapiens 21-26 20942943-13 2010 Msx-1 suppression in ONJ-adjacent periodontal tissue suggested a bisphosphonate-related impairment in cellular differentiation that occurred exclusively jaw remodelling. Diphosphonates 65-79 msh homeobox 1 Homo sapiens 0-5 20801032-0 2010 Novel bisphosphonate inhibitors of the human farnesyl pyrophosphate synthase. Diphosphonates 6-20 farnesyl diphosphate synthase Homo sapiens 45-76 20801032-1 2010 A structure-based approach was pursued in designing novel bisphosphonate inhibitors of the human farnesyl pyrophosphate synthase (hFPPS). Diphosphonates 58-72 farnesyl diphosphate synthase Homo sapiens 97-128 20801032-1 2010 A structure-based approach was pursued in designing novel bisphosphonate inhibitors of the human farnesyl pyrophosphate synthase (hFPPS). Diphosphonates 58-72 farnesyl diphosphate synthase Homo sapiens 130-135 20567965-3 2010 We developed a new ELISA and studied changes of periostin levels both locally at the bone site and systemically in circulating blood during growth and after bisphosphonate-induced inhibition of bone remodeling in the mouse. Diphosphonates 157-171 periostin, osteoblast specific factor Mus musculus 48-57 20506157-0 2010 The increased expression of receptor activator of nuclear-kappaB ligand (RANKL) of multiple myeloma bone marrow stromal cells is inhibited by the bisphosphonate ibandronate. Diphosphonates 146-160 TNF superfamily member 11 Homo sapiens 73-78 20674404-0 2010 Predicting risk for bisphosphonate-related osteonecrosis of the jaws: CTX versus radiographic markers. Diphosphonates 20-34 cytochrome P450 family 27 subfamily A member 1 Homo sapiens 70-73 20519142-10 2010 These results strongly indicate that bcl-2 reduction in bisphosphonate-treated PC-3 cells is dependent on inhibition of the mevalonate pathway. Diphosphonates 56-70 BCL2 apoptosis regulator Homo sapiens 37-42 20519142-11 2010 The inhibitory effect of bisphosphonates on bcl-2 expression shown in prostate cancer cell line should be tested in animal experiments and clinical studies. Diphosphonates 25-40 BCL2 apoptosis regulator Homo sapiens 44-49 20554708-12 2010 Stepwise regression showed that APR was more common in non-Japanese Asians, younger subjects, and nonsteroidal antiinflammatory drug users and was less common in smokers, patients with diabetes, previous users of oral bisphosphonates, and Latin Americans (P < 0.05 for all). Diphosphonates 218-233 phorbol-12-myristate-13-acetate-induced protein 1 Homo sapiens 32-35 20221651-0 2010 High level of serum undercarboxylated osteocalcin in patients with incident fractures during bisphosphonate treatment. Diphosphonates 93-107 bone gamma-carboxyglutamate protein Homo sapiens 38-49 20506157-2 2010 In this work we analyzed RANKL expression in human bone marrow mesenchymal stromal cells and the effect of the bisphosphonate ibandronate on RANKL expression after IL-1beta activation of ERK pathway. Diphosphonates 111-125 TNF superfamily member 11 Homo sapiens 141-146 20506157-9 2010 Finally, the bisphosphonate ibandronate, that hindered activation of the MEK/ERK pathway significantly inhibited both basal and IL-1beta dependent RANKL expression by cells. Diphosphonates 13-27 mitogen-activated protein kinase kinase 7 Homo sapiens 73-76 20506157-9 2010 Finally, the bisphosphonate ibandronate, that hindered activation of the MEK/ERK pathway significantly inhibited both basal and IL-1beta dependent RANKL expression by cells. Diphosphonates 13-27 mitogen-activated protein kinase 1 Homo sapiens 77-80 20506157-9 2010 Finally, the bisphosphonate ibandronate, that hindered activation of the MEK/ERK pathway significantly inhibited both basal and IL-1beta dependent RANKL expression by cells. Diphosphonates 13-27 interleukin 1 beta Homo sapiens 128-136 20506157-9 2010 Finally, the bisphosphonate ibandronate, that hindered activation of the MEK/ERK pathway significantly inhibited both basal and IL-1beta dependent RANKL expression by cells. Diphosphonates 13-27 TNF superfamily member 11 Homo sapiens 147-152 21472328-8 2010 Hypoxia prevented BP-induced cell damage by blocking JNK phosphorylation and by regulating the BCL-xL protein. Diphosphonates 18-20 mitogen-activated protein kinase 8 Homo sapiens 53-56 20711197-1 2010 Bisphosphonates are potent inhibitors of farnesyl pyrophosphate synthase (FPPS) and are highly efficacious in the treatment of bone diseases such as osteoporosis, Paget"s disease and tumor-induced osteolysis. Diphosphonates 0-15 farnesyl diphosphate synthase Homo sapiens 41-72 20711197-1 2010 Bisphosphonates are potent inhibitors of farnesyl pyrophosphate synthase (FPPS) and are highly efficacious in the treatment of bone diseases such as osteoporosis, Paget"s disease and tumor-induced osteolysis. Diphosphonates 0-15 farnesyl diphosphate synthase Homo sapiens 74-78 21472328-8 2010 Hypoxia prevented BP-induced cell damage by blocking JNK phosphorylation and by regulating the BCL-xL protein. Diphosphonates 18-20 BCL2 like 1 Homo sapiens 95-101 20549197-0 2010 Bisphosphonate inhibits bone turnover in OPG(-/-) mice via a depressive effect on both osteoclasts and osteoblasts. Diphosphonates 0-14 tumor necrosis factor receptor superfamily, member 11b (osteoprotegerin) Mus musculus 41-44 20544107-2 2010 We synthesized and studied a new type of nitrogen-containing bisphosphonate analogs and developed a sensitive end point assay method for enzyme FPPS, which was used for inhibitor screening. Diphosphonates 61-75 farnesyl diphosphate synthase Homo sapiens 144-148 20544107-3 2010 One potent FPPS inhibitor was discovered, and the structure-activity relationship of bisphosphonates for the enzyme inactivation was studied. Diphosphonates 85-100 farnesyl diphosphate synthase Homo sapiens 11-15 20549197-6 2010 However, administration of BP to OPG(-/-) mice reduced tooth movement distance, increased bone volume at the interradicular septum, decreased the osteoclast count, and reduced serum ALP. Diphosphonates 27-29 tumor necrosis factor receptor superfamily, member 11b (osteoprotegerin) Mus musculus 33-36 20549197-7 2010 BP administration also caused a temporal shift in peak Runx2 staining in OPG(-/-) mice, such that the overall staining time course was similar to that observed for WT mice. Diphosphonates 0-2 runt related transcription factor 2 Mus musculus 55-60 20549197-7 2010 BP administration also caused a temporal shift in peak Runx2 staining in OPG(-/-) mice, such that the overall staining time course was similar to that observed for WT mice. Diphosphonates 0-2 tumor necrosis factor receptor superfamily, member 11b (osteoprotegerin) Mus musculus 73-76 20549197-8 2010 We conclude that BP administration not only inhibited osteoclast activity in OPG(-/-) mice but also systemically and locally inhibited osteoblast activity. Diphosphonates 17-19 tumor necrosis factor receptor superfamily, member 11b (osteoprotegerin) Mus musculus 77-80 20618968-2 2010 In terms of side effects, they are known to be associated with osteonecrosis of the jaw (BONJ).The objective of this study was to evaluate the effect of bisphosphonates on osteoblast proliferation by cell count and gene expression analysis of cyclin D1 in vitro. Diphosphonates 153-168 cyclin D1 Homo sapiens 243-252 20450493-2 2010 FDPS is also the molecular target of nitrogen-containing bisphosphonates, which are used as bone-antiresorptive drugs in various disorders. Diphosphonates 57-72 farnesyl diphosphate synthase Homo sapiens 0-4 20567009-7 2010 After 7.8 mean years of follow-up (standard deviation, 1.7), invasive breast cancer incidence was lower in bisphosphonate users (hazard ratio [HR], 0.68; 95% CI, 0.52 to 0.88; P < .01) as was incidence of estrogen receptor (ER) -positive invasive cancers (HR, 0.70; 95% CI, 0.52 to 0.94, P = .02). Diphosphonates 107-121 estrogen receptor 1 Homo sapiens 208-225 20567009-7 2010 After 7.8 mean years of follow-up (standard deviation, 1.7), invasive breast cancer incidence was lower in bisphosphonate users (hazard ratio [HR], 0.68; 95% CI, 0.52 to 0.88; P < .01) as was incidence of estrogen receptor (ER) -positive invasive cancers (HR, 0.70; 95% CI, 0.52 to 0.94, P = .02). Diphosphonates 107-121 estrogen receptor 1 Homo sapiens 227-229 20051297-10 2010 Meta-analysis revealed that serious atrial fibrillation occurred more frequently in the bisphosphonate group compared to the placebo group (RR 1.525; 95% CI, 1.166 to 1.997; p=0.002). Diphosphonates 88-102 ribonucleotide reductase catalytic subunit M1 Homo sapiens 140-144 20299227-5 2010 Unlike most nitrogen-containing bisphosphonates which target farnesyl pyrophosphate synthase, experimental and theoretical investigations suggest that the activity of our derivatives may be related to different mechanisms. Diphosphonates 32-47 farnesyl diphosphate synthase Homo sapiens 61-92 20539033-3 2010 At the molecular level, bisphosphonates exert their anti-resorptive effects by inhibiting farnesyl pyrophosphate synthase activity within osteoclasts. Diphosphonates 24-39 farnesyl diphosphate synthase Homo sapiens 90-121 21472253-4 2010 BIS inhibit VEGF responses in endothelial cells. Diphosphonates 0-3 vascular endothelial growth factor A Homo sapiens 12-16 19577359-7 2010 In conclusion, zoledronic acid enhanced the TRAIL-to-OPG ratio in TRAIL-sensitive MDA-MB-231 cells, indicating that the TRAIL/OPG cytokine system is a bisphosphonate-responsive target in breast cancer. Diphosphonates 151-165 TNF superfamily member 10 Homo sapiens 44-49 20138570-8 2010 The mean ratio of the MBT in cancer patients with BP use over non-users was 0.88 (95% CI 0.80-0.96; p=0.003), and 0.83 (95% CI 0.73-0.94; p=0.001) when BP using oncological patients were compared with controls without malignancy or BP use. Diphosphonates 50-52 proteinase 3 Homo sapiens 22-25 20138570-9 2010 The ratio of MBT"s between BP naive patients was 0.95 (95% CI 0.83-1.07; p=0.8). Diphosphonates 27-29 proteinase 3 Homo sapiens 13-16 20191015-2 2010 The purpose of the present study is to investigate whether genetic polymorphisms of farnesyl diphosphate synthase (FDPS) or geranylgeranyl diphosphate synthase (GGPS) genes were associated with the response to bisphosphonate therapy. Diphosphonates 210-224 farnesyl diphosphate synthase Homo sapiens 84-113 20191015-2 2010 The purpose of the present study is to investigate whether genetic polymorphisms of farnesyl diphosphate synthase (FDPS) or geranylgeranyl diphosphate synthase (GGPS) genes were associated with the response to bisphosphonate therapy. Diphosphonates 210-224 farnesyl diphosphate synthase Homo sapiens 115-119 20191015-8 2010 Women with 2 deletion allele of GGPS1 -8188A ins/del had 7-fold higher risk of non-response to bisphosphonate therapy compared with women with other genotypes in GGPS1 -8188 after adjusting for baseline BMD (OR = 7.48; 95% CI = 1.32-42.30; p = 0.023). Diphosphonates 95-109 geranylgeranyl diphosphate synthase 1 Homo sapiens 32-37 20191015-10 2010 CONCLUSION: Our study suggested that GGPS1 -8188A ins/del polymorphism may confer susceptibility to femoral neck BMD response to bisphosphonate therapy in Korean women. Diphosphonates 129-143 geranylgeranyl diphosphate synthase 1 Homo sapiens 37-42 19903468-7 2010 Urokinase-type plasminogen activator (uPA) is one of the critical proteins in tumor metastasis and decreased in bisphosphonate-treated PC-3 cells. Diphosphonates 112-126 plasminogen activator, urokinase Homo sapiens 0-36 19903468-7 2010 Urokinase-type plasminogen activator (uPA) is one of the critical proteins in tumor metastasis and decreased in bisphosphonate-treated PC-3 cells. Diphosphonates 112-126 plasminogen activator, urokinase Homo sapiens 38-41 19903468-8 2010 We also showed that uPA expression was suppressed by PKC inhibitors (calphostin C and staurosporine) and induced by a PKC activator (PMA) in PC-3 cells, suggesting that the inhibition of uPA by bisphosphonates is involved in PKC inhibition. Diphosphonates 194-209 plasminogen activator, urokinase Homo sapiens 20-23 19903468-8 2010 We also showed that uPA expression was suppressed by PKC inhibitors (calphostin C and staurosporine) and induced by a PKC activator (PMA) in PC-3 cells, suggesting that the inhibition of uPA by bisphosphonates is involved in PKC inhibition. Diphosphonates 194-209 plasminogen activator, urokinase Homo sapiens 187-190 19903468-9 2010 This is the first finding that bisphosphonates suppress PKC expression in cancer cells. Diphosphonates 31-46 proline rich transmembrane protein 2 Homo sapiens 56-59 19903468-10 2010 These results strongly suggest that one of the mechanisms behind the inhibitory effect of bisphosphonates on tumor bone metastasis is mediated by PKC inhibition. Diphosphonates 90-105 proline rich transmembrane protein 2 Homo sapiens 146-149 20147814-5 2010 Recently, in oral and maxillofacial surgery, it was proposed that the levels of serum CTX may predict the subsequent risk of developing osteonecrosis of the jaws (ONJ) after oral surgery procedures for patients taking oral bisphosphonates (BPs). Diphosphonates 223-238 cytochrome P450 family 27 subfamily A member 1 Homo sapiens 86-89 20147814-5 2010 Recently, in oral and maxillofacial surgery, it was proposed that the levels of serum CTX may predict the subsequent risk of developing osteonecrosis of the jaws (ONJ) after oral surgery procedures for patients taking oral bisphosphonates (BPs). Diphosphonates 240-243 cytochrome P450 family 27 subfamily A member 1 Homo sapiens 86-89 21638970-5 2010 The aim of this study is to evaluate the expression of VEGF in bone marrow cells and the number of blood vessels and area occupied by them in animals treated with the BP sodium olpadronate (OPD). Diphosphonates 167-169 vascular endothelial growth factor A Rattus norvegicus 55-59 19836866-2 2010 Recently anti-RANKL agents (receptor activator of nuclear factor-kappaB ligand) such as denosumab (Prolia, Amgen Inc., California, USA) that have a similar mode of action to bisphosphonates have been introduced to treat such diseases. Diphosphonates 174-189 TNF superfamily member 11 Homo sapiens 14-19 19836866-2 2010 Recently anti-RANKL agents (receptor activator of nuclear factor-kappaB ligand) such as denosumab (Prolia, Amgen Inc., California, USA) that have a similar mode of action to bisphosphonates have been introduced to treat such diseases. Diphosphonates 174-189 TNF superfamily member 11 Homo sapiens 28-78 19819230-3 2010 FPPS inhibition leads also to the accumulation of isopentenyl pyrophosphate (IPP) and the apoptotic ATP analog, ApppI, but the role of this mechanism in the cytotoxic action of bisphosphonates is less clear. Diphosphonates 177-192 farnesyl diphosphate synthase Homo sapiens 0-4 19903468-0 2010 Protein kinase C is inhibited by bisphosphonates in prostate cancer PC-3 cells. Diphosphonates 33-48 proline rich transmembrane protein 2 Homo sapiens 0-16 19903468-2 2010 Since protein kinase C (PKC) plays a crucial role in cancer progression, we examined the effect of bisphosphonates on PKC expression to clarify the mechanism behind the inhibition of the bone metastasis of prostate cancer by bisphosphonates. Diphosphonates 99-114 proline rich transmembrane protein 2 Homo sapiens 118-121 20124800-0 2010 Bisphosphonate-induced TRAM flap fat necrosis. Diphosphonates 0-14 translocation associated membrane protein 1 Homo sapiens 23-27 20090316-4 2010 Furthermore, bisphosphonates accumulate in bone, inhibit osteoclasts, and may cause or exacerbate low-turnover (adynamic) bone disease - particularly in patients presenting with low parathyroid hormone (PTH) levels or receiving treatment for secondary hyperparathyroidism. Diphosphonates 13-28 parathyroid hormone Homo sapiens 182-201 19577359-7 2010 In conclusion, zoledronic acid enhanced the TRAIL-to-OPG ratio in TRAIL-sensitive MDA-MB-231 cells, indicating that the TRAIL/OPG cytokine system is a bisphosphonate-responsive target in breast cancer. Diphosphonates 151-165 TNF receptor superfamily member 11b Homo sapiens 53-56 19577359-7 2010 In conclusion, zoledronic acid enhanced the TRAIL-to-OPG ratio in TRAIL-sensitive MDA-MB-231 cells, indicating that the TRAIL/OPG cytokine system is a bisphosphonate-responsive target in breast cancer. Diphosphonates 151-165 TNF superfamily member 10 Homo sapiens 66-71 19577359-7 2010 In conclusion, zoledronic acid enhanced the TRAIL-to-OPG ratio in TRAIL-sensitive MDA-MB-231 cells, indicating that the TRAIL/OPG cytokine system is a bisphosphonate-responsive target in breast cancer. Diphosphonates 151-165 TNF superfamily member 10 Homo sapiens 66-71 19577359-7 2010 In conclusion, zoledronic acid enhanced the TRAIL-to-OPG ratio in TRAIL-sensitive MDA-MB-231 cells, indicating that the TRAIL/OPG cytokine system is a bisphosphonate-responsive target in breast cancer. Diphosphonates 151-165 TNF receptor superfamily member 11b Homo sapiens 126-129 19580457-4 2010 The intensive group received repeat courses of bisphosphonates irrespective of symptoms with the aim of reducing and maintaining serum alkaline phosphatase (ALP) levels within the normal range. Diphosphonates 47-62 alkaline phosphatase, placental Homo sapiens 135-155 20722616-3 2010 The simple bisphosphonates, clodronate, etidronate and tiludronate, are intracellularly metabolised to cytotoxic ATP analogues, while the more potent, nitrogen-containing bisphosphonates act by inhibiting the enzyme FPP synthase, thereby preventing the prenylation of small GTPases that are necessary for the normal function and survival of osteoclasts. Diphosphonates 11-26 farnesyl diphosphate synthase Homo sapiens 216-228 20722616-3 2010 The simple bisphosphonates, clodronate, etidronate and tiludronate, are intracellularly metabolised to cytotoxic ATP analogues, while the more potent, nitrogen-containing bisphosphonates act by inhibiting the enzyme FPP synthase, thereby preventing the prenylation of small GTPases that are necessary for the normal function and survival of osteoclasts. Diphosphonates 171-186 farnesyl diphosphate synthase Homo sapiens 216-228 19580457-4 2010 The intensive group received repeat courses of bisphosphonates irrespective of symptoms with the aim of reducing and maintaining serum alkaline phosphatase (ALP) levels within the normal range. Diphosphonates 47-62 alkaline phosphatase, placental Homo sapiens 157-160 21472217-2 2010 In the present study, we investigated the effect of minodronate, a newly developed bisphosphonate, on bFGF-induced VEGF synthesis in MC3T3-E1 cells. Diphosphonates 83-97 fibroblast growth factor 2 Mus musculus 102-106 19569175-7 2010 In addition, our results indicated that the inhibitory effects of bisphosphonates on the HIF-1alpha/VEGF axis are associated with the inhibition of the phosphoinositide 3-kinase/AKT/mammalian target of rapamycin signaling pathways. Diphosphonates 66-81 hypoxia inducible factor 1 subunit alpha Homo sapiens 89-99 19569175-7 2010 In addition, our results indicated that the inhibitory effects of bisphosphonates on the HIF-1alpha/VEGF axis are associated with the inhibition of the phosphoinositide 3-kinase/AKT/mammalian target of rapamycin signaling pathways. Diphosphonates 66-81 vascular endothelial growth factor A Homo sapiens 100-104 19569175-7 2010 In addition, our results indicated that the inhibitory effects of bisphosphonates on the HIF-1alpha/VEGF axis are associated with the inhibition of the phosphoinositide 3-kinase/AKT/mammalian target of rapamycin signaling pathways. Diphosphonates 66-81 AKT serine/threonine kinase 1 Homo sapiens 178-181 19569175-7 2010 In addition, our results indicated that the inhibitory effects of bisphosphonates on the HIF-1alpha/VEGF axis are associated with the inhibition of the phosphoinositide 3-kinase/AKT/mammalian target of rapamycin signaling pathways. Diphosphonates 66-81 mechanistic target of rapamycin kinase Homo sapiens 182-211 19569175-0 2010 Bisphosphonates suppress insulin-like growth factor 1-induced angiogenesis via the HIF-1alpha/VEGF signaling pathways in human breast cancer cells. Diphosphonates 0-15 insulin like growth factor 1 Homo sapiens 25-53 19569175-0 2010 Bisphosphonates suppress insulin-like growth factor 1-induced angiogenesis via the HIF-1alpha/VEGF signaling pathways in human breast cancer cells. Diphosphonates 0-15 hypoxia inducible factor 1 subunit alpha Homo sapiens 83-93 19569175-0 2010 Bisphosphonates suppress insulin-like growth factor 1-induced angiogenesis via the HIF-1alpha/VEGF signaling pathways in human breast cancer cells. Diphosphonates 0-15 vascular endothelial growth factor A Homo sapiens 94-98 19569175-3 2010 In this study, we investigated the potential molecular mechanisms underlying the antiangiogenic effect of non-nitrogen-containing and nitrogen-containing bisphosphonates, clodronate and pamidronate, respectively, in insulin-like growth factor (IGF)-1 responsive human breast cancer cells. Diphosphonates 154-169 insulin like growth factor 1 Homo sapiens 216-250 19574937-3 2010 The effects of bisphosphonate treatment in OPG-RANKL system have not been fully elucidated. Diphosphonates 15-29 TNF receptor superfamily member 11b Homo sapiens 43-46 19574937-3 2010 The effects of bisphosphonate treatment in OPG-RANKL system have not been fully elucidated. Diphosphonates 15-29 TNF superfamily member 11 Homo sapiens 47-52 19625131-10 2009 Experimental evidences demonstrated that bisphosphonates can inhibit capillary tube formation and vessel sprouting by impairing endothelial proliferation and migration, as well as reducing the serum fibroblast growth factor-2 and vascular endothelial growth factor. Diphosphonates 41-56 fibroblast growth factor 2 Homo sapiens 199-225 19925985-1 2009 PURPOSE: The aim of the present study was to correlate the staging of bisphosphonate-related osteonecrosis of the jaws (BRONJ) with serum C-terminal cross-linking telopeptide of type I collagen (CTX), which is under debate as an index of risk prediction. Diphosphonates 70-84 cytochrome P450 family 27 subfamily A member 1 Homo sapiens 178-199 19692118-9 2009 Moreover, the coatings synthesized from hydroxyapatite at relatively high bisphosphonate content (7.1% wt) displayed a reduced production of Tumour Necrosis Factor alpha (TNF-alpha) and Interleukin 6 (IL-6), suggesting a down-regulatory role of alendronate on the inflammatory reaction. Diphosphonates 74-88 tumor necrosis factor Homo sapiens 171-180 19692118-9 2009 Moreover, the coatings synthesized from hydroxyapatite at relatively high bisphosphonate content (7.1% wt) displayed a reduced production of Tumour Necrosis Factor alpha (TNF-alpha) and Interleukin 6 (IL-6), suggesting a down-regulatory role of alendronate on the inflammatory reaction. Diphosphonates 74-88 interleukin 6 Homo sapiens 186-199 19692118-9 2009 Moreover, the coatings synthesized from hydroxyapatite at relatively high bisphosphonate content (7.1% wt) displayed a reduced production of Tumour Necrosis Factor alpha (TNF-alpha) and Interleukin 6 (IL-6), suggesting a down-regulatory role of alendronate on the inflammatory reaction. Diphosphonates 74-88 interleukin 6 Homo sapiens 201-205 19665949-1 2009 Nitrogen-containing bisphosphonates (N-BPs) are shown to inhibit a key enzyme of intracellular mevalonate pathway, FPP synthase, leading to intracellular accumulation of pathway metabolites isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP). Diphosphonates 20-35 farnesyl diphosphate synthase Homo sapiens 115-127 19699819-4 2009 Nitrogen-containing bisphosphonates (N-BPs), including zoledronic acid (ZOL), act by inhibiting farnesyl pyrophosphate synthase (FPPS). Diphosphonates 20-35 farnesyl diphosphate synthase Homo sapiens 96-127 19699819-4 2009 Nitrogen-containing bisphosphonates (N-BPs), including zoledronic acid (ZOL), act by inhibiting farnesyl pyrophosphate synthase (FPPS). Diphosphonates 20-35 farnesyl diphosphate synthase Homo sapiens 129-133 19625131-10 2009 Experimental evidences demonstrated that bisphosphonates can inhibit capillary tube formation and vessel sprouting by impairing endothelial proliferation and migration, as well as reducing the serum fibroblast growth factor-2 and vascular endothelial growth factor. Diphosphonates 41-56 vascular endothelial growth factor A Homo sapiens 230-264 19834579-5 2009 Bisphosphonates are known to inhibit the mevalonate intracellular signaling pathway used by VEGF. Diphosphonates 0-15 vascular endothelial growth factor A Mus musculus 92-96 19834579-3 2009 To investigate whether the action of bisphosphonate on the growth plate works through VEGF, VEGF protein expression and isoform transcription in endochondral chondrocytes isolated from growing mice and treated with a clinically used bisphosphonate, alendronate, were assessed. Diphosphonates 37-51 vascular endothelial growth factor A Mus musculus 92-96 19361585-0 2009 Rho GTPase signaling and PTH 3-34, but not PTH 1-34, maintain the actin cytoskeleton and antagonize bisphosphonate effects in mouse osteoblastic MC3T3-E1 cells. Diphosphonates 100-114 parathyroid hormone Mus musculus 25-28 19810397-5 2009 The potency of the various nitrogen-containing bisphosphonates is dependent on a number of factors including bone binding, zeta potential and inhibition of the enzyme farnesyl pyrophosphate synthase. Diphosphonates 47-62 farnesyl diphosphate synthase Homo sapiens 167-198 19350555-0 2009 Activation of Src kinase by protein-tyrosine phosphatase-PEST in osteoclasts: comparative analysis of the effects of bisphosphonate and protein-tyrosine phosphatase inhibitor on Src activation in vitro. Diphosphonates 117-131 SRC proto-oncogene, non-receptor tyrosine kinase Homo sapiens 14-17 19350555-0 2009 Activation of Src kinase by protein-tyrosine phosphatase-PEST in osteoclasts: comparative analysis of the effects of bisphosphonate and protein-tyrosine phosphatase inhibitor on Src activation in vitro. Diphosphonates 117-131 SRC proto-oncogene, non-receptor tyrosine kinase Homo sapiens 178-181 19350555-7 2009 Treatment of osteoclasts with a bisphosphonate alendronate or a potent PTP inhibitor PAO decreased the activity and phosphorylation of Src at Y418 due to reduced dephosphorylation state at Y527. Diphosphonates 32-46 SRC proto-oncogene, non-receptor tyrosine kinase Homo sapiens 135-138 19350555-10 2009 We have shown that bisphosphonates could modulate the function of osteoclasts by inhibiting downstream signaling mediated by PTP-PEST/Src, in addition to its effect on the inhibition of the post-translational modification of small GTP-binding proteins such as Rab, Rho, and Rac as shown by others. Diphosphonates 19-34 protein tyrosine phosphatase non-receptor type 12 Homo sapiens 125-133 19350555-10 2009 We have shown that bisphosphonates could modulate the function of osteoclasts by inhibiting downstream signaling mediated by PTP-PEST/Src, in addition to its effect on the inhibition of the post-translational modification of small GTP-binding proteins such as Rab, Rho, and Rac as shown by others. Diphosphonates 19-34 SRC proto-oncogene, non-receptor tyrosine kinase Homo sapiens 134-137 19350555-10 2009 We have shown that bisphosphonates could modulate the function of osteoclasts by inhibiting downstream signaling mediated by PTP-PEST/Src, in addition to its effect on the inhibition of the post-translational modification of small GTP-binding proteins such as Rab, Rho, and Rac as shown by others. Diphosphonates 19-34 AKT serine/threonine kinase 1 Homo sapiens 274-277 19350555-11 2009 The promising effects of the inhibitors PP2 and PAO on osteoclast function suggest a therapeutic approach for patients with bone metastases and osteoporosis as an alternative to bisphosphonates. Diphosphonates 178-193 neuropeptide Y receptor Y6 (pseudogene) Homo sapiens 40-43 19597504-3 2009 Strong TGF-beta signaling in osteolytic bone lesions is suppressed directly by genetic and pharmacological disruption of the TGF-beta-SMAD pathway and indirectly by inhibition of osteoclast function with bisphosphonates. Diphosphonates 204-219 transforming growth factor beta 1 Homo sapiens 7-15 19721202-9 2009 ; (3) and Do estrogen and bisphosphonate, which reduce circulating osteocalcin, contribute to insulin resistance and obesity? Diphosphonates 26-40 bone gamma-carboxyglutamate protein 2 Mus musculus 67-78 19686941-0 2009 Bisphosphonate-induced avascular osteonecrosis of the mandible associated with a common thrombophilic mutation in the prothrombin gene. Diphosphonates 0-14 coagulation factor II, thrombin Homo sapiens 118-129 19371349-2 2009 Nitrogen-containing bisphosphonates (N-BPs), such as zoledronic acid, induce the formation of a novel ATP analogue (1-adenosin-5"-yl ester 3-(3-methylbut-3-enyl) ester triphosphoric acid; ApppI), as a consequence of the inhibition of farnesyl pyrophosphate synthase and the accumulation of isopentenyl pyrophosphate (IPP). Diphosphonates 20-35 farnesyl diphosphate synthase Homo sapiens 234-265 19265689-0 2009 The (mis) use of bone resorption markers in the context of bisphosphonate exposure, dental surgery and osteonecrosis of the jaw. Diphosphonates 59-73 anti-Mullerian hormone Homo sapiens 5-8 19233551-0 2009 Bisphosphonate zoledronic acid enhances the inhibitory effects of gefitinib on EGFR-mutated non-small cell lung carcinoma cells. Diphosphonates 0-14 epidermal growth factor receptor Homo sapiens 79-83 19233551-2 2009 Nitrogen-containing bisphosphonates (N-BPs) are inhibitors of farnesyl diphosphate (FPP) synthase as well as chelators of divalent cations. Diphosphonates 20-35 farnesyl diphosphate synthase Homo sapiens 62-97 19148563-2 2009 Previous studies have shown that polymorphisms of the LRP5 gene are associated with bone mineral density (BMD), but the relationship between LRP5 polymorphisms and response to bisphosphonate treatment in osteoporosis has not been studied. Diphosphonates 176-190 LDL receptor related protein 5 Homo sapiens 141-145 19505369-1 2009 OBJECTIVES: Nitrogen-containing bisphosphonates, which are widely used to treat osteoporosis, act as inhibitors of farnesyl pyrophosphate synthase, one of the key enzymes of the mevalonate pathway, and thus may have the potential to enhance the effect of statins (inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase). Diphosphonates 32-47 3-hydroxy-3-methylglutaryl-CoA reductase Rattus norvegicus 278-325 19454038-1 2009 BACKGROUND: This retrospective study evaluated, according to hormone receptor status, the antitumor effects of bisphosphonate especially on survival and disease progression in breast cancer patients with metastatic bone disease. Diphosphonates 111-125 nuclear receptor subfamily 4 group A member 1 Homo sapiens 61-77 19454038-4 2009 RESULTS: 87.8% of HR positive and 69.0% of HR negative patients received BPs with a median number of 17.7 cycles. Diphosphonates 73-76 nuclear receptor subfamily 4 group A member 1 Homo sapiens 43-45 19454038-5 2009 Although BPs treatment made no survival benefit in HR positive group, HR negative patients showed a significant prolonged survival when they received BPs treatment (hazard ratio = 0.56 [95% CI 0.34 to 0.91], P = 0.019). Diphosphonates 150-153 nuclear receptor subfamily 4 group A member 1 Homo sapiens 70-72 19454038-7 2009 CONCLUSION: Bisphosphonate treatment can result in a survival benefit in metastatic breast cancer patients with HR negative tumors. Diphosphonates 12-26 nuclear receptor subfamily 4 group A member 1 Homo sapiens 112-114 19398598-0 2009 Vascular endothelial growth factor activity after switching of bisphosphonate treatment for metastatic breast cancer. Diphosphonates 63-77 vascular endothelial growth factor A Homo sapiens 0-34 19398598-1 2009 BACKGROUND: Recent data have shown a fall in vascular endothelial growth factor (VEGF) concentrations after bisphosphonate (BP) treatment in BP-naive patients. Diphosphonates 108-122 vascular endothelial growth factor A Homo sapiens 45-79 19398598-1 2009 BACKGROUND: Recent data have shown a fall in vascular endothelial growth factor (VEGF) concentrations after bisphosphonate (BP) treatment in BP-naive patients. Diphosphonates 108-122 vascular endothelial growth factor A Homo sapiens 81-85 19398598-1 2009 BACKGROUND: Recent data have shown a fall in vascular endothelial growth factor (VEGF) concentrations after bisphosphonate (BP) treatment in BP-naive patients. Diphosphonates 124-126 vascular endothelial growth factor A Homo sapiens 45-79 19398598-1 2009 BACKGROUND: Recent data have shown a fall in vascular endothelial growth factor (VEGF) concentrations after bisphosphonate (BP) treatment in BP-naive patients. Diphosphonates 124-126 vascular endothelial growth factor A Homo sapiens 81-85 19398598-1 2009 BACKGROUND: Recent data have shown a fall in vascular endothelial growth factor (VEGF) concentrations after bisphosphonate (BP) treatment in BP-naive patients. Diphosphonates 141-143 vascular endothelial growth factor A Homo sapiens 45-79 19360288-13 2009 An increased expression of RANKL in stromal tissue surrounding bone metastases, RANK in osteoclasts and VEGF may serve as future targeted therapies possibly in conjunction with bisphosphonates. Diphosphonates 177-192 TNF superfamily member 11 Homo sapiens 27-32 19360288-13 2009 An increased expression of RANKL in stromal tissue surrounding bone metastases, RANK in osteoclasts and VEGF may serve as future targeted therapies possibly in conjunction with bisphosphonates. Diphosphonates 177-192 TNF receptor superfamily member 11a Homo sapiens 27-31 19360288-13 2009 An increased expression of RANKL in stromal tissue surrounding bone metastases, RANK in osteoclasts and VEGF may serve as future targeted therapies possibly in conjunction with bisphosphonates. Diphosphonates 177-192 vascular endothelial growth factor A Homo sapiens 104-108 19238075-4 2009 Bisphosphonate drugs such as zoledronic acid (Zol), used to treat bone diseases, have been shown to induce in vivo, in combination with interleukin-2, Vgamma9Vdelta2 T-cells" activation. Diphosphonates 0-14 interleukin 2 Homo sapiens 136-149 19059370-12 2009 In the bisphosphonate group, there was a child diagnosed with Apert syndrome, an autosomal dominant acrocephalosyndactyly, with a fibroblast growth factor 2 mutation. Diphosphonates 7-21 fibroblast growth factor 2 Homo sapiens 130-156 19398598-1 2009 BACKGROUND: Recent data have shown a fall in vascular endothelial growth factor (VEGF) concentrations after bisphosphonate (BP) treatment in BP-naive patients. Diphosphonates 141-143 vascular endothelial growth factor A Homo sapiens 81-85 19398598-3 2009 AIMS: To explore whether VEGF concentrations change after administration of a more potent BP in patients receiving long-term BP treatment. Diphosphonates 90-92 vascular endothelial growth factor A Homo sapiens 25-29 19398598-3 2009 AIMS: To explore whether VEGF concentrations change after administration of a more potent BP in patients receiving long-term BP treatment. Diphosphonates 125-127 vascular endothelial growth factor A Homo sapiens 25-29 19432105-4 2009 OPG-deficient mice exhibite high serum alkaline phosphatase activity and osteocalcin concentration, both of which are decreased to the levels of wild-type mice by the bisphosphonate injection. Diphosphonates 167-181 tumor necrosis factor receptor superfamily, member 11b (osteoprotegerin) Mus musculus 0-3 19432119-5 2009 After stopping bisphosphonates, PTH administration was effective to gain more BMD. Diphosphonates 15-30 parathyroid hormone Homo sapiens 32-35 19432119-6 2009 Sequential administration of antiresorber (bisphosphonate or raloxifene) and PTH could be more effective than the use of bisphosphonate alone. Diphosphonates 121-135 parathyroid hormone Homo sapiens 77-80 19432128-0 2009 [Effectiveness of bisphosphonate administration during Gn-RH agonist therapy for endometriosis]. Diphosphonates 18-32 gonadotropin releasing hormone 1 Homo sapiens 55-60 19432128-4 2009 In this review, the author shows the effect of bisphosphonate administration on the prevention of the bone loss during Gn-RH agonist therapy for the endometriosis. Diphosphonates 47-61 gonadotropin releasing hormone 1 Homo sapiens 119-124 19432128-7 2009 From these results, it is concluded that bisphosphonate administration has a beneficial effect for the prevention of the bone loss during Gn-RH agonist treatment. Diphosphonates 41-55 gonadotropin releasing hormone 1 Homo sapiens 138-143 19309137-0 2009 Lipophilic bisphosphonates as dual farnesyl/geranylgeranyl diphosphate synthase inhibitors: an X-ray and NMR investigation. Diphosphonates 11-26 geranylgeranyl diphosphate synthase 1 Homo sapiens 44-79 19309137-2 2009 Here, we report a new strategy for anticancer therapeutic agents involving inhibition of farnesyl diphosphate synthase (FPPS) and geranylgeranyl diphosphate synthase (GGPPS), the two enzymes upstream of FTase and GGTase, by lipophilic bisphosphonates. Diphosphonates 235-250 farnesyl diphosphate synthase Homo sapiens 89-118 19309137-2 2009 Here, we report a new strategy for anticancer therapeutic agents involving inhibition of farnesyl diphosphate synthase (FPPS) and geranylgeranyl diphosphate synthase (GGPPS), the two enzymes upstream of FTase and GGTase, by lipophilic bisphosphonates. Diphosphonates 235-250 farnesyl diphosphate synthase Homo sapiens 120-124 19309137-2 2009 Here, we report a new strategy for anticancer therapeutic agents involving inhibition of farnesyl diphosphate synthase (FPPS) and geranylgeranyl diphosphate synthase (GGPPS), the two enzymes upstream of FTase and GGTase, by lipophilic bisphosphonates. Diphosphonates 235-250 geranylgeranyl diphosphate synthase 1 Homo sapiens 130-165 19309137-2 2009 Here, we report a new strategy for anticancer therapeutic agents involving inhibition of farnesyl diphosphate synthase (FPPS) and geranylgeranyl diphosphate synthase (GGPPS), the two enzymes upstream of FTase and GGTase, by lipophilic bisphosphonates. Diphosphonates 235-250 geranylgeranyl diphosphate synthase 1 Homo sapiens 167-172 19231609-6 2009 Recombinant parathyroid hormone is reserved for patients who have failed or are not candidates for bisphosphonate therapy. Diphosphonates 99-113 parathyroid hormone Homo sapiens 12-31 19718808-0 2009 Improved bone delivery of osteoprotegerin by bisphosphonate conjugation in a rat model of osteoarthritis. Diphosphonates 45-59 TNF receptor superfamily member 11B Rattus norvegicus 26-41 19405951-0 2009 RANKL increases the level of Mcl-1 in osteoclasts and reduces bisphosphonate-induced osteoclast apoptosis in vitro. Diphosphonates 62-76 tumor necrosis factor (ligand) superfamily, member 11 Mus musculus 0-5 19217524-4 2009 [(90)Y]DOTA-complex-conjugated bisphosphonate ([(90)Y]DOTA-HBP) was prepared by coordination with (90)Y, and its biodistribution was studied in comparison to [(90)Y]citrate. Diphosphonates 31-45 heme binding protein 1 Homo sapiens 59-62 19405951-2 2009 We examined whether the ability of bisphosphonates to induce osteoclast apoptosis and inhibit bone resorption in vitro is influenced by the cytokine receptor activator of nuclear factor-kappa B ligand (RANKL), an important mediator of inflammation-induced bone loss. Diphosphonates 35-50 tumor necrosis factor (ligand) superfamily, member 11 Mus musculus 202-207 19405951-10 2009 CONCLUSIONS: RANKL protects osteoclasts from the apoptosis-inducing and anti-resorptive effects of bisphosphonates in vitro. Diphosphonates 99-114 tumor necrosis factor (ligand) superfamily, member 11 Mus musculus 13-18 19432497-1 2009 Clodronic acid (Cl(2)-MBP [dichloromethylene bisphosphonic acid], clodronate) is a halogenated non-nitrogen-containing bisphosphonate with antiresorptive efficacy in a variety of diseases associated with excessive bone resorption. Diphosphonates 119-133 myelin basic protein Homo sapiens 22-25 19016713-1 2009 Nitrogen-containing bisphosphonates indirectly activate Vgamma9Vdelta2 T cells through inhibition of farnesyl pyrophosphate synthase and intracellular accumulation of isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP), but the cells responsible for Vgamma9Vdelta2 T cell activation through IPP/DMAPP accumulation are unknown. Diphosphonates 20-35 farnesyl diphosphate synthase Homo sapiens 101-132 19070762-13 2009 CONCLUSIONS: We hypothesize that matrix metalloproteinase 2 (MMP2) is a candidate gene for bisphosphonate-induced ONJ for 3 reasons: 1) MMP2 is associated with bone abnormalities which could be related to ONJ. Diphosphonates 91-105 matrix metallopeptidase 2 Homo sapiens 33-59 19744312-6 2009 RESULTS: With this approach, we identified novel targets of nitrogen-containing bisphosphonates, such as tubulin cofactor B and ASK/DBF4 (Activator of S-phase kinase). Diphosphonates 80-95 protein serine/threonine kinase activating protein DBF4 Saccharomyces cerevisiae S288C 132-136 18715136-0 2009 Bisphosphonate therapy ameliorates hearing loss in mice lacking osteoprotegerin. Diphosphonates 0-14 tumor necrosis factor receptor superfamily, member 11b (osteoprotegerin) Mus musculus 64-79 19070762-13 2009 CONCLUSIONS: We hypothesize that matrix metalloproteinase 2 (MMP2) is a candidate gene for bisphosphonate-induced ONJ for 3 reasons: 1) MMP2 is associated with bone abnormalities which could be related to ONJ. Diphosphonates 91-105 matrix metallopeptidase 2 Homo sapiens 61-65 19070762-13 2009 CONCLUSIONS: We hypothesize that matrix metalloproteinase 2 (MMP2) is a candidate gene for bisphosphonate-induced ONJ for 3 reasons: 1) MMP2 is associated with bone abnormalities which could be related to ONJ. Diphosphonates 91-105 matrix metallopeptidase 2 Homo sapiens 136-140 19070762-15 2009 3) A network of disorders and disease genes linked by known disorder-gene associations indicates that cardiovascular disease and bone disease are closely related, suggesting that a single drug such as bisphosphonate, acting on a single gene, MMP2, could have both bone and cardiovascular side effects different from the osteoclast inhibition that is characteristic of bisphosphonate. Diphosphonates 201-215 matrix metallopeptidase 2 Homo sapiens 242-246 19070762-15 2009 3) A network of disorders and disease genes linked by known disorder-gene associations indicates that cardiovascular disease and bone disease are closely related, suggesting that a single drug such as bisphosphonate, acting on a single gene, MMP2, could have both bone and cardiovascular side effects different from the osteoclast inhibition that is characteristic of bisphosphonate. Diphosphonates 368-382 matrix metallopeptidase 2 Homo sapiens 242-246 18594024-0 2008 Bisphosphonate-related osteonecrosis of the jaw is associated with polymorphisms of the cytochrome P450 CYP2C8 in multiple myeloma: a genome-wide single nucleotide polymorphism analysis. Diphosphonates 0-14 cytochrome P450 family 2 subfamily C member 8 Homo sapiens 104-110 18637708-1 2009 Nitrogen-containing bisphosphonates were found to inhibit farnesyl diphosphate synthase - an essential enzyme in the cholesterol biosynthesis pathway, but their effect on cholesterol synthesis per se in the central nervous system (CNS) remains unknown. Diphosphonates 20-35 farnesyl diphosphate synthase Rattus norvegicus 58-87 18951870-5 2008 Depletion of macrophages by a bisphosphonate encapsulated in liposomes inhibited this IL-1beta-induced lymphangiogenesis and also up-regulation of VEGF-A, VEGF-C, and VEGF-D. Diphosphonates 30-44 interleukin 1 beta Mus musculus 86-94 18951870-5 2008 Depletion of macrophages by a bisphosphonate encapsulated in liposomes inhibited this IL-1beta-induced lymphangiogenesis and also up-regulation of VEGF-A, VEGF-C, and VEGF-D. Diphosphonates 30-44 vascular endothelial growth factor A Mus musculus 147-153 18951870-5 2008 Depletion of macrophages by a bisphosphonate encapsulated in liposomes inhibited this IL-1beta-induced lymphangiogenesis and also up-regulation of VEGF-A, VEGF-C, and VEGF-D. Diphosphonates 30-44 vascular endothelial growth factor C Mus musculus 155-161 18951870-5 2008 Depletion of macrophages by a bisphosphonate encapsulated in liposomes inhibited this IL-1beta-induced lymphangiogenesis and also up-regulation of VEGF-A, VEGF-C, and VEGF-D. Diphosphonates 30-44 vascular endothelial growth factor D Mus musculus 167-173 26816278-6 2008 Bisphosphonates are the compounds of choice for PDB therapy; these are readily available and have received approval. Diphosphonates 0-15 PDB1 Homo sapiens 48-51 19013390-0 2008 Numb chin syndrome by biphosphonates. Diphosphonates 22-36 NUMB endocytic adaptor protein Homo sapiens 0-4 18597631-0 2008 Connexin 43 is required for the anti-apoptotic effect of bisphosphonates on osteocytes and osteoblasts in vivo. Diphosphonates 57-72 gap junction protein, alpha 1 Mus musculus 0-11 18597631-9 2008 Taken together with earlier in vitro evidence, these findings show that Cx43 is required for the anti-apoptotic effect of bisphosphonates on osteocytes and osteoblasts. Diphosphonates 122-137 gap junction protein, alpha 3 Mus musculus 72-76 18442135-1 2008 We report the X-ray crystallographic structures of the bisphosphonate N-[methyl(4-phenylbutyl)]-3-aminopropyl-1-hydroxy-1,1-bisphosphonate (BPH-210), a potent analog of pamidronate (Aredia), bound to farnesyl diphosphate synthase (FPPS) from Trypanosoma brucei as well as to geranylgeranyl diphosphate synthase from Saccharomyces cerevisiae. Diphosphonates 55-69 farnesyl diphosphate synthase Homo sapiens 231-235 18442135-6 2008 In this case, the bisphosphonate binds only to the GGPP product inhibitory site, with only 1 (chain A) or 0 (chain B) Mg(2+), and DeltaS is much smaller and DeltaH is approximately 6 k cal more negative than in the case of FPPS binding. Diphosphonates 18-32 farnesyl diphosphate synthase Homo sapiens 223-227 18404739-2 2008 Because this difference has been attributed to the antiapoptotic inflammatory signals that protect osteoclasts from BP-induced apoptosis, but not RANK antagonists, we tested the hypothesis that osteoprotegerin (OPG) is more effective in preventing wear debris-induced osteolysis than zoledronic acid (ZA) or alendronate (Aln) in the murine calvaria model using in vivo micro-CT and traditional histology. Diphosphonates 116-118 tumor necrosis factor receptor superfamily, member 11b (osteoprotegerin) Mus musculus 194-209 18836673-0 2008 Clinical and biochemical response of TNFRSF11A-mediated early-onset familial Paget disease to bisphosphonate therapy. Diphosphonates 94-108 TNF receptor superfamily member 11a Homo sapiens 37-46 18775204-4 2008 Using the key words bisphosphonate and clinical practice in a PubMed literature search from January 1, 1998, to May 1, 2008, we review current understanding of the mechanisms by which bisphosphonates exert their effects on osteoclasts, discuss the role of bisphosphonates in clinical practice, and highlight some areas of concern associated with bisphosphonate use. Diphosphonates 184-199 protein kinase C delta Homo sapiens 112-117 18800762-2 2008 Bisphosphonates containing unbranched side chains bind to either the farnesyl diphosphate (FPP) substrate site, the geranylgeranyl diphosphate (GGPP) product site, and in one case, both sites, with the bisphosphonate moiety interacting with 3 Mg (2+) that occupy the same position as found in FPP synthase. Diphosphonates 0-15 farnesyl diphosphate synthase Homo sapiens 293-305 18800762-5 2008 Activities of the bisphosphonates in GGPPS inhibition were predicted with an overall error of 2x by using a comparative molecular similarity analysis based on a docked-structure alignment. Diphosphonates 18-33 geranylgeranyl diphosphate synthase 1 Homo sapiens 37-42 18775204-4 2008 Using the key words bisphosphonate and clinical practice in a PubMed literature search from January 1, 1998, to May 1, 2008, we review current understanding of the mechanisms by which bisphosphonates exert their effects on osteoclasts, discuss the role of bisphosphonates in clinical practice, and highlight some areas of concern associated with bisphosphonate use. Diphosphonates 184-198 protein kinase C delta Homo sapiens 112-117 18583139-4 2008 However, the bis(sulfonamide) analogues 6 and 8 substituted at the position 2 of adenine were approximately 3- to 10-fold less potent inhibitors of IMPDH2 (K(i)=0.3-0.4 microM) than the corresponding parent bis(phosphonate)s 2 and 3 (K(i)=0.04-0.11 microM), respectively. Diphosphonates 207-223 inosine monophosphate dehydrogenase 2 Homo sapiens 148-154 18214569-7 2008 The antiresorptive effects of the nitrogen-containing BPs (including alendronate, risedronate, ibandronate, and zoledronate) appear to result from their inhibition of the enzyme farnesyl pyrophosphate synthase (FPPS) in osteoclasts. Diphosphonates 54-57 farnesyl diphosphate synthase Homo sapiens 178-209 24692812-0 2008 A probable case of oral bisphosphonate-associated osteonecrosis of the jaw and recovery with parathyroid hormone treatment. Diphosphonates 24-38 parathyroid hormone Homo sapiens 93-112 18504149-6 2008 CONCLUSIONS: High concentrations of alendronate and zoledronate were cytotoxic, decreasing cell viability at 72 h. Transforming growth factor beta1 increased even as viability decreased, suggesting a mechanism for bisphosphonate action. Diphosphonates 214-228 transforming growth factor, beta 1 Rattus norvegicus 115-147 18463892-8 2008 This means that isoprenylation can be influenced by drugs such as statins, which inhibit isoprenylation, or biphosphonates, which inhibit that farnesyl pyrophosphate synthase necessary for Rab GTPase activity. Diphosphonates 108-122 farnesyl diphosphate synthase Homo sapiens 143-174 18463892-8 2008 This means that isoprenylation can be influenced by drugs such as statins, which inhibit isoprenylation, or biphosphonates, which inhibit that farnesyl pyrophosphate synthase necessary for Rab GTPase activity. Diphosphonates 108-122 ArfGAP with FG repeats 1 Homo sapiens 189-192 18214569-7 2008 The antiresorptive effects of the nitrogen-containing BPs (including alendronate, risedronate, ibandronate, and zoledronate) appear to result from their inhibition of the enzyme farnesyl pyrophosphate synthase (FPPS) in osteoclasts. Diphosphonates 54-57 farnesyl diphosphate synthase Homo sapiens 211-215 18327899-0 2008 Structure-activity relationships among the nitrogen containing bisphosphonates in clinical use and other analogues: time-dependent inhibition of human farnesyl pyrophosphate synthase. Diphosphonates 63-78 farnesyl diphosphate synthase Homo sapiens 151-182 18492387-13 2008 A prospective study should investigate if patients with CaR-positive tumours are more likely to develop bone metastases and whether they could benefit more from prophylactic treatment with bisphosphonates or the newly developed CaR antagonists. Diphosphonates 189-204 calcium sensing receptor Homo sapiens 56-59 18325729-0 2008 Preclinical evidence for nitrogen-containing bisphosphonate inhibition of farnesyl diphosphate (FPP) synthase in the kidney: implications for renal safety. Diphosphonates 45-59 farnesyl diphosphate synthase Rattus norvegicus 74-109 18325729-3 2008 Nitrogen-containing bisphosphonates directly inhibit farnesyl diphosphate (FPP) synthase activity (mevalonate pathway) and reduce protein prenylation leading to osteoclast cell death. Diphosphonates 20-35 farnesyl diphosphate synthase Rattus norvegicus 53-88 18391687-0 2008 Prior bisphosphonate therapy of osteoporosis attenuates and blocks response to subsequent parathyroid hormone. Diphosphonates 6-20 parathyroid hormone Homo sapiens 90-109 18454049-8 2008 The production of cytotoxic ATP analogs in tumor cells after BP treatment is likely to depend on the activity of enzymes, such as farnesyl diphosphate synthase or aminoacyl-tRNA synthetases, responsible for ATP analog formation. Diphosphonates 61-63 farnesyl diphosphate synthase Homo sapiens 130-159 18310769-0 2008 Bisphosphonates can block the deterioration in implant fixation after withdrawal of intermittent doses of parathyroid hormone. Diphosphonates 0-15 parathyroid hormone Rattus norvegicus 106-125 18431039-2 2008 TRK-530 is a novel synthetic bisphosphonate with an anti-oxidant methylthio-phenylthio side chain. Diphosphonates 29-43 neurotrophic receptor tyrosine kinase 1 Homo sapiens 0-3 18083724-14 2008 A significant increase in bisphosphonate prescription was seen in the intervention group over the control group (IRR = 1.50 [1.00, 2.24] P = 0.05). Diphosphonates 26-40 insulin receptor related receptor Homo sapiens 113-116 18473904-2 2008 Antiprotozoal properties of bisphosphonates, which target FPPS, have generated interest in FPPS as a potential antiprotozoal drug target. Diphosphonates 28-43 farnesyl diphosphate synthase Homo sapiens 58-62 18473904-2 2008 Antiprotozoal properties of bisphosphonates, which target FPPS, have generated interest in FPPS as a potential antiprotozoal drug target. Diphosphonates 28-43 farnesyl diphosphate synthase Homo sapiens 91-95 18283582-2 2008 This might be explained by the reduced number of remodeling sites after bisphosphonate treatment, which reduces the number of cells able to respond to PTH. Diphosphonates 72-86 parathyroid hormone Rattus norvegicus 151-154 18260178-10 2008 CONCLUSION: Vit K2 alone or in combination with bisphosphonates for treatment of osteoporosis in patients with RA may inhibit osteoclast induction via decreases in levels of RANKL. Diphosphonates 48-63 TNF superfamily member 11 Homo sapiens 174-179 18037402-3 2008 In the prostate cancer cell lines we investigated the effects on hTERT gene expression of several bisphosphonates. Diphosphonates 98-113 telomerase reverse transcriptase Homo sapiens 65-70 18183447-0 2008 Bisphosphonate treatment increases the size of the mandibular condyle and normalizes growth of the mandibular ramus in osteoprotegerin-deficient mice. Diphosphonates 0-14 tumor necrosis factor receptor superfamily, member 11b (osteoprotegerin) Mus musculus 119-134 17728092-12 2008 In conclusion Cystatin C and cathepsin K may be regarded as possible markers to monitor the therapeutic response to bisphosphonate treatments. Diphosphonates 116-130 cystatin C Homo sapiens 14-24 17728092-12 2008 In conclusion Cystatin C and cathepsin K may be regarded as possible markers to monitor the therapeutic response to bisphosphonate treatments. Diphosphonates 116-130 cathepsin K Homo sapiens 29-40 18183447-5 2008 All bone formation-related parameters and bone resorption-related parameters were significantly lower in OPG-/- mice with bisphosphonate than in those without bisphosphonate. Diphosphonates 122-136 tumor necrosis factor receptor superfamily, member 11b (osteoprotegerin) Mus musculus 105-108 18183447-9 2008 Histologically, the surface irregularity of the mandibular condyle that was observed in the OPG-/- mice without bisphosphonate tended to be less marked in the OPG-/- mice with bisphosphonate, and the proportion of the area of the cartilage layer relative to the whole condyle was significantly larger in OPG-/- mice with bisphosphonate than in those without bisphosphonate. Diphosphonates 176-190 tumor necrosis factor receptor superfamily, member 11b (osteoprotegerin) Mus musculus 159-162 18183447-9 2008 Histologically, the surface irregularity of the mandibular condyle that was observed in the OPG-/- mice without bisphosphonate tended to be less marked in the OPG-/- mice with bisphosphonate, and the proportion of the area of the cartilage layer relative to the whole condyle was significantly larger in OPG-/- mice with bisphosphonate than in those without bisphosphonate. Diphosphonates 176-190 tumor necrosis factor receptor superfamily, member 11b (osteoprotegerin) Mus musculus 159-162 18183447-7 2008 Bisphosphonate treatment of the OPG-/- mice resulted in an increase in the volume of the mandibular condyle and mandibular ramus length. Diphosphonates 0-14 tumor necrosis factor receptor superfamily, member 11b (osteoprotegerin) Mus musculus 32-35 18183447-9 2008 Histologically, the surface irregularity of the mandibular condyle that was observed in the OPG-/- mice without bisphosphonate tended to be less marked in the OPG-/- mice with bisphosphonate, and the proportion of the area of the cartilage layer relative to the whole condyle was significantly larger in OPG-/- mice with bisphosphonate than in those without bisphosphonate. Diphosphonates 176-190 tumor necrosis factor receptor superfamily, member 11b (osteoprotegerin) Mus musculus 159-162 18183447-9 2008 Histologically, the surface irregularity of the mandibular condyle that was observed in the OPG-/- mice without bisphosphonate tended to be less marked in the OPG-/- mice with bisphosphonate, and the proportion of the area of the cartilage layer relative to the whole condyle was significantly larger in OPG-/- mice with bisphosphonate than in those without bisphosphonate. Diphosphonates 176-190 tumor necrosis factor receptor superfamily, member 11b (osteoprotegerin) Mus musculus 159-162 18183447-8 2008 In fact, the mandibular ramus length in OPG-/- mice with bisphosphonate was similar to the length in WT mice without bisphosphonate. Diphosphonates 57-71 tumor necrosis factor receptor superfamily, member 11b (osteoprotegerin) Mus musculus 40-43 18183447-9 2008 Histologically, the surface irregularity of the mandibular condyle that was observed in the OPG-/- mice without bisphosphonate tended to be less marked in the OPG-/- mice with bisphosphonate, and the proportion of the area of the cartilage layer relative to the whole condyle was significantly larger in OPG-/- mice with bisphosphonate than in those without bisphosphonate. Diphosphonates 176-190 tumor necrosis factor receptor superfamily, member 11b (osteoprotegerin) Mus musculus 159-162 18077874-2 2007 METHODS: 64-year-old male with nine months history of disseminated prostate cancer, taking hormonal treatment and biphosphonates, who presents with rising PSA, facial dysesthesia and left exophtalmos. Diphosphonates 114-128 aminopeptidase puromycin sensitive Homo sapiens 155-158 18183447-9 2008 Histologically, the surface irregularity of the mandibular condyle that was observed in the OPG-/- mice without bisphosphonate tended to be less marked in the OPG-/- mice with bisphosphonate, and the proportion of the area of the cartilage layer relative to the whole condyle was significantly larger in OPG-/- mice with bisphosphonate than in those without bisphosphonate. Diphosphonates 176-190 tumor necrosis factor receptor superfamily, member 11b (osteoprotegerin) Mus musculus 159-162 17979996-0 2008 Nitrogen-containing bisphosphonate, YM529/ONO-5920, inhibits macrophage inflammatory protein 1 alpha expression and secretion in mouse myeloma cells. Diphosphonates 20-34 chemokine (C-C motif) ligand 3 Mus musculus 61-100 18219222-13 2008 Since the calcium-sensing receptor (CaSR) mutation was reported, the form of management in neonates has become more medical (intravenous diphosphonates) than surgical. Diphosphonates 137-151 calcium sensing receptor Homo sapiens 10-34 18219222-13 2008 Since the calcium-sensing receptor (CaSR) mutation was reported, the form of management in neonates has become more medical (intravenous diphosphonates) than surgical. Diphosphonates 137-151 calcium sensing receptor Homo sapiens 36-40 17787010-0 2008 Modeling bone morphogenetic protein and bisphosphonate combination therapy in wild-type and Nf1 haploinsufficient mice. Diphosphonates 40-54 neurofibromin 1 Mus musculus 92-95 17787010-3 2008 As abnormalities in both bone formation and resorption have been documented in Nf1-deficient mice, we hypothesized that inadequate BMP-induced bone formation could be augmented by cotreatment with the bisphosphonate zoledronic acid (ZA). Diphosphonates 201-215 neurofibromin 1 Mus musculus 79-82 17787010-3 2008 As abnormalities in both bone formation and resorption have been documented in Nf1-deficient mice, we hypothesized that inadequate BMP-induced bone formation could be augmented by cotreatment with the bisphosphonate zoledronic acid (ZA). Diphosphonates 201-215 bone morphogenetic protein 2 Mus musculus 131-134 17787010-11 2008 Bisphosphonate combination therapy is superior to BMP therapy alone in terms of net bone production in vivo in both wild-type and Nf1-deficient mice. Diphosphonates 0-14 neurofibromin 1 Mus musculus 130-133 18226993-9 2008 Our data suggest that bisphosphonates reduce TRACP 5b activity in the intertrochanteric area rather than in the anterior femoral head. Diphosphonates 22-37 acid phosphatase 5, tartrate resistant Homo sapiens 45-53 18022461-0 2007 Oral bisphosphonate-induced osteonecrosis: risk factors, prediction of risk using serum CTX testing, prevention, and treatment. Diphosphonates 5-19 cytochrome P450 family 27 subfamily A member 1 Homo sapiens 88-91 18022461-7 2007 The morning fasting serum C-terminal telopeptide (CTX) test results were observed to correlate to the duration of oral bisphosphonate use and could indicate a recovery of bone remodeling with increased values if the oral bisphosphonate was discontinued. Diphosphonates 119-133 cytochrome P450 family 27 subfamily A member 1 Homo sapiens 50-53 18022461-7 2007 The morning fasting serum C-terminal telopeptide (CTX) test results were observed to correlate to the duration of oral bisphosphonate use and could indicate a recovery of bone remodeling with increased values if the oral bisphosphonate was discontinued. Diphosphonates 221-235 cytochrome P450 family 27 subfamily A member 1 Homo sapiens 50-53 18161132-0 2007 [Effectiveness of bisphosphonate administration for prevention of osteopenia during Gn-RH agonist therapy of endometriosis]. Diphosphonates 18-32 gonadotropin releasing hormone 1 Homo sapiens 84-89 18056045-5 2007 The inhibitory effects of the nitrogen-containing BPs (including alendronate, risedronate, ibandronate, and zoledronate) on osteoclasts appear to result from their inhibition of farnesyl pyrophosphate synthase (FPPS), a key branch-point enzyme in the mevalonate pathway. Diphosphonates 50-53 farnesyl diphosphate synthase Homo sapiens 178-209 18056045-5 2007 The inhibitory effects of the nitrogen-containing BPs (including alendronate, risedronate, ibandronate, and zoledronate) on osteoclasts appear to result from their inhibition of farnesyl pyrophosphate synthase (FPPS), a key branch-point enzyme in the mevalonate pathway. Diphosphonates 50-53 farnesyl diphosphate synthase Homo sapiens 211-215 17959891-1 2007 Nitrogen-containing bisphosphonates (nBPs) are bone-specific agents that inhibit farnesyl diphosphate synthase. Diphosphonates 20-35 farnesyl diphosphate synthase Homo sapiens 81-110 17914587-0 2007 Isoprenoid-independent pathway is involved in apoptosis induced by risedronate, a bisphosphonate, in which Bim plays a critical role in breast cancer cell line MCF-7. Diphosphonates 82-96 BCL2 like 11 Homo sapiens 107-110 18751789-4 2007 Interestingly, in patients with osteoporosis, combination therapy with bisphosphonates and PTH (1-34) is not synergistic in increasing bone density; bisphosphonates appear to blunt the effect of PTH (1-34). Diphosphonates 149-164 parathyroid hormone Homo sapiens 195-198 17845332-0 2007 Aromatase inhibitor-induced bone mineral loss and its prevention by bisphosphonate administration in postmenopausal breast cancer patients. Diphosphonates 68-82 cytochrome P450 family 19 subfamily A member 1 Homo sapiens 0-9 17845332-1 2007 AIM: To investigate aromatase inhibitor-induced bone mineral loss and its prevention by bisphosphonate administration in postmenopausal breast cancer patients. Diphosphonates 88-102 cytochrome P450 family 19 subfamily A member 1 Homo sapiens 20-29 17640631-0 2007 Inhibition of the mevalonate pathway and activation of p38 MAP kinase are independently regulated by nitrogen-containing bisphosphonates in breast cancer cells. Diphosphonates 121-136 mitogen-activated protein kinase 14 Homo sapiens 55-58 17640631-4 2007 We have shown that bisphosphonates also induce p38 activation, which signals resistance against the drug-induced growth inhibition through an unknown mechanism. Diphosphonates 19-34 mitogen-activated protein kinase 14 Homo sapiens 47-50 17640631-6 2007 Furthermore, p38 inhibitor augments bisphosphonate-induced growth inhibition by inducing an additional G2-phase cell cycle arrest. Diphosphonates 36-50 mitogen-activated protein kinase 14 Homo sapiens 13-16 17640631-7 2007 We also show that the nitrogen-containing bisphosphonate-induced effects on p38 phosphorylation occur before accumulation of unprenylated Rap1A or Rac1 activation. Diphosphonates 42-56 mitogen-activated protein kinase 14 Homo sapiens 76-79 17640631-7 2007 We also show that the nitrogen-containing bisphosphonate-induced effects on p38 phosphorylation occur before accumulation of unprenylated Rap1A or Rac1 activation. Diphosphonates 42-56 RAP1A, member of RAS oncogene family Homo sapiens 138-143 17640631-7 2007 We also show that the nitrogen-containing bisphosphonate-induced effects on p38 phosphorylation occur before accumulation of unprenylated Rap1A or Rac1 activation. Diphosphonates 42-56 Rac family small GTPase 1 Homo sapiens 147-151 17640631-12 2007 The bisphosphonate-induced p38 activation signals for resistance against these drugs, by promoting progression through the G2/M-checkpoint. Diphosphonates 4-18 mitogen-activated protein kinase 14 Homo sapiens 27-30 18751789-1 2007 The bisphosphonate class of antiresorptive drugs and active forms of parathyroid hormone (PTH (1-34)) have been used clinically to enhance bone mass and density in patients with osteoporosis. Diphosphonates 4-18 parathyroid hormone Homo sapiens 69-88 18751789-1 2007 The bisphosphonate class of antiresorptive drugs and active forms of parathyroid hormone (PTH (1-34)) have been used clinically to enhance bone mass and density in patients with osteoporosis. Diphosphonates 4-18 parathyroid hormone Homo sapiens 90-93 17379647-1 2007 Previous studies have indicated that bisphosphonate pretreatment can inhibit the anabolic actions of PTH. Diphosphonates 37-51 parathyroid hormone Mus musculus 101-104 17442659-7 2007 Bone ALP, PINP and OC decreased by 26%-47% compared with baseline with both bisphosphonates. Diphosphonates 76-91 alkaline phosphatase, placental Homo sapiens 5-8 17535895-2 2007 Here, we show that some bisphosphonates can also inhibit geranylgeranyl diphosphate synthase (GGPPS), as well as undecaprenyl diphosphate synthase (UPPS), a cis-prenyltransferase of interest as a target for antibacterial therapy. Diphosphonates 24-39 geranylgeranyl diphosphate synthase 1 Homo sapiens 57-92 17535895-2 2007 Here, we show that some bisphosphonates can also inhibit geranylgeranyl diphosphate synthase (GGPPS), as well as undecaprenyl diphosphate synthase (UPPS), a cis-prenyltransferase of interest as a target for antibacterial therapy. Diphosphonates 24-39 geranylgeranyl diphosphate synthase 1 Homo sapiens 94-99 17535895-3 2007 Our results on GGPPS (10 structures) show that there are three bisphosphonate-binding sites, consisting of FPP or isopentenyl diphosphate substrate-binding sites together with a GGPP product- or inhibitor-binding site. Diphosphonates 63-77 geranylgeranyl diphosphate synthase 1 Homo sapiens 15-20 17428243-11 2007 CONCLUSIONS: Bisphosphonate can prevent parathyroid hormone-related peptide (PTHrP)-mediated bone resorption when administered during the early phase of renal tumour growth, but has no effect on the tumour-induced development of hypercalcaemia, indicating a primary role for renal tubular reabsorption of calcium in the kidney by PTHrP in HHM. Diphosphonates 13-27 parathyroid hormone-like peptide Mus musculus 40-75 17428243-11 2007 CONCLUSIONS: Bisphosphonate can prevent parathyroid hormone-related peptide (PTHrP)-mediated bone resorption when administered during the early phase of renal tumour growth, but has no effect on the tumour-induced development of hypercalcaemia, indicating a primary role for renal tubular reabsorption of calcium in the kidney by PTHrP in HHM. Diphosphonates 13-27 parathyroid hormone-like peptide Mus musculus 77-82 17428243-11 2007 CONCLUSIONS: Bisphosphonate can prevent parathyroid hormone-related peptide (PTHrP)-mediated bone resorption when administered during the early phase of renal tumour growth, but has no effect on the tumour-induced development of hypercalcaemia, indicating a primary role for renal tubular reabsorption of calcium in the kidney by PTHrP in HHM. Diphosphonates 13-27 parathyroid hormone-like peptide Mus musculus 330-335 17535895-1 2007 Bisphosphonate drugs (e.g., Fosamax and Zometa) are thought to act primarily by inhibiting farnesyl diphosphate synthase (FPPS), resulting in decreased prenylation of small GTPases. Diphosphonates 0-14 farnesyl diphosphate synthase Homo sapiens 91-120 17535895-1 2007 Bisphosphonate drugs (e.g., Fosamax and Zometa) are thought to act primarily by inhibiting farnesyl diphosphate synthase (FPPS), resulting in decreased prenylation of small GTPases. Diphosphonates 0-14 farnesyl diphosphate synthase Homo sapiens 122-126 17214981-5 2007 Furthermore, excess pyrophosphate-resembling bisphosphonates prevent nitrogen-containing-bisphosphonate-induced accumulation of unprenylated Rap1A, p38 phosphorylation and growth inhibition in human MDA-MB-231 breast cancer and mouse AB-12 mesothelioma cells. Diphosphonates 45-60 RAP1A, member of RAS oncogene family Homo sapiens 141-146 17446718-8 2007 The role of hTERT is a new finding, which gives an alternative explanation for the direct effect of bisphosphonates on tumor cells. Diphosphonates 100-115 telomerase reverse transcriptase Homo sapiens 12-17 17374166-0 2007 The Interleukin-6 inflammation pathway from cholesterol to aging--role of statins, bisphosphonates and plant polyphenols in aging and age-related diseases. Diphosphonates 83-98 interleukin 6 Homo sapiens 4-17 17320499-6 2007 A preliminary analysis of the current biomedical literature in our research area using our tool suggests that S100A12, as well as a group of SMAD genes previously unstudied in relation to osteoporosis, may be highly relevant to the mechanism of action of bisphosphonates, that the function of osteocytes may be influenced by a family of important interleukins and interleukin-related molecules, and that the FYN oncogene may play an important role in regulating the apoptosis of bone cells in the context of degenerative bone diseases. Diphosphonates 255-270 S100 calcium binding protein A12 Homo sapiens 110-117 17320499-6 2007 A preliminary analysis of the current biomedical literature in our research area using our tool suggests that S100A12, as well as a group of SMAD genes previously unstudied in relation to osteoporosis, may be highly relevant to the mechanism of action of bisphosphonates, that the function of osteocytes may be influenced by a family of important interleukins and interleukin-related molecules, and that the FYN oncogene may play an important role in regulating the apoptosis of bone cells in the context of degenerative bone diseases. Diphosphonates 255-270 FYN proto-oncogene, Src family tyrosine kinase Homo sapiens 408-411 17192391-8 2007 However, OC-defective osteoprotegerin transgenic (OPG(Tg)) mice and bisphosphonate-treated mice were resistant to the effects of G-CSF administration upon bone tumor growth. Diphosphonates 68-82 colony stimulating factor 3 (granulocyte) Mus musculus 129-134 17214981-5 2007 Furthermore, excess pyrophosphate-resembling bisphosphonates prevent nitrogen-containing-bisphosphonate-induced accumulation of unprenylated Rap1A, p38 phosphorylation and growth inhibition in human MDA-MB-231 breast cancer and mouse AB-12 mesothelioma cells. Diphosphonates 45-60 mitogen-activated protein kinase 14 Homo sapiens 148-151 17214981-5 2007 Furthermore, excess pyrophosphate-resembling bisphosphonates prevent nitrogen-containing-bisphosphonate-induced accumulation of unprenylated Rap1A, p38 phosphorylation and growth inhibition in human MDA-MB-231 breast cancer and mouse AB-12 mesothelioma cells. Diphosphonates 45-59 RAP1A, member of RAS oncogene family Homo sapiens 141-146 17214981-5 2007 Furthermore, excess pyrophosphate-resembling bisphosphonates prevent nitrogen-containing-bisphosphonate-induced accumulation of unprenylated Rap1A, p38 phosphorylation and growth inhibition in human MDA-MB-231 breast cancer and mouse AB-12 mesothelioma cells. Diphosphonates 45-59 mitogen-activated protein kinase 14 Homo sapiens 148-151 17291279-5 2007 Vgamma2Vdelta2 T cells can also recognize high levels of IPP in certain tumors and in cells treated with pharmacological agents, such as bisphosphonates and alkylamines, that block farnesyl pyrophosphate synthase. Diphosphonates 137-152 farnesyl diphosphate synthase Homo sapiens 181-212 17343740-8 2007 PC3/OPN cells treated with bisphosphonate (BP) reproduce the down-regulation observed in PC3/OPN (RGA) and PC3/SiRNA cells. Diphosphonates 27-41 chromobox 8 Homo sapiens 0-3 17343740-8 2007 PC3/OPN cells treated with bisphosphonate (BP) reproduce the down-regulation observed in PC3/OPN (RGA) and PC3/SiRNA cells. Diphosphonates 27-41 secreted phosphoprotein 1 Homo sapiens 4-7 17343740-8 2007 PC3/OPN cells treated with bisphosphonate (BP) reproduce the down-regulation observed in PC3/OPN (RGA) and PC3/SiRNA cells. Diphosphonates 27-41 chromobox 8 Homo sapiens 89-92 17343740-8 2007 PC3/OPN cells treated with bisphosphonate (BP) reproduce the down-regulation observed in PC3/OPN (RGA) and PC3/SiRNA cells. Diphosphonates 27-41 secreted phosphoprotein 1 Homo sapiens 93-96 17343740-8 2007 PC3/OPN cells treated with bisphosphonate (BP) reproduce the down-regulation observed in PC3/OPN (RGA) and PC3/SiRNA cells. Diphosphonates 27-41 chromobox 8 Homo sapiens 89-92 17343740-8 2007 PC3/OPN cells treated with bisphosphonate (BP) reproduce the down-regulation observed in PC3/OPN (RGA) and PC3/SiRNA cells. Diphosphonates 43-45 chromobox 8 Homo sapiens 0-3 17343740-8 2007 PC3/OPN cells treated with bisphosphonate (BP) reproduce the down-regulation observed in PC3/OPN (RGA) and PC3/SiRNA cells. Diphosphonates 43-45 secreted phosphoprotein 1 Homo sapiens 4-7 17343740-8 2007 PC3/OPN cells treated with bisphosphonate (BP) reproduce the down-regulation observed in PC3/OPN (RGA) and PC3/SiRNA cells. Diphosphonates 43-45 chromobox 8 Homo sapiens 89-92 17343740-8 2007 PC3/OPN cells treated with bisphosphonate (BP) reproduce the down-regulation observed in PC3/OPN (RGA) and PC3/SiRNA cells. Diphosphonates 43-45 secreted phosphoprotein 1 Homo sapiens 93-96 17343740-8 2007 PC3/OPN cells treated with bisphosphonate (BP) reproduce the down-regulation observed in PC3/OPN (RGA) and PC3/SiRNA cells. Diphosphonates 43-45 chromobox 8 Homo sapiens 89-92 17208200-5 2007 Here, we show that this impairment results from potent and specific inhibition of geranylgeranyl pyrophosphate synthase, which leads to enhanced depletion of intracellular geranylgeranyl pyrophosphate relative to the nitrogenous bisphosphonate zoledronate. Diphosphonates 229-243 geranylgeranyl diphosphate synthase 1 Homo sapiens 82-119 16996129-2 2007 Newer nitrogen containing bisphosphonates such as zoledronate act, at least in part, by inhibiting farnesyl diphosphate synthase and subsequent protein prenylation, furthermore, limited data suggests that zoledronate exerts a direct anti-tumour effect against human myeloma cell lines. Diphosphonates 26-41 farnesyl diphosphate synthase Homo sapiens 99-128 17090032-3 2006 Here, we report the results of a solid-state (13)C, (15)N, and (31)P magic-angle sample spinning (MAS) NMR and quantum chemical investigation of several bisphosphonates, both as pure compounds and when bound to FPPS, to provide information about side-chain and phosphonate backbone protonation states when bound to the enzyme. Diphosphonates 153-168 farnesyl diphosphate synthase Homo sapiens 211-215 17277961-15 2007 The more active nitrogen containing bisphosphonates inhibit mevalonate metabolism due to the specific inhibition of farnesyl pyrophosphate synthase. Diphosphonates 36-51 farnesyl diphosphate synthase Homo sapiens 116-147 22460750-3 2007 For nitrogen-containing bisphosphonates there is a correlation between in vitro potency of inhibition of a specific enzyme, farnesyl pyrophosphate synthase, and their antiresorptive potency in vivo. Diphosphonates 24-39 farnesyl diphosphate synthase Homo sapiens 124-155 17090032-4 2006 We then used computational docking methods (with the charges assigned by NMR) to predict how several bisphosphonates bind to FPPS. Diphosphonates 101-116 farnesyl diphosphate synthase Homo sapiens 125-129 17062705-5 2006 RESULTS: Nitrogen-containing bisphosphonates act intracellularly by inhibiting farnesyl diphosphate synthase, an enzyme of the mevalonate pathway, thereby preventing prenylation of small GTPase signaling proteins required for normal cellular function. Diphosphonates 29-44 farnesyl diphosphate synthase Homo sapiens 79-108 17062705-6 2006 Inhibition of farnesyl diphosphate synthase also seems to account for their antitumor effects observed in vitro and for the activation of gamma,delta T cells, a feature of the acute-phase response to bisphosphonate treatment in humans. Diphosphonates 200-214 farnesyl diphosphate synthase Homo sapiens 14-43 17062721-5 2006 In randomized controlled trials, bisphosphonates (pamidronate and zoledronic acid) and selective estrogen receptor modulators (raloxifene and toremifene) increased bone mineral density in GnRH agonist-treated men. Diphosphonates 33-48 gonadotropin releasing hormone 1 Homo sapiens 188-192 16697713-0 2006 Bisphosphonates activate nucleotide receptors signaling and induce the expression of Hsp90 in osteoblast-like cell lines. Diphosphonates 0-15 heat shock protein 90 alpha family class A member 1 Homo sapiens 85-90 16697713-8 2006 In fact, functional inactivation of Hsp90 by the specific inhibitor 17-AAG prevents the bisphosphonate-induced mitogenic effects in osteoblasts. Diphosphonates 88-102 heat shock protein 90 alpha family class A member 1 Homo sapiens 36-41 16697713-9 2006 These findings show that bisphosphonates, by inducing ATP release, may also act through nucleotide receptors signaling leading to ERKs activation and may exert their mitogenic role on osteoblasts through the involvement of Hsp90. Diphosphonates 25-40 heat shock protein 90 alpha family class A member 1 Homo sapiens 223-228 16861125-4 2006 Treatment with bone-directed therapies, including intravenous bisphosphonates, radio-nuclides, and endothelin-1 antagonists, can provide palliative and therapeutic benefits for patients who have established bone metastases, and treatment with intravenous bisphosphonates may prevent the development of bone metastases. Diphosphonates 255-270 endothelin 1 Homo sapiens 99-111 16956297-3 2006 Bisphosphonates, pyrophosphate analogues in which the oxygen bridge between the two phosphorus atoms has been replaced by a carbon substituted with different side chains, are able to inhibit the FPPS enzyme. Diphosphonates 0-15 farnesyl diphosphate synthase Homo sapiens 195-199 16956297-4 2006 Moreover, nitrogen-containing bisphosphonates have been proposed as carbocation transition state analogues of FPPS. Diphosphonates 30-45 farnesyl diphosphate synthase Homo sapiens 110-114 16524968-0 2006 Could the long-term persistence of low serum calcium levels and high serum parathyroid hormone levels during bisphosphonate treatment predispose metastatic breast cancer patients to undergo osteonecrosis of the jaw? Diphosphonates 109-123 parathyroid hormone Homo sapiens 75-94 16957935-0 2006 Increased numbers of osteoclasts expressing cysteine proteinase cathepsin K in patients with infected osteoradionecrosis and bisphosphonate-associated osteonecrosis--a paradoxical observation? Diphosphonates 125-139 cathepsin K Homo sapiens 64-75 18751825-19 2006 Certain tap and bottled waters present with concentrations of calcium sufficient to exhibit a deleterious effect on bisphosphonate treatment. Diphosphonates 116-130 nuclear RNA export factor 1 Homo sapiens 8-11 16770552-3 2006 In the present study, we compared the effect of pamidronate and clodronate, two structurally different bisphosphonates, on the induction of TNF-alpha release by alumina ceramic (Al(2)O(3)) and ultra-high-molecular-weight-polyethylene (UHMWPE) particles. Diphosphonates 103-118 tumor necrosis factor Mus musculus 140-149 16544308-1 2006 The efficacy of hydroxyapatite (HAp) as a carrier was investigated to establish a method of local administration of bisphosphonates (Bps), which has currently been administered systemically. Diphosphonates 116-131 reticulon 3 Homo sapiens 32-35 16544308-4 2006 Different Bps-HAp composites were subsequently prepared and the concentration of Bps released from these composites was measured. Diphosphonates 10-13 reticulon 3 Homo sapiens 14-17 16544308-6 2006 The results revealed that (1) HAp solubility depends on the sintering temperature; (2) The concentration of released Bps could be controlled by regulating the sintering temperature of HAp as a carrier; and (3) Bps released from Bps-HAp composites reduced the number of osteoclasts. Diphosphonates 117-120 reticulon 3 Homo sapiens 30-33 16544308-6 2006 The results revealed that (1) HAp solubility depends on the sintering temperature; (2) The concentration of released Bps could be controlled by regulating the sintering temperature of HAp as a carrier; and (3) Bps released from Bps-HAp composites reduced the number of osteoclasts. Diphosphonates 117-120 reticulon 3 Homo sapiens 184-187 16544308-6 2006 The results revealed that (1) HAp solubility depends on the sintering temperature; (2) The concentration of released Bps could be controlled by regulating the sintering temperature of HAp as a carrier; and (3) Bps released from Bps-HAp composites reduced the number of osteoclasts. Diphosphonates 117-120 reticulon 3 Homo sapiens 184-187 16544308-6 2006 The results revealed that (1) HAp solubility depends on the sintering temperature; (2) The concentration of released Bps could be controlled by regulating the sintering temperature of HAp as a carrier; and (3) Bps released from Bps-HAp composites reduced the number of osteoclasts. Diphosphonates 210-213 reticulon 3 Homo sapiens 30-33 16544308-6 2006 The results revealed that (1) HAp solubility depends on the sintering temperature; (2) The concentration of released Bps could be controlled by regulating the sintering temperature of HAp as a carrier; and (3) Bps released from Bps-HAp composites reduced the number of osteoclasts. Diphosphonates 210-213 reticulon 3 Homo sapiens 184-187 16544308-6 2006 The results revealed that (1) HAp solubility depends on the sintering temperature; (2) The concentration of released Bps could be controlled by regulating the sintering temperature of HAp as a carrier; and (3) Bps released from Bps-HAp composites reduced the number of osteoclasts. Diphosphonates 210-213 reticulon 3 Homo sapiens 184-187 16544308-6 2006 The results revealed that (1) HAp solubility depends on the sintering temperature; (2) The concentration of released Bps could be controlled by regulating the sintering temperature of HAp as a carrier; and (3) Bps released from Bps-HAp composites reduced the number of osteoclasts. Diphosphonates 210-213 reticulon 3 Homo sapiens 30-33 16544308-6 2006 The results revealed that (1) HAp solubility depends on the sintering temperature; (2) The concentration of released Bps could be controlled by regulating the sintering temperature of HAp as a carrier; and (3) Bps released from Bps-HAp composites reduced the number of osteoclasts. Diphosphonates 210-213 reticulon 3 Homo sapiens 184-187 16544308-6 2006 The results revealed that (1) HAp solubility depends on the sintering temperature; (2) The concentration of released Bps could be controlled by regulating the sintering temperature of HAp as a carrier; and (3) Bps released from Bps-HAp composites reduced the number of osteoclasts. Diphosphonates 210-213 reticulon 3 Homo sapiens 184-187 16544308-7 2006 These findings indicated that Bps-HAp composites could be locally administered as a drug delivery system to areas with bone resorption. Diphosphonates 30-33 reticulon 3 Homo sapiens 34-37 16886623-4 2006 RESULTS: Incadronate, a third-generation bisphosphonate, was found to inhibit the caveolin-1 mRNA and protein expression in PC-3 prostate cells. Diphosphonates 41-55 caveolin 1 Homo sapiens 82-92 16798918-9 2006 CONCLUSIONS: 99Tc(m)-MDP three-phase bone scans who could be used as a screening test to detect subclinical osteonecrosis in patients who have received bisphosphonates. Diphosphonates 152-167 dipeptidase 1 Homo sapiens 21-24 16257277-0 2006 -511 C/T IL1B gene polymorphism is associated to resistance to bisphosphonates treatment in Paget disease of bone. Diphosphonates 63-78 interleukin 1 beta Homo sapiens 9-13 16019130-3 2006 Since aminopeptidase N (AP-N) is known to be involved in the metastasis of prostate cancer, we investigated the effect of bisphosphonate on AP-N expression. Diphosphonates 122-136 alanyl aminopeptidase, membrane Homo sapiens 140-144 16019130-5 2006 The inhibitory effect of AP-N mRNA expression was also observed in the cells treated with pravastatin and other nitrogen-containing bisphosphonates, which inhibit the key enzyme in the isoprenoid biosynthesis pathway. Diphosphonates 132-147 alanyl aminopeptidase, membrane Homo sapiens 25-29 16019130-9 2006 These above results indicate that the decrease in AP-N expression elicited by bisphosphonate is related to the inhibition of the mevalonate pathway. Diphosphonates 78-92 alanyl aminopeptidase, membrane Homo sapiens 50-54 16684881-2 2006 Because of their bone-selective pharmacokinetics, nitrogen-containing bisphosphonates (N-BPs), currently used as clinical inhibitors of bone-resorption diseases, target osteoclast farnesyl pyrophosphate synthase (FPPS) and inhibit protein prenylation. Diphosphonates 70-85 farnesyl diphosphate synthase Homo sapiens 180-211 16684881-2 2006 Because of their bone-selective pharmacokinetics, nitrogen-containing bisphosphonates (N-BPs), currently used as clinical inhibitors of bone-resorption diseases, target osteoclast farnesyl pyrophosphate synthase (FPPS) and inhibit protein prenylation. Diphosphonates 70-85 farnesyl diphosphate synthase Homo sapiens 213-217 16319976-4 2006 Bone-specific biochemical markers, notably type I collagen telopeptide cross-link by-products such as N-telopeptide (NTx) and C-telopeptide (CTx), have been shown to be effective tools for assessing the severity and extent of bone metastases, and the response to bisphosphonates. Diphosphonates 263-278 cytochrome P450 family 27 subfamily A member 1 Homo sapiens 141-144 16831938-10 2006 The key target for bisphosphonates is farnesyl pyrophosphate synthase (FPPS) within osteoclasts, and the recently elucidated crystal structure of this enzyme reveals how BPs bind to and inhibit at the active site via their critical N atoms. Diphosphonates 19-34 farnesyl diphosphate synthase Homo sapiens 38-69 16831938-10 2006 The key target for bisphosphonates is farnesyl pyrophosphate synthase (FPPS) within osteoclasts, and the recently elucidated crystal structure of this enzyme reveals how BPs bind to and inhibit at the active site via their critical N atoms. Diphosphonates 19-34 farnesyl diphosphate synthase Homo sapiens 71-75 16831938-10 2006 The key target for bisphosphonates is farnesyl pyrophosphate synthase (FPPS) within osteoclasts, and the recently elucidated crystal structure of this enzyme reveals how BPs bind to and inhibit at the active site via their critical N atoms. Diphosphonates 170-173 farnesyl diphosphate synthase Homo sapiens 38-69 16831938-10 2006 The key target for bisphosphonates is farnesyl pyrophosphate synthase (FPPS) within osteoclasts, and the recently elucidated crystal structure of this enzyme reveals how BPs bind to and inhibit at the active site via their critical N atoms. Diphosphonates 170-173 farnesyl diphosphate synthase Homo sapiens 71-75 16650801-2 2006 Although several years ago the molecular target of the potent nitrogen-containing BPs (N-BPs) was identified as farnesyl diphosphate synthase, an enzyme in the mevalonate pathway, recent data have shed new light on the precise mechanism of inhibition and demonstrated that the acute-phase reaction, an adverse effect of N-BPs, is also caused by inhibition of this enzyme. Diphosphonates 82-85 farnesyl diphosphate synthase Homo sapiens 112-141 16675582-6 2006 Both bisphosphonates also induced the phosphorylation of the p38 mitogen-activated protein kinase in AB12 and AC29 cells. Diphosphonates 5-20 mitogen-activated protein kinase 14 Mus musculus 61-64 16675582-7 2006 The inhibition of p38 augmented bisphosphonate-induced growth inhibition in these cells. Diphosphonates 32-46 mitogen-activated protein kinase 14 Mus musculus 18-21 16675582-8 2006 Bisphosphonate-induced p38 phosphorylation was not reversible by geranylgeraniol. Diphosphonates 0-14 mitogen-activated protein kinase 14 Mus musculus 23-26 16734383-0 2006 Inhibition of protein prenylation by bisphosphonates causes sustained activation of Rac, Cdc42, and Rho GTPases. Diphosphonates 37-52 thymoma viral proto-oncogene 1 Mus musculus 84-87 16734383-0 2006 Inhibition of protein prenylation by bisphosphonates causes sustained activation of Rac, Cdc42, and Rho GTPases. Diphosphonates 37-52 cell division cycle 42 Mus musculus 89-94 16734383-4 2006 INTRODUCTION: Nitrogen-containing bisphosphonates (N-BPs) are potent inhibitors of bone resorption that act by inhibiting farnesyl diphosphate synthase, thereby indirectly preventing the prenylation of Rho family GTPases that are required for the function and survival of bone-resorbing osteoclasts. Diphosphonates 34-49 farnesyl diphosphate synthetase Mus musculus 122-151 16501031-5 2006 Both EGTA and clodronate also prevented the bisphosphonate-induced inhibition of Rap1A prenylation, an effect that was reversed by addition of Ca2+. Diphosphonates 44-58 RAS-related protein 1a Mus musculus 81-86 16257150-5 2006 It seems that bisphosphonates can blunt the anabolic effect of parathyroid hormone (PTH) when given simultaneously. Diphosphonates 14-29 parathyroid hormone Homo sapiens 63-82 16257277-9 2006 CONCLUSIONS: Our results suggest that the -511 CC genotype of the IL1B gene could be related to resistance to bisphosphonates in patients with PDB. Diphosphonates 110-125 interleukin 1 beta Homo sapiens 66-70 16518076-3 2006 The studies showed that BPs inhibit lipopolysaccharide- or parathyroid hormone-induced osteoclast differentiation, fusion, attachment, actin ring formation, and activation and that both beta3 integrin and osteopontin have an important role in cytoskeletal rearrangements associated with cell attachment and resorption in osteoclasts. Diphosphonates 24-27 secreted phosphoprotein 1 Homo sapiens 205-216 16585363-6 2006 Early findings indicate that bisphosphonates upregulate bone morphogenetic protein-2 production and stimulate new bone formation. Diphosphonates 29-44 bone morphogenetic protein 2 Homo sapiens 56-84 16673205-2 2006 In addition, we demonstrated that incadronate amplified, and tiludronate suppressed PGF2alpha-induced VEGF synthesis among bisphosphonates, while alendronate or etidronate had no effect. Diphosphonates 123-138 vascular endothelial growth factor A Mus musculus 102-106 16932286-2 2006 When embedded in bone matrix, bisphosphonates are taken up by osteoclasts engaged in bone resorption, leading--mainly by inhibition of farnesyl diphosphate synthase, a key enzyme of the mevalonate pathway--to osteoclast apoptosis. Diphosphonates 30-45 farnesyl diphosphate synthase Homo sapiens 135-164 16730272-5 2006 Furthermore, the potent bisphosphonate zoledronic acid has been shown to be efficacious in reducing bone loss in premenopausal women receiving combination adjuvant hormone therapy (goserelin, a gonadotropin-releasing hormone agonist, plus either an AI or tamoxifen). Diphosphonates 24-38 gonadotropin releasing hormone 1 Homo sapiens 194-224 16515701-0 2006 The effect of bisphosphonates on gene expression: GAPDH as a housekeeping or a new target gene? Diphosphonates 14-29 glyceraldehyde-3-phosphate dehydrogenase Homo sapiens 50-55 16515701-6 2006 METHODS: We evaluated GAPDH gene expression by real time RT PCR in breast (MCF-7 and T47D) and prostate (PC3 and DU-145) cancer cell lines treated with amino and non-amino bisphosphonates. Diphosphonates 172-187 glyceraldehyde-3-phosphate dehydrogenase Homo sapiens 22-27 16489006-6 2006 Consistent with this notion, inhibition of bone resorption by the bisphosphonate ibandronate reduced COX-2 expression in MDA-MB-231 cells in bone. Diphosphonates 66-80 prostaglandin-endoperoxide synthase 2 Homo sapiens 101-106 16444581-0 2006 Inhibition of adenosine kinase by phosphonate and bisphosphonate derivatives. Diphosphonates 50-64 adenosine kinase Homo sapiens 14-30 16892359-1 2006 To understand the structural basis for bisphosphonate therapy of bone diseases, we solved the crystal structures of human farnesyl pyrophosphate synthase (FPPS) in its unliganded state, in complex with the nitrogen-containing bisphosphonate (N-BP) drugs zoledronate, pamidronate, alendronate, and ibandronate, and in the ternary complex with zoledronate and the substrate isopentenyl pyrophosphate (IPP). Diphosphonates 39-53 farnesyl diphosphate synthase Homo sapiens 122-153 16892359-1 2006 To understand the structural basis for bisphosphonate therapy of bone diseases, we solved the crystal structures of human farnesyl pyrophosphate synthase (FPPS) in its unliganded state, in complex with the nitrogen-containing bisphosphonate (N-BP) drugs zoledronate, pamidronate, alendronate, and ibandronate, and in the ternary complex with zoledronate and the substrate isopentenyl pyrophosphate (IPP). Diphosphonates 39-53 farnesyl diphosphate synthase Homo sapiens 155-159 16892359-1 2006 To understand the structural basis for bisphosphonate therapy of bone diseases, we solved the crystal structures of human farnesyl pyrophosphate synthase (FPPS) in its unliganded state, in complex with the nitrogen-containing bisphosphonate (N-BP) drugs zoledronate, pamidronate, alendronate, and ibandronate, and in the ternary complex with zoledronate and the substrate isopentenyl pyrophosphate (IPP). Diphosphonates 226-240 farnesyl diphosphate synthase Homo sapiens 122-153 16892359-1 2006 To understand the structural basis for bisphosphonate therapy of bone diseases, we solved the crystal structures of human farnesyl pyrophosphate synthase (FPPS) in its unliganded state, in complex with the nitrogen-containing bisphosphonate (N-BP) drugs zoledronate, pamidronate, alendronate, and ibandronate, and in the ternary complex with zoledronate and the substrate isopentenyl pyrophosphate (IPP). Diphosphonates 226-240 farnesyl diphosphate synthase Homo sapiens 155-159 16444581-6 2006 In contrast, a number of phosphonate and bisphosphonate derivatives, which included clodronate and etidronate, were found to inhibit the activity of purified AK in the presence of Pi. Diphosphonates 41-55 adenosine kinase Homo sapiens 158-160 16444581-10 2006 These results indicate that the enzyme AK provides an additional cellular target for the clinically widely used bisphosphonates and related compounds, which could possibly be exploited for a new therapeutic application. Diphosphonates 112-127 adenosine kinase Homo sapiens 39-41 16371477-10 2006 In a separate study with a model therapeutic vector, Ad-inducible nitric oxide synthase (iNOS) attached to the bisphosphonate-treated metal stent surface via D1, significant inhibition of restenosis was demonstrated (neointimal/media ratio 1.68 +/- 0.27 and 3.4 +/- 0.35; Ad-iNOS vs. control, P < 0.01). Diphosphonates 111-125 nitric oxide synthase 2 Rattus norvegicus 53-87 16371477-10 2006 In a separate study with a model therapeutic vector, Ad-inducible nitric oxide synthase (iNOS) attached to the bisphosphonate-treated metal stent surface via D1, significant inhibition of restenosis was demonstrated (neointimal/media ratio 1.68 +/- 0.27 and 3.4 +/- 0.35; Ad-iNOS vs. control, P < 0.01). Diphosphonates 111-125 nitric oxide synthase 2 Rattus norvegicus 89-93 16371477-10 2006 In a separate study with a model therapeutic vector, Ad-inducible nitric oxide synthase (iNOS) attached to the bisphosphonate-treated metal stent surface via D1, significant inhibition of restenosis was demonstrated (neointimal/media ratio 1.68 +/- 0.27 and 3.4 +/- 0.35; Ad-iNOS vs. control, P < 0.01). Diphosphonates 111-125 nitric oxide synthase 2 Rattus norvegicus 275-279 16216433-4 2006 Recently, farnesyl pyrophosphate synthase has been shown as a molecular target of nitrogen-containing bisphosphonates, and inhibition of post-translational prenylation of small molecular weight G proteins is likely involved in their anti-resorptive activity on osteoclasts. Diphosphonates 102-117 farnesyl diphosphate synthase Homo sapiens 10-41 16506358-9 2006 In postmenopausal osteoporotic women, both oral and intravenous bisphosphonate treatment resulted in a significant reduction in serum cathepsin K levels (p = 0.03) with most of the effect occurring after one month (mean% change: -33%). Diphosphonates 64-78 cathepsin K Homo sapiens 134-145 16506358-10 2006 In patients with mild Paget"s disease, serum cathepsin K levels decreased during bisphosphonate treatment. Diphosphonates 81-95 cathepsin K Homo sapiens 45-56 16698685-8 2006 DISCUSSION: The present study has demonstrated that type I IFN could enhance the anti-leukemic cytotoxicity of expanded gammadelta T cells, which implies that in vitro bisphosphonate (such as zoledronate)-expanded and type I IFN-activated gammadelta T cells could be applied to immunotherapy for hematologic malignancies such as leukemia and lymphoma. Diphosphonates 168-182 interferon alpha 1 Homo sapiens 59-62 16698685-8 2006 DISCUSSION: The present study has demonstrated that type I IFN could enhance the anti-leukemic cytotoxicity of expanded gammadelta T cells, which implies that in vitro bisphosphonate (such as zoledronate)-expanded and type I IFN-activated gammadelta T cells could be applied to immunotherapy for hematologic malignancies such as leukemia and lymphoma. Diphosphonates 168-182 interferon alpha 1 Homo sapiens 225-228 16862397-7 2006 In multivariate analyses, risk of adherence failure was higher for calcitonin (hazard ratio=2.7 vs weekly bisphosphonate therapy, p<0.01), but comparable for all other therapies. Diphosphonates 106-120 calcitonin related polypeptide alpha Homo sapiens 67-77 16435076-0 2006 Changes in the RANK ligand/osteoprotegerin system are correlated to changes in bone mineral density in bisphosphonate-treated osteoporotic patients. Diphosphonates 103-117 TNF receptor superfamily member 11b Homo sapiens 27-42 16435076-1 2006 INTRODUCTION: Since the soluble receptor activator of the NF-kappaB ligand (sRANKL) as well as the endogenous anti-resorptive cytokine osteoprotegerin (OPG) are produced by osteoblasts and given that these cells undergo significant changes during antiresorptive treatment, we hypothesized that treatment with bisphosphonates (BP) would be accompanied by changes in serum OPG and sRANKL levels. Diphosphonates 309-324 TNF receptor superfamily member 11b Homo sapiens 135-150 16087705-4 2005 In the combined presence of LPS and BP, bone-resorbing osteoclasts were smaller and the sealing zone diffuse, reflecting reduced actin, OPN, and beta3 integrin staining. Diphosphonates 36-38 secreted phosphoprotein 1 Mus musculus 136-139 16435076-1 2006 INTRODUCTION: Since the soluble receptor activator of the NF-kappaB ligand (sRANKL) as well as the endogenous anti-resorptive cytokine osteoprotegerin (OPG) are produced by osteoblasts and given that these cells undergo significant changes during antiresorptive treatment, we hypothesized that treatment with bisphosphonates (BP) would be accompanied by changes in serum OPG and sRANKL levels. Diphosphonates 326-328 TNF receptor superfamily member 11b Homo sapiens 135-150 16435076-11 2006 Univariate regression analysis demonstrated that changes in serum OPG levels after 12 months of BP treatment were positively and better correlated to BMD changes (trochanter: r=0.59, p<0.0001; neck: r=0.50, p<0.001) than those of sCTX, which showed the expected negative correlation to BMD change (trochanter: r=-0.35, p=0.03; neck: r=-0.23, p=0.16). Diphosphonates 96-98 TNF receptor superfamily member 11b Homo sapiens 66-69 16435076-15 2006 CONCLUSIONS: We conclude that with BP treatment, changes in serum OPG levels, unlike changes in sCTX levels, are positively correlated to changes in BMD response. Diphosphonates 35-37 TNF receptor superfamily member 11b Homo sapiens 66-69 16435076-16 2006 The BP-related changes in serum OPG levels during treatment could result from effects on osteoclastogenesis and osteoclast apoptosis as well as from a direct stimulatory effect on osteoblastic OPG production. Diphosphonates 4-6 TNF receptor superfamily member 11b Homo sapiens 32-35 16435076-16 2006 The BP-related changes in serum OPG levels during treatment could result from effects on osteoclastogenesis and osteoclast apoptosis as well as from a direct stimulatory effect on osteoblastic OPG production. Diphosphonates 4-6 TNF receptor superfamily member 11b Homo sapiens 193-196 16435076-17 2006 These changes in OPG levels may be used to predict the individual response of patients to BP treatment. Diphosphonates 90-92 TNF receptor superfamily member 11b Homo sapiens 17-20 21208538-4 2005 METHODS: The cytotoxic effect of bisphosphonates on lung cancer cells and human normal liver cells was determined by sulforhodamine B (SRB) assay. Diphosphonates 33-48 chaperonin containing TCP1 subunit 4 Homo sapiens 117-133 21208538-4 2005 METHODS: The cytotoxic effect of bisphosphonates on lung cancer cells and human normal liver cells was determined by sulforhodamine B (SRB) assay. Diphosphonates 33-48 chaperonin containing TCP1 subunit 4 Homo sapiens 135-138 16381543-1 2005 Bisphosphonates have shown significant clinical benefit in reducing skeletal fractures in patients with multiple myeloma or bone: penicillin VK 500 mg or amoxicillin 500 mg; both 4 times daily (QID) initially and twice daily (BID) for maintenance, If penicillin allergic: 1. Diphosphonates 0-15 BH3 interacting domain death agonist Homo sapiens 226-229 16320159-4 2005 We investigated a possible correlation between ET-1 plasma concentrations and bone metabolism in patients with PD and whether ET-1 plasma levels are regulated by i. v. bisphosphonate treatment. Diphosphonates 168-182 endothelin 1 Homo sapiens 126-130 16306104-0 2005 Serum tartrate-resistant acid phosphatase 5b or amino-terminal propeptide of type I procollagen for monitoring bisphosphonate therapy in postmenopausal osteoporosis? Diphosphonates 111-125 collagen type I alpha 2 chain Homo sapiens 77-95 16100524-3 2005 The aim of the present study was to determine the effect of alendronate, one of the nitrogen-containing bisphosphonates on the phoshoinositide 3-kinase (PI3K)-Akt-NFkappaB pathway, the major cell survival pathway. Diphosphonates 104-119 AKT serine/threonine kinase 1 Homo sapiens 159-162 16100524-3 2005 The aim of the present study was to determine the effect of alendronate, one of the nitrogen-containing bisphosphonates on the phoshoinositide 3-kinase (PI3K)-Akt-NFkappaB pathway, the major cell survival pathway. Diphosphonates 104-119 nuclear factor kappa B subunit 1 Homo sapiens 163-171 16167056-3 2005 Bisphosphonates, such as zoledronate, have been shown to inhibit the oncogenicity of Ras, an important downstream effector of Bcr-Abl. Diphosphonates 0-15 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 126-133 16274312-1 2005 BACKGROUND: The aim of the present study was to evaluate the effects of systemic administration of low-dose doxycycline and a bisphosphonate, alendronate, on serum levels of interleukin-1beta (IL-1beta), osteocalcin (OC), and C-reactive protein (CRP) in experimental periodontitis in rats. Diphosphonates 126-140 interleukin 1 beta Rattus norvegicus 174-191 16274312-1 2005 BACKGROUND: The aim of the present study was to evaluate the effects of systemic administration of low-dose doxycycline and a bisphosphonate, alendronate, on serum levels of interleukin-1beta (IL-1beta), osteocalcin (OC), and C-reactive protein (CRP) in experimental periodontitis in rats. Diphosphonates 126-140 interleukin 1 beta Rattus norvegicus 193-201 16193235-0 2005 Enhancement of crude bone morphogenetic protein-induced new bone formation and normalization of endochondral ossification by bisphosphonate treatment in osteoprotegerin-deficient mice. Diphosphonates 125-139 tumor necrosis factor receptor superfamily, member 11b (osteoprotegerin) Mus musculus 153-168 16393773-0 2005 The inhibitory effect of bisphosphonates on glucocorticoid-induced RANKL expression in human cells. Diphosphonates 25-40 TNF superfamily member 11 Homo sapiens 67-72 16393773-2 2005 However, little is known about the effect of bisphosphonates on glucocorticoid-induced RANKL expression in human cells. Diphosphonates 45-60 TNF superfamily member 11 Homo sapiens 87-92 16393773-3 2005 Our study was intended to clarify effects of bisphosphonates on glucocorticoid-induced RANKL expression in human cells. Diphosphonates 45-60 TNF superfamily member 11 Homo sapiens 87-92 16393773-11 2005 Bisphosphonates inhibited glucocorticoid-induced RANKL expression, suggesting that these effects might be a new therapeutic mechanism for bisphosphonates. Diphosphonates 0-15 TNF superfamily member 11 Homo sapiens 49-54 16393773-11 2005 Bisphosphonates inhibited glucocorticoid-induced RANKL expression, suggesting that these effects might be a new therapeutic mechanism for bisphosphonates. Diphosphonates 138-153 TNF superfamily member 11 Homo sapiens 49-54 16142752-10 2005 CONCLUSION: The reduced efficacy of bisphosphonates to stop bone erosion in the inflamed joints of RA patients may result from local high levels of TNF up-regulating Ets-2 expression in osteoclasts, which in turn stimulates Bcl-xL expression in them and reduces their susceptibility to bisphosphonate-induced apoptosis. Diphosphonates 36-51 BCL2 like 1 Homo sapiens 224-230 16037953-3 2005 To explore the feasibility of creating cleavable BP-protein conjugates, an amine- and a thiol-containing BP were conjugated to the model protein Bovine Serum Albumin (BSA) with N-succinimidyl-3-(2-pyridyldithio)propionate (SPDP), which resulted in disulfide-linked BP-BSA conjugates. Diphosphonates 49-51 albumin Homo sapiens 152-165 16037953-3 2005 To explore the feasibility of creating cleavable BP-protein conjugates, an amine- and a thiol-containing BP were conjugated to the model protein Bovine Serum Albumin (BSA) with N-succinimidyl-3-(2-pyridyldithio)propionate (SPDP), which resulted in disulfide-linked BP-BSA conjugates. Diphosphonates 105-107 albumin Homo sapiens 152-165 16037953-3 2005 To explore the feasibility of creating cleavable BP-protein conjugates, an amine- and a thiol-containing BP were conjugated to the model protein Bovine Serum Albumin (BSA) with N-succinimidyl-3-(2-pyridyldithio)propionate (SPDP), which resulted in disulfide-linked BP-BSA conjugates. Diphosphonates 105-107 albumin Homo sapiens 152-165 16142752-10 2005 CONCLUSION: The reduced efficacy of bisphosphonates to stop bone erosion in the inflamed joints of RA patients may result from local high levels of TNF up-regulating Ets-2 expression in osteoclasts, which in turn stimulates Bcl-xL expression in them and reduces their susceptibility to bisphosphonate-induced apoptosis. Diphosphonates 36-51 tumor necrosis factor Homo sapiens 148-151 16142752-10 2005 CONCLUSION: The reduced efficacy of bisphosphonates to stop bone erosion in the inflamed joints of RA patients may result from local high levels of TNF up-regulating Ets-2 expression in osteoclasts, which in turn stimulates Bcl-xL expression in them and reduces their susceptibility to bisphosphonate-induced apoptosis. Diphosphonates 36-51 ETS proto-oncogene 2, transcription factor Homo sapiens 166-171 16204052-0 2005 The bisphosphonate YM529 inhibits osteolytic and osteoblastic changes and CXCR-4-induced invasion in prostate cancer. Diphosphonates 4-18 chemokine (C-X-C motif) receptor 4 Mus musculus 74-80 16101188-2 2005 We hypothesized that bisphosphonate treatment and the subsequent fall in serum calcium might induce changes in the RANK/RANKL/OPG system, which plays a pivotal role in the regulation of bone resorption. Diphosphonates 21-35 TNF superfamily member 11 Homo sapiens 120-125 16101188-2 2005 We hypothesized that bisphosphonate treatment and the subsequent fall in serum calcium might induce changes in the RANK/RANKL/OPG system, which plays a pivotal role in the regulation of bone resorption. Diphosphonates 21-35 TNF receptor superfamily member 11b Homo sapiens 126-129 16142752-10 2005 CONCLUSION: The reduced efficacy of bisphosphonates to stop bone erosion in the inflamed joints of RA patients may result from local high levels of TNF up-regulating Ets-2 expression in osteoclasts, which in turn stimulates Bcl-xL expression in them and reduces their susceptibility to bisphosphonate-induced apoptosis. Diphosphonates 36-50 tumor necrosis factor Homo sapiens 148-151 16142752-10 2005 CONCLUSION: The reduced efficacy of bisphosphonates to stop bone erosion in the inflamed joints of RA patients may result from local high levels of TNF up-regulating Ets-2 expression in osteoclasts, which in turn stimulates Bcl-xL expression in them and reduces their susceptibility to bisphosphonate-induced apoptosis. Diphosphonates 36-50 ETS proto-oncogene 2, transcription factor Homo sapiens 166-171 16142752-10 2005 CONCLUSION: The reduced efficacy of bisphosphonates to stop bone erosion in the inflamed joints of RA patients may result from local high levels of TNF up-regulating Ets-2 expression in osteoclasts, which in turn stimulates Bcl-xL expression in them and reduces their susceptibility to bisphosphonate-induced apoptosis. Diphosphonates 36-50 BCL2 like 1 Homo sapiens 224-230 15845617-6 2005 In both models, OPG (0.2-5 mg/kg) caused rapid reversal of established hypercalcemia, and the speed and duration of hypercalcemia suppression were significantly greater with OPG (5 mg/kg) than with high-dose bisphosphonates (pamidronate or zoledronic acid, 5 mg/kg). Diphosphonates 208-223 tumor necrosis factor receptor superfamily, member 11b (osteoprotegerin) Mus musculus 16-19 16006204-1 2005 Nitrogen-containing bisphosphonate drugs such as risedronate act by inhibiting farnesyl diphosphate synthase, thereby disrupting protein prenylation in osteoclasts. Diphosphonates 20-34 farnesyl diphosphate synthetase Mus musculus 79-108 15978718-0 2005 Bisphosphonates decrease telomerase activity and hTERT expression in MCF-7 breast cancer cells. Diphosphonates 0-15 telomerase reverse transcriptase Homo sapiens 49-54 15921672-0 2005 Autoactivation profiles of calcium-dependent matrix metalloproteinase-2 and -9 in inflammatory synovial fluid: effect of pyrophosphate and bisphosphonates. Diphosphonates 139-154 matrix metallopeptidase 2 Homo sapiens 45-78 16034098-5 2005 administration of nitrogen-containing bisphosphonate or pyrophosphomonoester drugs into cynomolgus monkeys combined with s.c. low-dose (6 x 10(5) U/animal) IL-2 induces a large pool of CD27+ and CD27- effector/memory T cells in the peripheral blood of treated animals. Diphosphonates 38-52 CD27 antigen Macaca fascicularis 185-189 15802773-1 2005 Parathyroid hormone (PTH) is a promising bone formation-stimulating agent, and the recent large-scale randomized controlled trial (RCT) revealed that parathyroid hormone increases and reduces lumbar bone mineral density and fracture risk, respectively, more potently than bisphosphonates. Diphosphonates 272-287 parathyroid hormone Homo sapiens 0-19 15828834-1 2005 We report the design, synthesis and testing of a series of novel bisphosphonates, pyridinium-1-yl-hydroxy-bisphosphonates, based on the results of comparative molecular similarity indices analysis and pharmacophore modeling studies of farnesyl diphosphate synthase (FPPS) inhibition, human Vgamma2Vdelta2 T cell activation and bone resorption inhibition. Diphosphonates 65-80 farnesyl diphosphate synthase Homo sapiens 235-264 15828834-1 2005 We report the design, synthesis and testing of a series of novel bisphosphonates, pyridinium-1-yl-hydroxy-bisphosphonates, based on the results of comparative molecular similarity indices analysis and pharmacophore modeling studies of farnesyl diphosphate synthase (FPPS) inhibition, human Vgamma2Vdelta2 T cell activation and bone resorption inhibition. Diphosphonates 65-80 farnesyl diphosphate synthase Homo sapiens 266-270 15930357-2 2005 In this study, we examined the roles of parathyroid hormone-related protein (PTHrP) in the development of bisphosphonate- and calcitonin-refractory HHM. Diphosphonates 106-120 parathyroid hormone-like hormone Rattus norvegicus 40-75 15930357-2 2005 In this study, we examined the roles of parathyroid hormone-related protein (PTHrP) in the development of bisphosphonate- and calcitonin-refractory HHM. Diphosphonates 106-120 parathyroid hormone-like hormone Rattus norvegicus 77-82 15930357-11 2005 Thus, blockage of PTHrP functions by a neutralizing antibody against PTHrP would benefit patients who develop bisphosphonate- or calcitonin-refractory HHM. Diphosphonates 110-124 parathyroid hormone like hormone Homo sapiens 18-23 15930357-11 2005 Thus, blockage of PTHrP functions by a neutralizing antibody against PTHrP would benefit patients who develop bisphosphonate- or calcitonin-refractory HHM. Diphosphonates 110-124 parathyroid hormone like hormone Homo sapiens 69-74 15922088-1 2005 We have previously reported that prostaglandin F2alpha (PGF2alpha) activates p44/p42 mitogen-activated protein (MAP) kinase through protein kinase C (PKC), resulting in the synthesis of vascular endothelial growth factor (VEGF) in osteoblast-like MC3T3-E1 cells, and that incadronate, a bisphosphonate, amplifies the VEGF synthesis. Diphosphonates 287-301 mitogen-activated protein kinase 3 Mus musculus 77-80 15922088-1 2005 We have previously reported that prostaglandin F2alpha (PGF2alpha) activates p44/p42 mitogen-activated protein (MAP) kinase through protein kinase C (PKC), resulting in the synthesis of vascular endothelial growth factor (VEGF) in osteoblast-like MC3T3-E1 cells, and that incadronate, a bisphosphonate, amplifies the VEGF synthesis. Diphosphonates 287-301 cyclin-dependent kinase 20 Mus musculus 81-84 15922088-1 2005 We have previously reported that prostaglandin F2alpha (PGF2alpha) activates p44/p42 mitogen-activated protein (MAP) kinase through protein kinase C (PKC), resulting in the synthesis of vascular endothelial growth factor (VEGF) in osteoblast-like MC3T3-E1 cells, and that incadronate, a bisphosphonate, amplifies the VEGF synthesis. Diphosphonates 287-301 vascular endothelial growth factor A Mus musculus 186-220 15802773-1 2005 Parathyroid hormone (PTH) is a promising bone formation-stimulating agent, and the recent large-scale randomized controlled trial (RCT) revealed that parathyroid hormone increases and reduces lumbar bone mineral density and fracture risk, respectively, more potently than bisphosphonates. Diphosphonates 272-287 parathyroid hormone Homo sapiens 21-24 15590626-2 2005 However, whereas estrogens activate ERKs via an extranuclear function of the estrogen receptor, bisphosphonates do so by opening connexin 43 hemichannels. Diphosphonates 96-111 gap junction protein alpha 1 Homo sapiens 129-140 15694415-0 2005 Bisphosphonates induce inflammation and rupture of atherosclerotic plaques in apolipoprotein-E null mice. Diphosphonates 0-15 apolipoprotein E Mus musculus 78-94 15694415-11 2005 Our finding of plaque inflammation and rupture in bisphosphonate-treated Apo-E-/- mice may provide the first animal model for studies aimed at characterizing mechanisms of plaque rupture in animal models. Diphosphonates 50-64 apolipoprotein E Mus musculus 73-78 15670755-0 2005 Nitrogen-containing bisphosphonate, YM529/ONO-5920 (a novel minodronic acid), inhibits RANKL expression in a cultured bone marrow stromal cell line ST2. Diphosphonates 20-34 TNF superfamily member 11 Homo sapiens 87-92 15670755-0 2005 Nitrogen-containing bisphosphonate, YM529/ONO-5920 (a novel minodronic acid), inhibits RANKL expression in a cultured bone marrow stromal cell line ST2. Diphosphonates 20-34 ST2 Homo sapiens 148-151 15590626-6 2005 Instead, the effect of bisphosphonates is abolished when ERKs are restricted to the nucleus by blocking CRM1/exportin1-mediated nuclear protein export or by expressing nuclear-anchored ERKs, but it is unaffected in cells expressing cytoplasmic-anchored ERKs. Diphosphonates 23-38 exportin 1 Homo sapiens 104-108 15590626-6 2005 Instead, the effect of bisphosphonates is abolished when ERKs are restricted to the nucleus by blocking CRM1/exportin1-mediated nuclear protein export or by expressing nuclear-anchored ERKs, but it is unaffected in cells expressing cytoplasmic-anchored ERKs. Diphosphonates 23-38 exportin 1 Homo sapiens 109-118 15590626-7 2005 Connexin 43/ERK-mediated anti-apoptosis induced by bisphosphonates requires the kinase activity of the cytoplasmic target of ERKs, p90(RSK), which in turn phosphorylates the pro-apoptotic protein BAD and C/EBPbeta. Diphosphonates 51-66 gap junction protein alpha 1 Homo sapiens 0-11 15590626-7 2005 Connexin 43/ERK-mediated anti-apoptosis induced by bisphosphonates requires the kinase activity of the cytoplasmic target of ERKs, p90(RSK), which in turn phosphorylates the pro-apoptotic protein BAD and C/EBPbeta. Diphosphonates 51-66 mitogen-activated protein kinase 1 Homo sapiens 12-15 15590626-7 2005 Connexin 43/ERK-mediated anti-apoptosis induced by bisphosphonates requires the kinase activity of the cytoplasmic target of ERKs, p90(RSK), which in turn phosphorylates the pro-apoptotic protein BAD and C/EBPbeta. Diphosphonates 51-66 transferrin receptor Homo sapiens 131-134 15590626-7 2005 Connexin 43/ERK-mediated anti-apoptosis induced by bisphosphonates requires the kinase activity of the cytoplasmic target of ERKs, p90(RSK), which in turn phosphorylates the pro-apoptotic protein BAD and C/EBPbeta. Diphosphonates 51-66 ribosomal protein S6 kinase A2 Homo sapiens 135-138 15590626-7 2005 Connexin 43/ERK-mediated anti-apoptosis induced by bisphosphonates requires the kinase activity of the cytoplasmic target of ERKs, p90(RSK), which in turn phosphorylates the pro-apoptotic protein BAD and C/EBPbeta. Diphosphonates 51-66 CCAAT enhancer binding protein beta Homo sapiens 204-213 15659323-0 2005 Rat model of the hypercalcaemia induced by parathyroid hormone-related protein: characteristics of three bisphosphonates. Diphosphonates 105-120 parathyroid hormone-like hormone Rattus norvegicus 43-78 15701876-0 2005 A third-generation bisphosphonate, minodronic acid (YM529), augments the interferon alpha/beta-mediated inhibition of renal cell cancer cell growth both in vitro and in vivo. Diphosphonates 19-33 interferon alpha Mus musculus 73-89 15577056-3 2004 A recent investigation suggested that bisphosphonates might prevent arterial calcification through a mechanism associated with the enhanced production of parathyroid hormone-related peptide from vascular smooth muscle cells. Diphosphonates 38-53 parathyroid hormone like hormone Homo sapiens 154-189 15935563-5 2005 Anti-inflammatory properties of statins and bisphosphonates are due to isoprenoid depletion with subsequent inhibition of IL-6 mediated inflammation. Diphosphonates 44-59 interleukin 6 Homo sapiens 122-126 15935563-7 2005 Prevention of atherosclerotic vascular disease and age-related disorders will be by utilization of cholesterol lowering agents or techniques and/or treatment with statins and/or bisphosphonates to inhibit IL-6 inflammation through regulation of cholesterol metabolism. Diphosphonates 178-193 interleukin 6 Homo sapiens 205-209 15346059-8 2004 Annexin V staining, presence of active cleaved form of caspase-3, and disappearance of poly (ADP-ribose) polymerase on Western blotting indicated activation of apoptosis by bisphosphonates in giant cell tumor. Diphosphonates 173-188 poly(ADP-ribose) polymerase 1 Homo sapiens 87-115 15046901-8 2004 Bisphosphonates also enhanced gene expression of BMP-2, Type I collagen and osteocalcin. Diphosphonates 0-15 bone morphogenetic protein 2 Homo sapiens 49-54 15046901-8 2004 Bisphosphonates also enhanced gene expression of BMP-2, Type I collagen and osteocalcin. Diphosphonates 0-15 bone gamma-carboxyglutamate protein Homo sapiens 76-87 15037971-4 2004 We hypothesized that in bisphosphonates may induce apoptosis not only in osteoclast-like giant cells but also in neoplastic stromal cells of GCT both in vitro and in vivo. Diphosphonates 24-39 glutaminyl-peptide cyclotransferase Homo sapiens 141-144 15274277-3 2004 In this study, we tested the effects of calcitriol (1alpha,25-dihydroxy-vitamin-D3) and the bisphosphonate pamidronate on titanium-particle- and TNF-alpha-induced release of interleukin-6 and suppression of osteoblast-specific gene expressions in bone-marrow-derived stromal cells with an osteoblastic phenotype. Diphosphonates 92-106 tumor necrosis factor Homo sapiens 145-154 16440584-0 2005 Minodronate, a nitrogen-containing bisphosphonate, inhibits advanced glycation end product-induced vascular cell adhesion molecule-1 expression in endothelial cells by suppressing reactive oxygen species generation. Diphosphonates 35-49 vascular cell adhesion molecule 1 Homo sapiens 99-132 16440584-3 2005 We have previously shown that minodronate, a nitrogen-containing bisphosphonate, blocked the angiogenic signaling of vascular endothelial growth factor in ECs through its antioxidative properties. Diphosphonates 65-79 vascular endothelial growth factor A Homo sapiens 117-151 15324309-3 2004 We hypothesized that ZOL (zoledronic acid), a potent third-generation BP, may induce the expression of proteins associated with the bone-forming potential of osteoblastic cells such as BSP (bone sialo-protein). Diphosphonates 70-72 integrin binding sialoprotein Homo sapiens 185-188 15324309-3 2004 We hypothesized that ZOL (zoledronic acid), a potent third-generation BP, may induce the expression of proteins associated with the bone-forming potential of osteoblastic cells such as BSP (bone sialo-protein). Diphosphonates 70-72 integrin binding sialoprotein Homo sapiens 190-208 15522410-0 2004 Release of iron from transferrin by phosphonocarboxylate and diphosphonate chelating agents. Diphosphonates 61-74 transferrin Homo sapiens 21-32 15522410-1 2004 The rates at which phosphonocarboxylate and diphosphonate ligands remove iron from the serum iron transport protein transferrin at 25 degrees C and pH 7.4 have been evaluated. Diphosphonates 44-57 transferrin Homo sapiens 116-127 15230343-1 2004 Disodium clodronate (dichloromethylene bisphosphonic acid, disodium salt; CAS 22560-50-5) is a bisphosphonate that has demonstrated efficacy in patients with a variety of diseases of enhanced bone resorption. Diphosphonates 95-109 BCAR1 scaffold protein, Cas family member Homo sapiens 74-77 15203955-1 2004 In order to decrease the peri-implant bone loss during the life-time of the implant, oral use of anti-osteoporosis drugs (like bisphosphonates) has been suggested. Diphosphonates 127-142 perilipin 1 Homo sapiens 25-29 15089762-13 2004 After chemotherapy syndecan-1 and OPG levels were found to be decreased in responders and syndecan-1 level was reduced in patients receiving bisphosphonates alone. Diphosphonates 141-156 syndecan 1 Homo sapiens 90-100 14672944-3 2004 Here we present crystal structures of substrate and bisphosphonate complexes of FPPS. Diphosphonates 52-66 farnesyl diphosphate synthase Homo sapiens 80-84 15102578-1 2004 In osteoporosis, both the bisphosphonate alendronate and parathyroid hormone (1-34) (PTH (1-34) ) have been shown to reduce the incidence of fractures. Diphosphonates 26-40 parathyroid hormone Homo sapiens 85-88 15152817-0 2004 Inhibitory effect of a novel bisphosphonate, TRK-530, on dental calculus formation in rats. Diphosphonates 29-43 neurotrophic receptor tyrosine kinase 1 Rattus norvegicus 45-48 15152817-1 2004 BACKGROUND: A newly developed bisphosphonate, TRK-530 (disodium dihydrogen[4-(methylthio)phenylthio]methanebisphosphonate), has recently been reported to show anti-inflammatory and anti-bone-resorbing activity. Diphosphonates 30-44 neurotrophic receptor tyrosine kinase 1 Rattus norvegicus 46-49 14965371-0 2004 p53-independent anti-tumor effects of the nitrogen-containing bisphosphonate zoledronic acid. Diphosphonates 62-76 tumor protein p53 Homo sapiens 0-3 16036064-5 2003 For nitrogen-containing bisphosphonates, the direct intracellular target is the enzyme farnesyl diphosphate synthase in the cholesterol biosynthetic pathway. Diphosphonates 24-39 farnesyl diphosphate synthase Homo sapiens 87-116 14640924-7 2003 Monitoring of both BMD and BCM may indicate when to consider reinitiation of bisphosphonate therapy. Diphosphonates 77-91 TNF receptor superfamily member 17 Homo sapiens 27-30 14654555-9 2003 Bisphosphonates showed broad protective activity against tumor-driven osteolysis, Immunohistochemical evaluation of s.c. and intratibially implanted cells demonstrated the expression of PTHrP and TGF-beta1. Diphosphonates 0-15 parathyroid hormone-like hormone Rattus norvegicus 186-191 14654555-9 2003 Bisphosphonates showed broad protective activity against tumor-driven osteolysis, Immunohistochemical evaluation of s.c. and intratibially implanted cells demonstrated the expression of PTHrP and TGF-beta1. Diphosphonates 0-15 transforming growth factor, beta 1 Rattus norvegicus 196-205 13679234-0 2003 A new bisphosphonate, YM529 induces apoptosis in HL60 cells by decreasing phosphorylation of single survival signal ERK. Diphosphonates 6-20 mitogen-activated protein kinase 1 Homo sapiens 116-119 13679234-12 2003 These results suggest that YM529, the new bisphosphonate, induced apoptosis when inhibit GGPP synthase and consequently decreased the levels of phosphorylated ERK, which is a survival signal; moreover, during this process, there is no influence on NF-kappaB, Akt, p38, and Bcl-2. Diphosphonates 42-56 geranylgeranyl diphosphate synthase 1 Homo sapiens 89-102 13679234-12 2003 These results suggest that YM529, the new bisphosphonate, induced apoptosis when inhibit GGPP synthase and consequently decreased the levels of phosphorylated ERK, which is a survival signal; moreover, during this process, there is no influence on NF-kappaB, Akt, p38, and Bcl-2. Diphosphonates 42-56 mitogen-activated protein kinase 1 Homo sapiens 159-162 13679234-12 2003 These results suggest that YM529, the new bisphosphonate, induced apoptosis when inhibit GGPP synthase and consequently decreased the levels of phosphorylated ERK, which is a survival signal; moreover, during this process, there is no influence on NF-kappaB, Akt, p38, and Bcl-2. Diphosphonates 42-56 nuclear factor kappa B subunit 1 Homo sapiens 248-257 13679234-12 2003 These results suggest that YM529, the new bisphosphonate, induced apoptosis when inhibit GGPP synthase and consequently decreased the levels of phosphorylated ERK, which is a survival signal; moreover, during this process, there is no influence on NF-kappaB, Akt, p38, and Bcl-2. Diphosphonates 42-56 AKT serine/threonine kinase 1 Homo sapiens 259-262 13679234-12 2003 These results suggest that YM529, the new bisphosphonate, induced apoptosis when inhibit GGPP synthase and consequently decreased the levels of phosphorylated ERK, which is a survival signal; moreover, during this process, there is no influence on NF-kappaB, Akt, p38, and Bcl-2. Diphosphonates 42-56 mitogen-activated protein kinase 1 Homo sapiens 264-267 13679234-12 2003 These results suggest that YM529, the new bisphosphonate, induced apoptosis when inhibit GGPP synthase and consequently decreased the levels of phosphorylated ERK, which is a survival signal; moreover, during this process, there is no influence on NF-kappaB, Akt, p38, and Bcl-2. Diphosphonates 42-56 BCL2 apoptosis regulator Homo sapiens 273-278 12923892-7 2003 Compared to untreated OVX rats, the number of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts along the bone trabeculae in BP-administered OVX rats was not significantly decreased on days 14 and 30, but was significantly decreased on day 60. Diphosphonates 139-141 acid phosphatase 5, tartrate resistant Rattus norvegicus 46-81 12923892-7 2003 Compared to untreated OVX rats, the number of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts along the bone trabeculae in BP-administered OVX rats was not significantly decreased on days 14 and 30, but was significantly decreased on day 60. Diphosphonates 139-141 acid phosphatase 5, tartrate resistant Rattus norvegicus 83-87 14711309-7 2004 Since bisphosphonates are known to be potent, nanomolar inhibitors of the mevalonate/isoprene pathway enzyme farnesyl pyrophosphate synthase (FPPS), we also compared the pharmacophores for gammadelta T cell activation with those for FPPS inhibition, using the Catalyst program. Diphosphonates 6-21 farnesyl diphosphate synthase Homo sapiens 109-140 14711309-7 2004 Since bisphosphonates are known to be potent, nanomolar inhibitors of the mevalonate/isoprene pathway enzyme farnesyl pyrophosphate synthase (FPPS), we also compared the pharmacophores for gammadelta T cell activation with those for FPPS inhibition, using the Catalyst program. Diphosphonates 6-21 farnesyl diphosphate synthase Homo sapiens 142-146 14711309-9 2004 In addition, the CoMSIA fields were quite similar to those found for FPPS inhibition by bisphosphonates. Diphosphonates 88-103 farnesyl diphosphate synthase Homo sapiens 69-73 14711309-10 2004 The activities of the bisphosphonates in gammadelta T cell activation were highly correlated with their activities in FPPS inhibition: R = 0.88, p = 0.002, versus a human recombinant FPPS (N = 9 compounds); R = 0.82, p < 0.0001, for an expressed Leishmania major FPPS (N = 45 compounds). Diphosphonates 22-37 farnesyl diphosphate synthase Homo sapiens 118-122 15481635-7 2004 OC fragments were assayed in bone cell culture supernatants and in serum and urine from patients undergoing anti-resorptive bisphosphonate therapy using the Mid-OC urine ELISA. Diphosphonates 124-138 bone gamma-carboxyglutamate protein Homo sapiens 0-2 15481635-9 2004 Mid-OC values were decreased markedly after 3 and 10 days of anti-resorptive bisphosphonate treatment further indicating that the marker reflects bone resorption. Diphosphonates 77-91 bone gamma-carboxyglutamate protein Homo sapiens 4-6 14753746-0 2004 The nitrogen-containing bisphosphonate, zoledronic acid, influences RANKL expression in human osteoblast-like cells by activating TNF-alpha converting enzyme (TACE). Diphosphonates 24-38 TNF superfamily member 11 Homo sapiens 68-73 14753746-0 2004 The nitrogen-containing bisphosphonate, zoledronic acid, influences RANKL expression in human osteoblast-like cells by activating TNF-alpha converting enzyme (TACE). Diphosphonates 24-38 ADAM metallopeptidase domain 17 Homo sapiens 130-157 14753746-0 2004 The nitrogen-containing bisphosphonate, zoledronic acid, influences RANKL expression in human osteoblast-like cells by activating TNF-alpha converting enzyme (TACE). Diphosphonates 24-38 ADAM metallopeptidase domain 17 Homo sapiens 159-163 14753746-5 2004 MATERIALS AND METHODS: We examined the effect of the most potent nitrogen-containing BP available, zoledronic acid (ZOL), on the expression of RANKL and osteoprotegerin (OPG), critical factors in the regulation of OC formation and activation, in primary osteoblast (OB)-like cells derived from human bone, using flow cytometry, ELISA, semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR), in situ immunofluorescence staining, and Western blotting. Diphosphonates 85-87 TNF superfamily member 11 Homo sapiens 143-148 14753746-5 2004 MATERIALS AND METHODS: We examined the effect of the most potent nitrogen-containing BP available, zoledronic acid (ZOL), on the expression of RANKL and osteoprotegerin (OPG), critical factors in the regulation of OC formation and activation, in primary osteoblast (OB)-like cells derived from human bone, using flow cytometry, ELISA, semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR), in situ immunofluorescence staining, and Western blotting. Diphosphonates 85-87 TNF receptor superfamily member 11b Homo sapiens 153-168 14753746-5 2004 MATERIALS AND METHODS: We examined the effect of the most potent nitrogen-containing BP available, zoledronic acid (ZOL), on the expression of RANKL and osteoprotegerin (OPG), critical factors in the regulation of OC formation and activation, in primary osteoblast (OB)-like cells derived from human bone, using flow cytometry, ELISA, semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR), in situ immunofluorescence staining, and Western blotting. Diphosphonates 85-87 TNF receptor superfamily member 11b Homo sapiens 170-173 12923287-7 2004 Bisphosphonate treatment resulted in a decreased serum total alkaline phosphatase (serum tAP) level and QBS ratio, and also seemed to improve the complaints of the patients. Diphosphonates 0-14 nuclear RNA export factor 1 Homo sapiens 89-92 19379182-4 2003 Both BPs caused a significant (P < 0.001) dose-dependent increase in the proportion of cells undergoing apoptosis, as assessed both by cell-cycle analysis and by annexin-V binding. Diphosphonates 5-8 annexin A5 Homo sapiens 165-174 14620918-0 2003 Bisphosphonate induced growth inhibition of breast cancer cells is augmented by p38 inhibition. Diphosphonates 0-14 mitogen-activated protein kinase 14 Homo sapiens 80-83 14620918-6 2003 MDA-MB-231 cells stably expressing a dominant negative form of the p38 MAP kinase (p38/AF) exhibited a dramatic increase in growth inhibition in response to BPs in vitro, compared to control cells. Diphosphonates 157-160 mitogen-activated protein kinase 14 Homo sapiens 67-81 14620918-6 2003 MDA-MB-231 cells stably expressing a dominant negative form of the p38 MAP kinase (p38/AF) exhibited a dramatic increase in growth inhibition in response to BPs in vitro, compared to control cells. Diphosphonates 157-160 mitogen-activated protein kinase 14 Homo sapiens 67-70 14620918-7 2003 SB203580, a specific inhibitor of the p38 MAP kinase, also augmented BP-induced growth inhibition of parental MDA-MB-231 cells. Diphosphonates 69-71 mitogen-activated protein kinase 14 Homo sapiens 38-52 14620918-10 2003 In conclusion, these results suggest that BPs activate the p38 pathway in MDA-MB-231 and J774 cells. Diphosphonates 42-45 mitogen-activated protein kinase 14 Homo sapiens 59-62 14620918-11 2003 This activation may be associated with increased survival or proliferation because inhibition of p38 augments BP-induced growth inhibition. Diphosphonates 110-112 mitogen-activated protein kinase 14 Homo sapiens 97-100 12954450-0 2003 Regulation of MMP-9 (gelatinase B) in activated human monocyte/macrophages by two different types of bisphosphonates. Diphosphonates 101-116 matrix metallopeptidase 9 Homo sapiens 14-19 12868123-13 2003 Parathyroid hormone therapy results in increases in BMD that are even greater than estrogen and the bisphosphonates and to an even greater reduction in the risk of fractures, particularly non-vertebral fractures. Diphosphonates 100-115 parathyroid hormone Homo sapiens 0-19 12849976-0 2003 The bisphosphonate ibandronate stimulates reverse cholesterol transport out of monocytoid cells by enhanced ABCA1 transcription. Diphosphonates 4-18 ATP binding cassette subfamily A member 1 Homo sapiens 108-113 14499355-1 2003 The aim of this study was to investigate the cytotoxic activity of the third-generation nitrogen-containing bisphosphonate zoledronic acid (ZOL) as a single agent, and in combination with clinically relevant anticancer drugs, in a panel of human osteogenic sarcoma cell lines (HOS, BTK-143, MG-63, SJSA-1, G-292, and SAOS2). Diphosphonates 108-122 Bruton tyrosine kinase Homo sapiens 282-285 12799645-3 2003 Pancreatic cancer frequently has a dysregulated p21(ras) pathway and therefore appears to be a suitable target for BPs that interfere with the prenylation of small GTP-binding proteins such as p21(ras). Diphosphonates 115-118 H3 histone pseudogene 16 Homo sapiens 48-51 12838321-5 2003 We hypothesised that bisphosphonates could inhibit the favourable effects of "bone-derived" growth factors, and indeed found that bisphosphonates reduced or abolished the stimulatory effects of growth factors (IGFs, FGF-2) on MCF-7 and T47D cell proliferation and inhibited their protective effects on apoptotic cell death in vitro under serum-free conditions. Diphosphonates 130-145 fibroblast growth factor 2 Homo sapiens 216-221 12742232-6 2003 Checkpoint kinases, Chk1/2, and MAPK became phosphorylated after stimulation with bisphosphonates in the myeloma cells. Diphosphonates 82-97 checkpoint kinase 1 Homo sapiens 20-26 12799645-3 2003 Pancreatic cancer frequently has a dysregulated p21(ras) pathway and therefore appears to be a suitable target for BPs that interfere with the prenylation of small GTP-binding proteins such as p21(ras). Diphosphonates 115-118 H3 histone pseudogene 16 Homo sapiens 193-196 12732166-4 2003 In this review, we provide an overview of the RANK/RANKL/osteoprotegerin system; we describe its interaction with other cellular mechanisms, through which malignant plasma cells drive osteolysis, and explain how bisphosphonates can be used to block this action. Diphosphonates 212-227 TNF superfamily member 11 Homo sapiens 51-56 12771933-0 2003 New insights into the actions of bisphosphonate zoledronic acid in breast cancer cells by dual RhoA-dependent and -independent effects. Diphosphonates 33-47 ras homolog family member A Homo sapiens 95-99 12842447-3 2003 MATERIAL AND METHODS: We evaluated the effects of a bisphosphonate (clodronate) on MT1-MMP mRNA expression and protein production, catalytic activity and proteolytic activation of proMMP-2 by cultured human MG-63 osteosarcoma cells. Diphosphonates 52-66 matrix metallopeptidase 14 Homo sapiens 83-90 12842447-7 2003 CONCLUSION: We conclude that (1) the extracellular/cell-associated mechanism of bisphosphonate involves inhibition of MT1-MMP catalytic activity eventually by chelation, and that (2) intracellular mechanism involves downregulation of induced MT1-MMP mRNA and protein expression. Diphosphonates 80-94 matrix metallopeptidase 14 Homo sapiens 118-125 12842447-7 2003 CONCLUSION: We conclude that (1) the extracellular/cell-associated mechanism of bisphosphonate involves inhibition of MT1-MMP catalytic activity eventually by chelation, and that (2) intracellular mechanism involves downregulation of induced MT1-MMP mRNA and protein expression. Diphosphonates 80-94 matrix metallopeptidase 14 Homo sapiens 242-249 12732166-4 2003 In this review, we provide an overview of the RANK/RANKL/osteoprotegerin system; we describe its interaction with other cellular mechanisms, through which malignant plasma cells drive osteolysis, and explain how bisphosphonates can be used to block this action. Diphosphonates 212-227 TNF receptor superfamily member 11b Homo sapiens 57-72 12689676-3 2003 The present study showed that V-ATPase is directly involved in the incorporation of risedronate, a nitrogen containing bisphosphonate, into osteoclasts. Diphosphonates 119-133 ATPase, H+ transporting, lysosomal V0 subunit D2 Mus musculus 30-38 12689676-12 2003 These results suggest that V-ATPase induced acidification beneath the ruffled borders of osteoclasts and subsequent bone demineralization triggers the incorporation of both nitrogen-containing and non-nitrogen-containing bisphosphonates into osteoclasts. Diphosphonates 221-236 ATPase, H+ transporting, lysosomal V0 subunit D2 Mus musculus 27-35 12729778-11 2003 The patients with HHM who were administrated drugs such as bisphosphonate and calcitonin showed a reduction in their Ca and PTH-rP levels, and the six of ten EORTC QLQ-C30 subscales (emotional functioning, cognitive functioning, fatigue, dyspnoea, nausea/vomiting and appetite loss) were also improved after the anti-hypercalcemic therapy. Diphosphonates 59-73 cyclin D1 binding protein 1 Homo sapiens 18-21 12916277-6 2003 Estrogen and bisphosphonates stimulate the production of OPG that may, at least partly be responsible for their antirsorptive effect on bone. Diphosphonates 13-28 TNF receptor superfamily member 11b Homo sapiens 57-60 12729778-11 2003 The patients with HHM who were administrated drugs such as bisphosphonate and calcitonin showed a reduction in their Ca and PTH-rP levels, and the six of ten EORTC QLQ-C30 subscales (emotional functioning, cognitive functioning, fatigue, dyspnoea, nausea/vomiting and appetite loss) were also improved after the anti-hypercalcemic therapy. Diphosphonates 59-73 parathyroid hormone like hormone Homo sapiens 124-130 12509431-1 2003 We have previously reported dissociation constants for a range of bisphosphonate analogs of 1,3-bisphospho-D-glyceric acid binding to yeast phosphoglycerate kinase. Diphosphonates 66-80 phosphoglycerate kinase Saccharomyces cerevisiae S288C 140-163 12562045-8 2002 As a result of these biochemical effects on the mevalonate pathway, bisphosphonates appear to modulate the expression of bcl-2 leading to caspase-dependent apoptosis, inhibit matrix metalloproteinases, downregulate alphavbeta3 and alphavbeta5 integrins, and increase expression of osteoprotegerin, thereby antagonizing osteoclastogenesis. Diphosphonates 68-83 BCL2 apoptosis regulator Homo sapiens 121-126 12548581-10 2003 CONCLUSIONS: Bisphosphonates and Fc.OPG are effective inhibitors of the development of osteolytic bone lesions in pre-clinical murine models of myeloma bone disease. Diphosphonates 13-28 tumor necrosis factor receptor superfamily, member 11b (osteoprotegerin) Mus musculus 36-39 15775084-0 2003 [Bisphosphonate for GnRH therapy]. Diphosphonates 1-15 gonadotropin releasing hormone 1 Homo sapiens 20-24 15775084-3 2003 Bisphosphonate potently inhibits bone resorption, which subsequently inhibits elevated metabolic bone markers and osteopenia by GnRH therapy. Diphosphonates 0-14 gonadotropin releasing hormone 1 Homo sapiens 128-132 12632438-0 2003 Serum osteoprotegerin and its ligand in Paget"s disease of bone: relationship to disease activity and effect of treatment with bisphosphonates. Diphosphonates 127-142 TNF receptor superfamily member 11b Homo sapiens 6-21 12699303-8 2003 Treatment with calcitonin should be considered for older women with osteoporosis with painful vertebral fractures and for women who fail to respond to or cannot tolerate bisphosphonates. Diphosphonates 170-185 calcitonin related polypeptide alpha Homo sapiens 15-25 12699303-9 2003 Calcitonin may also be indicated for women who are unable to take bisphosphonates because of impaired renal function. Diphosphonates 66-81 calcitonin related polypeptide alpha Homo sapiens 0-10 14529538-5 2003 By contrast, the more potent, nitrogen-containing bisphosphonates (such as pamidronate, alendronate, risedronate, ibandronate and zoledronate) appear to act as analogues of isoprenoid diphosphate lipids, thereby inhibiting FPP synthase, an enzyme in the mevalonate pathway. Diphosphonates 50-65 farnesyl diphosphate synthase Homo sapiens 223-235 14529538-8 2003 Identification of FPP synthase as the target of nitrogen-containing bisphosphonates has also helped explain the molecular basis for the adverse effects of these agents in the GI tract and on the immune system. Diphosphonates 68-83 farnesyl diphosphate synthase Homo sapiens 18-30 12631257-12 2003 TRACP-5b has also proved to be a useful new marker for monitoring bisphosphonates treatment in MM. Diphosphonates 66-81 acid phosphatase 5, tartrate resistant Homo sapiens 0-8 12562045-8 2002 As a result of these biochemical effects on the mevalonate pathway, bisphosphonates appear to modulate the expression of bcl-2 leading to caspase-dependent apoptosis, inhibit matrix metalloproteinases, downregulate alphavbeta3 and alphavbeta5 integrins, and increase expression of osteoprotegerin, thereby antagonizing osteoclastogenesis. Diphosphonates 68-83 TNF receptor superfamily member 11b Homo sapiens 281-296 12177810-4 2002 Nitrogen-containing bisphosphonates were shown to inhibit farnesyl diphosphate synthase, thus blocking the synthesis of higher isoprenoids. Diphosphonates 20-35 farnesyl diphosphate synthase Homo sapiens 58-87 15046690-7 2002 In patients with metastatic prostate cancer, we are evaluating the addition of the bisphosphonate alendronate when added to ketoconazole for impact on matrix metalloproteinase (MMP)-2 and MMP-9 as well as traditional clinical endpoints. Diphosphonates 83-97 matrix metallopeptidase 2 Homo sapiens 151-183 12553014-4 2002 Here we evaluated the antitumor effects of a new bisphosphonate, the phenylacetate-bisphosphonate (PaBp), on human breast cancer MCF7 and MCF7-ras cell lines, both in vitro and in vivo. Diphosphonates 49-63 poly(A) binding protein cytoplasmic 1 Homo sapiens 99-103 12491800-4 2002 Gel shift assay using 32P-labeled OSE2 (osteoblast-specific cis-element 2: the consensus sequence for Cbfa1, refer to 2) indicated that TR (1 mM) increased the nuclear localization of Cbfa1, just as TPH (1-34) (3,4) and bisphosphonates did (5). Diphosphonates 220-235 RUNX family transcription factor 2 Rattus norvegicus 184-189 12014956-0 2002 Inhibition of geranylgeranyl diphosphate synthase by bisphosphonates and diphosphates: a potential route to new bone antiresorption and antiparasitic agents. Diphosphonates 53-68 geranylgeranyl diphosphate synthase 1 Homo sapiens 14-49 12119018-0 2002 The structure of PTP-1B in complex with a peptide inhibitor reveals an alternative binding mode for bisphosphonates. Diphosphonates 100-115 protein tyrosine phosphatase non-receptor type 1 Homo sapiens 17-23 12119018-8 2002 The crystal structure also revealed an unexpected binding orientation for a bisphosphonate inhibitor on PTP-1B, where the second difluorophosphonomethyl phenylalanine (F(2)PMP) moiety is bound close to Arg47 rather than in the previously identified second aryl phosphate site demarked by Arg24 and Arg254. Diphosphonates 76-90 protein tyrosine phosphatase non-receptor type 1 Homo sapiens 104-110 12096831-1 2002 We previously described the discovery of a fetuin-matrix Gla protein (MGP)-mineral complex in the serum of rats treated with the bone-active bisphosphonate etidronate and showed that the appearance of this complex in serum correlates with the inhibition of bone mineralization by etidronate. Diphosphonates 141-155 matrix Gla protein Rattus norvegicus 43-68 12096831-1 2002 We previously described the discovery of a fetuin-matrix Gla protein (MGP)-mineral complex in the serum of rats treated with the bone-active bisphosphonate etidronate and showed that the appearance of this complex in serum correlates with the inhibition of bone mineralization by etidronate. Diphosphonates 141-155 matrix Gla protein Rattus norvegicus 70-73 12109626-9 2002 In conclusion, we found that different bisphosphonates, currently used or tested in various clinical conditions, transiently stimulated the growth of preosteoblastic cells and thereafter increased their differentiation according to sequential events (type I collagen synthesis first, then ALP activity to a lesser extent). Diphosphonates 39-54 ATHS Homo sapiens 289-292 12014956-1 2002 We report the inhibition of a human recombinant geranylgeranyl diphosphate synthase (GGPPSase) by 23 bisphosphonates and six azaprenyl diphosphates. Diphosphonates 101-116 geranylgeranyl diphosphate synthase 1 Homo sapiens 48-83 12014956-1 2002 We report the inhibition of a human recombinant geranylgeranyl diphosphate synthase (GGPPSase) by 23 bisphosphonates and six azaprenyl diphosphates. Diphosphonates 101-116 geranylgeranyl diphosphate synthase 1 Homo sapiens 85-93 11984068-0 2002 Bisphosphonates inhibit stromelysin-1 (MMP-3), matrix metalloelastase (MMP-12), collagenase-3 (MMP-13) and enamelysin (MMP-20), but not urokinase-type plasminogen activator, and diminish invasion and migration of human malignant and endothelial cell lines. Diphosphonates 0-15 matrix metallopeptidase 20 Homo sapiens 119-125 12038623-1 2002 This study examined the inhibitory effect of a new bisphosphonate (TRK-530) on wear debris-mediated bone resorption in a rat osteolysis model involving continuous infusion of high density polyethylene (HDPE) particles. Diphosphonates 51-65 neurotrophic receptor tyrosine kinase 1 Rattus norvegicus 67-74 12038623-2 2002 TRK-530 (TRK) is a novel synthetic bisphosphonate that has been shown to decrease the level of tumor necrosis factor alpha (TNF-alpha) in the bone marrow of rats with adjuvant arthritis. Diphosphonates 35-49 neurotrophic receptor tyrosine kinase 1 Rattus norvegicus 0-7 12038623-2 2002 TRK-530 (TRK) is a novel synthetic bisphosphonate that has been shown to decrease the level of tumor necrosis factor alpha (TNF-alpha) in the bone marrow of rats with adjuvant arthritis. Diphosphonates 35-49 neurotrophic receptor tyrosine kinase 1 Rattus norvegicus 0-3 11741942-1 2002 Bisphosphonates, drugs used widely in the treatment of bone diseases, prevent osteoblast and osteocyte apoptosis by a mechanism involving extracellular signal-regulated kinase (ERK) activation. Diphosphonates 0-15 mitogen-activated protein kinase 1 Homo sapiens 138-175 11741942-1 2002 Bisphosphonates, drugs used widely in the treatment of bone diseases, prevent osteoblast and osteocyte apoptosis by a mechanism involving extracellular signal-regulated kinase (ERK) activation. Diphosphonates 0-15 mitogen-activated protein kinase 1 Homo sapiens 177-180 11741942-2 2002 We report herein that hexameric connexin (Cx)-43 hemichannels, but not gap junctions, are the essential transducers of the ERK-activating/anti-apoptotic effects of bisphosphonates. Diphosphonates 164-179 mitogen-activated protein kinase 1 Homo sapiens 123-126 11984068-0 2002 Bisphosphonates inhibit stromelysin-1 (MMP-3), matrix metalloelastase (MMP-12), collagenase-3 (MMP-13) and enamelysin (MMP-20), but not urokinase-type plasminogen activator, and diminish invasion and migration of human malignant and endothelial cell lines. Diphosphonates 0-15 matrix metallopeptidase 3 Homo sapiens 24-37 11984068-0 2002 Bisphosphonates inhibit stromelysin-1 (MMP-3), matrix metalloelastase (MMP-12), collagenase-3 (MMP-13) and enamelysin (MMP-20), but not urokinase-type plasminogen activator, and diminish invasion and migration of human malignant and endothelial cell lines. Diphosphonates 0-15 matrix metallopeptidase 3 Homo sapiens 39-44 11984068-0 2002 Bisphosphonates inhibit stromelysin-1 (MMP-3), matrix metalloelastase (MMP-12), collagenase-3 (MMP-13) and enamelysin (MMP-20), but not urokinase-type plasminogen activator, and diminish invasion and migration of human malignant and endothelial cell lines. Diphosphonates 0-15 matrix metallopeptidase 12 Homo sapiens 71-77 11984068-0 2002 Bisphosphonates inhibit stromelysin-1 (MMP-3), matrix metalloelastase (MMP-12), collagenase-3 (MMP-13) and enamelysin (MMP-20), but not urokinase-type plasminogen activator, and diminish invasion and migration of human malignant and endothelial cell lines. Diphosphonates 0-15 matrix metallopeptidase 13 Homo sapiens 80-101 11986784-0 2002 The bisphosphonate zoledronic acid impairs Ras membrane [correction of impairs membrane] localisation and induces cytochrome c release in breast cancer cells. Diphosphonates 4-18 cytochrome c, somatic Homo sapiens 114-126 11986784-3 2002 Nitrogen-containing bisphosphonates including zoledronic acid have been shown to induce apoptosis associated with PARP cleavage and DNA fragmentation. Diphosphonates 20-35 collagen type XI alpha 2 chain Homo sapiens 114-118 11986784-5 2002 Forced expression of the anti-apoptotic protein bcl-2 attenuated bisphosphonate-induced loss of cell viability and induction of DNA fragmentation in MDA-MB-231 cells. Diphosphonates 65-79 BCL2 apoptosis regulator Homo sapiens 48-53 11906826-7 2002 Bisphosphonates also elicited an increase in numbers of osteoblast (82%) and restored alkaline phosphatase (ALP) activity, which was reduced by 15% (P approximately equal to 0.05) compared to control levels. Diphosphonates 0-15 alkaline phosphatase, placental Homo sapiens 86-106 11906826-7 2002 Bisphosphonates also elicited an increase in numbers of osteoblast (82%) and restored alkaline phosphatase (ALP) activity, which was reduced by 15% (P approximately equal to 0.05) compared to control levels. Diphosphonates 0-15 alkaline phosphatase, placental Homo sapiens 108-111 12038623-2 2002 TRK-530 (TRK) is a novel synthetic bisphosphonate that has been shown to decrease the level of tumor necrosis factor alpha (TNF-alpha) in the bone marrow of rats with adjuvant arthritis. Diphosphonates 35-49 tumor necrosis factor Rattus norvegicus 95-122 12038623-2 2002 TRK-530 (TRK) is a novel synthetic bisphosphonate that has been shown to decrease the level of tumor necrosis factor alpha (TNF-alpha) in the bone marrow of rats with adjuvant arthritis. Diphosphonates 35-49 tumor necrosis factor Rattus norvegicus 124-133 12005179-0 2002 Effect of intravenous bisphosphonates on release of basic fibroblast growth factor in serum of patients with cancer-associated hypercalcemia. Diphosphonates 22-37 fibroblast growth factor 2 Homo sapiens 52-82 12005179-2 2002 We examined the effects of acute administration of intravenous bisphosphonates on release of bFGF in human serum. Diphosphonates 63-78 fibroblast growth factor 2 Homo sapiens 93-97 12005179-4 2002 Nearly all twelve patients with elevated baseline serum bFGF ranging from 5-27 pg/mL showed significant decreases in serum bFGF (2-7 days) after iv bisphosphonate treatment. Diphosphonates 148-162 fibroblast growth factor 2 Homo sapiens 56-60 12005179-4 2002 Nearly all twelve patients with elevated baseline serum bFGF ranging from 5-27 pg/mL showed significant decreases in serum bFGF (2-7 days) after iv bisphosphonate treatment. Diphosphonates 148-162 fibroblast growth factor 2 Homo sapiens 123-127 12005179-9 2002 Acute change in low serum levels of bFGF in patients with cancer-associated hypercalcemia treated with intravenous bisphosphonates may be physiologically inversely regulated by acute change in the serum calcium concentration. Diphosphonates 115-130 fibroblast growth factor 2 Homo sapiens 36-40 11984068-1 2002 Bisphosphonates (clodronate, alendronate, pamidronate and zoledronate) at therapeutically attainable non-cytotoxic concentrations inhibited MMP-3, -12, -13 and -20 as well as MMP-1, -2, -8 and -9, but not urokinase-type plasminogen activator (uPA), a serine proteinase and a pro-MMP activator. Diphosphonates 0-15 matrix metallopeptidase 3 Homo sapiens 140-163 11984068-1 2002 Bisphosphonates (clodronate, alendronate, pamidronate and zoledronate) at therapeutically attainable non-cytotoxic concentrations inhibited MMP-3, -12, -13 and -20 as well as MMP-1, -2, -8 and -9, but not urokinase-type plasminogen activator (uPA), a serine proteinase and a pro-MMP activator. Diphosphonates 0-15 matrix metallopeptidase 1 Homo sapiens 175-195 11984068-1 2002 Bisphosphonates (clodronate, alendronate, pamidronate and zoledronate) at therapeutically attainable non-cytotoxic concentrations inhibited MMP-3, -12, -13 and -20 as well as MMP-1, -2, -8 and -9, but not urokinase-type plasminogen activator (uPA), a serine proteinase and a pro-MMP activator. Diphosphonates 0-15 plasminogen activator, urokinase Homo sapiens 205-241 11920416-8 2002 CONCLUSION: These data suggest that OPG alone or in combination with bisphosphonates is an effective therapeutic tool for the prevention of TNF alpha-mediated destruction of bone by reducing the number of bone-resorbing cells in the inflammatory tissue. Diphosphonates 69-84 tumor necrosis factor Mus musculus 140-149 11984068-1 2002 Bisphosphonates (clodronate, alendronate, pamidronate and zoledronate) at therapeutically attainable non-cytotoxic concentrations inhibited MMP-3, -12, -13 and -20 as well as MMP-1, -2, -8 and -9, but not urokinase-type plasminogen activator (uPA), a serine proteinase and a pro-MMP activator. Diphosphonates 0-15 plasminogen activator, urokinase Homo sapiens 243-246 11984068-8 2002 Bisphosphonates are broad-spectrum MMP inhibitors and this inhibition involves cation chelation. Diphosphonates 0-15 matrix metallopeptidase 1 Homo sapiens 35-38 11855844-0 2002 Bisphosphonates pamidronate and zoledronic acid stimulate osteoprotegerin production by primary human osteoblasts. Diphosphonates 0-15 TNF receptor superfamily member 11b Homo sapiens 58-73 11855844-5 2002 In this study, we assessed the effects of the bisphosphonates pamidronate (PAM) and zoledronic acid (ZOL) on OPG mRNA steady-state levels (by semiquantitative RT-PCR) and protein production (by ELISA) in primary human osteoblasts (hOB). Diphosphonates 46-61 TNF receptor superfamily member 11b Homo sapiens 109-112 12560590-8 2002 In experiments using levamisole, an alkaline phosphatase inhibitor, and DMDP, a bisphosphonate, both inhibitors inhibited down-regulation during beta-GP-induced calcification, suggesting that the down-regulation of TE, FBN1, and LO directly relates to calcium deposition. Diphosphonates 80-94 elastin Bos taurus 215-217 11855844-10 2002 In conclusion, our data suggest that bisphosphonates modulate OPG production by normal human osteoblasts, which may contribute to the inhibition of osteoclastic bone resorption. Diphosphonates 37-52 TNF receptor superfamily member 11b Homo sapiens 62-65 11855844-11 2002 Since, OPG production increases with osteoblastic cell maturation, enhancement of OPG by bisphosphonates could be related to their stimulatory effects on osteoblastic differentiation. Diphosphonates 89-104 TNF receptor superfamily member 11b Homo sapiens 7-10 11855844-11 2002 Since, OPG production increases with osteoblastic cell maturation, enhancement of OPG by bisphosphonates could be related to their stimulatory effects on osteoblastic differentiation. Diphosphonates 89-104 TNF receptor superfamily member 11b Homo sapiens 82-85 11785983-0 2002 Identification of a bisphosphonate that inhibits isopentenyl diphosphate isomerase and farnesyl diphosphate synthase. Diphosphonates 20-34 farnesyl diphosphate synthase Homo sapiens 87-116 11785983-1 2002 We and others have recently shown that the major molecular target of nitrogen-containing bisphosphonate drugs is farnesyl diphosphate synthase, an enzyme in the mevalonate pathway. Diphosphonates 89-103 farnesyl diphosphate synthase Homo sapiens 113-142 11785983-2 2002 In an in vitro screen, we discovered a bisphosphonate, NE21650, that potently inhibited farnesyl diphosphate synthase but, unlike other N-BPs investigated, was also a weak inhibitor of isopentenyl diphosphate isomerase. Diphosphonates 39-53 farnesyl diphosphate synthase Homo sapiens 88-117 11785983-4 2002 Our observations show that minor changes to the structure of bisphosphonates allow inhibition of more than one enzyme in the mevalonate pathway and suggest that loss of protein prenylation due to inhibition of more than one enzyme in the mevalonate pathway may lead to an increase in antiresorptive potency compared to bisphosphonates that only inhibit farnesyl diphosphate synthase. Diphosphonates 61-76 farnesyl diphosphate synthase Homo sapiens 353-382 11792566-1 2002 Nitrogen-containing bisphosphonates (NBps) are taken up by osteoclasts and inhibit farnesyl pyrophosphate synthase, an enzyme of the mevalonate pathway. Diphosphonates 20-35 farnesyl diphosphate synthetase Mus musculus 83-114 11581260-1 2001 Nitrogen-containing bisphosphonate drugs inhibit bone resorption by inhibiting FPP synthase and thereby preventing the synthesis of isoprenoid lipids required for protein prenylation in bone-resorbing osteoclasts. Diphosphonates 20-34 farnesyl diphosphate synthetase Mus musculus 79-91 11741801-8 2001 During treatment with bisphosphonates, elevated plasma levels of PTHrP are associated with a weak response. Diphosphonates 22-37 parathyroid hormone like hormone Homo sapiens 65-70 11344045-0 2001 Visualization of bisphosphonate-induced caspase-3 activity in apoptotic osteoclasts in vitro. Diphosphonates 17-31 caspase 3 Homo sapiens 40-49 11697801-5 2001 Osteoblast proliferation induced by all BPs diminished to control levels in the presence of U0126, a specific inhibitor of the upstream kinase MEK 1 responsible for ERK phosphorylation. Diphosphonates 40-43 mitogen activated protein kinase kinase 1 Rattus norvegicus 143-148 11697801-5 2001 Osteoblast proliferation induced by all BPs diminished to control levels in the presence of U0126, a specific inhibitor of the upstream kinase MEK 1 responsible for ERK phosphorylation. Diphosphonates 40-43 Eph receptor B1 Rattus norvegicus 165-168 11697801-6 2001 Consistent with this, BPs induced ERK activation as assessed by in-gel kinase assays. Diphosphonates 22-25 Eph receptor B1 Rattus norvegicus 34-37 11697801-7 2001 Phosphorylation of ERK1/2 was induced by the BPs olpadronate and pamidronate within 30 s, followed by rapid dephosphorylation, whereas etidronate induced phosphorylation of ERKs only after 90 s of incubation and returned to basal levels within 15-30 minutes. Diphosphonates 45-48 mitogen activated protein kinase 3 Rattus norvegicus 19-25 11697801-8 2001 In addition, both BP-induced cell proliferation and ERK phosphorylation were reduced to basal levels in the presence of nifedipine, an L-type voltage-sensitive calcium channel (VSCC) inhibitor. Diphosphonates 18-20 Eph receptor B1 Rattus norvegicus 52-55 11697801-9 2001 These results show that BP-induced proliferation of osteoblastic cells is mediated by activation of ERKs and suggest that this effect requires influx of Ca2+ from the extracellular space through calcium channels. Diphosphonates 24-26 mitogen activated protein kinase 3 Rattus norvegicus 100-104 11602851-17 2001 CONCLUSIONS: Antiresorptive therapy with a bisphosphonate decreases the fracture rate and preserves bone mass 1 year after lung transplantation. Diphosphonates 43-57 adhesion G protein-coupled receptor V1 Homo sapiens 105-111 11425649-0 2001 Bisphosphonate acts on osteoclasts independent of ruffled borders in osteosclerotic (oc/oc) mice. Diphosphonates 0-14 T cell, immune regulator 1, ATPase, H+ transporting, lysosomal V0 protein A3 Mus musculus 69-91 11425649-1 2001 We examined the effects of a third generation bisphosphonate [YM-175; disodium dihydrogen (cycloheptylamino)-methylene-1,1-bisphosphonate] on osteoclasts in osteosclerotic (oc/oc) mice to elucidate the cellular mechanism for incorporation of the bisphosphonate. Diphosphonates 46-60 T cell, immune regulator 1, ATPase, H+ transporting, lysosomal V0 protein A3 Mus musculus 157-179 11344045-8 2001 Caspase-3, therefore, appears to be the major effector caspase activated in osteoclasts by bisphosphonate treatment. Diphosphonates 91-105 caspase 3 Homo sapiens 0-9 11344045-6 2001 Bisphosphonate-induced osteoclast apoptosis was dependent on caspase activation, because apoptosis resulting from alendronate, clodronate, or zoledronic acid treatment was suppressed by zVAD-fmk, a broad-range caspase inhibitor, or by SB-281277, a specific isatin sulfonamide inhibitor of caspase-3/-7. Diphosphonates 0-14 caspase 3 Homo sapiens 289-301 11344045-9 2001 Caspase activation and apoptosis induced by nitrogen-containing bisphosphonates are likely to be the consequence of the loss of geranylgeranylated rather than farnesylated proteins, because the ability to cause apoptosis and caspase activation was mimicked by GGTI-298, a specific inhibitor of protein geranylgeranylation, whereas FTI-277, a specific inhibitor of protein farnesylation, had no effect on apoptosis or caspase activity. Diphosphonates 64-79 protein geranylgeranyltransferase type I subunit beta Homo sapiens 260-264 11160603-6 2001 Furthermore, minor changes to the structure of the R(2) side chain of heterocycle-containing bisphosphonates, giving rise to less potent inhibitors of bone resorption in vivo, also caused a reduction in potency up to approximately 300-fold for inhibition of farnesyl diphosphate synthase in vitro. Diphosphonates 93-108 farnesyl diphosphate synthase Homo sapiens 258-287 11430477-6 2001 4) BPs promoted luciferase expression in murine p1.3-osteocalcin gene 2-luc and p6-osteoblast specific element 2-luc transfected cells, just as MVA, FPP and GGPP did independently and additively to INC. 5) BPs activated extracellular signal-regulated kinase (ERK1/2) in a Ras-independent manner within 5 min, and Pi was found to sensitize MC4 cells to BPs. Diphosphonates 3-6 bone gamma-carboxyglutamate protein 2 Mus musculus 53-64 11430477-6 2001 4) BPs promoted luciferase expression in murine p1.3-osteocalcin gene 2-luc and p6-osteoblast specific element 2-luc transfected cells, just as MVA, FPP and GGPP did independently and additively to INC. 5) BPs activated extracellular signal-regulated kinase (ERK1/2) in a Ras-independent manner within 5 min, and Pi was found to sensitize MC4 cells to BPs. Diphosphonates 3-6 mitogen-activated protein kinase 3 Mus musculus 259-265 11430477-9 2001 The results suggest that BPs act on Pi-sensitized MC4 cells to accelerate mineralization via nonRas-MEK-ERK1/2-Cbfa1 transactivation pathway and INC additionally acts by inhibiting the MVA pathway. Diphosphonates 25-28 mitogen-activated protein kinase kinase 7 Homo sapiens 100-103 11430477-9 2001 The results suggest that BPs act on Pi-sensitized MC4 cells to accelerate mineralization via nonRas-MEK-ERK1/2-Cbfa1 transactivation pathway and INC additionally acts by inhibiting the MVA pathway. Diphosphonates 25-28 mitogen-activated protein kinase 3 Homo sapiens 104-110 11430477-9 2001 The results suggest that BPs act on Pi-sensitized MC4 cells to accelerate mineralization via nonRas-MEK-ERK1/2-Cbfa1 transactivation pathway and INC additionally acts by inhibiting the MVA pathway. Diphosphonates 25-28 RUNX family transcription factor 2 Homo sapiens 111-116 11354395-9 2001 Newer bisphosphonates such as alendronate and risedronate provide significant therapeutic advantages over etidronate, both in the extent of reduction in bone-specific alkaline phosphatase (BSAP) and/or total serum alkaline phosphatase (SAP) and in the duration of remission, as measured by normalization of BSAP/SAP. Diphosphonates 6-21 paired box 5 Homo sapiens 153-187 11354395-9 2001 Newer bisphosphonates such as alendronate and risedronate provide significant therapeutic advantages over etidronate, both in the extent of reduction in bone-specific alkaline phosphatase (BSAP) and/or total serum alkaline phosphatase (SAP) and in the duration of remission, as measured by normalization of BSAP/SAP. Diphosphonates 6-21 paired box 5 Homo sapiens 189-193 11354395-9 2001 Newer bisphosphonates such as alendronate and risedronate provide significant therapeutic advantages over etidronate, both in the extent of reduction in bone-specific alkaline phosphatase (BSAP) and/or total serum alkaline phosphatase (SAP) and in the duration of remission, as measured by normalization of BSAP/SAP. Diphosphonates 6-21 amyloid P component, serum Homo sapiens 190-193 11354395-9 2001 Newer bisphosphonates such as alendronate and risedronate provide significant therapeutic advantages over etidronate, both in the extent of reduction in bone-specific alkaline phosphatase (BSAP) and/or total serum alkaline phosphatase (SAP) and in the duration of remission, as measured by normalization of BSAP/SAP. Diphosphonates 6-21 paired box 5 Homo sapiens 307-311 11354395-9 2001 Newer bisphosphonates such as alendronate and risedronate provide significant therapeutic advantages over etidronate, both in the extent of reduction in bone-specific alkaline phosphatase (BSAP) and/or total serum alkaline phosphatase (SAP) and in the duration of remission, as measured by normalization of BSAP/SAP. Diphosphonates 6-21 amyloid P component, serum Homo sapiens 236-239 11160603-2 2001 Recently, several nitrogen-containing bisphosphonates were found to inhibit osteoclast-mediated bone resorption in vitro by inhibiting farnesyl diphosphate synthase, thereby preventing protein prenylation in osteoclasts. Diphosphonates 38-53 farnesyl diphosphate synthase Homo sapiens 135-164 11707147-4 2001 Administration of PTH in combination with antiresorptive agents such as estrogen, calcitonin, vitamin D and bisphosphonates augments its effect. Diphosphonates 108-123 parathyroid hormone Homo sapiens 18-21 11716232-2 2001 Elevation of the serum marker calcitonin coincided with the introduction of biphosphonate therapy and recurrence of tumour was not established. Diphosphonates 76-89 calcitonin related polypeptide alpha Homo sapiens 30-40 12064622-0 2001 Bisphosphonate-induced, hemichannel-mediated, anti-apoptosis through the Src/ERK pathway: a gap junction-independent action of connexin43. Diphosphonates 0-14 Rous sarcoma oncogene Mus musculus 73-76 12064622-0 2001 Bisphosphonate-induced, hemichannel-mediated, anti-apoptosis through the Src/ERK pathway: a gap junction-independent action of connexin43. Diphosphonates 0-14 mitogen-activated protein kinase 1 Mus musculus 77-80 12064622-0 2001 Bisphosphonate-induced, hemichannel-mediated, anti-apoptosis through the Src/ERK pathway: a gap junction-independent action of connexin43. Diphosphonates 0-14 gap junction protein, alpha 1 Mus musculus 127-137 12064622-2 2001 We report herein a mechanism by which connexin43 hemichannel opening by bisphosphonates triggers the activation of the kinases Src and ERKs and promotes cell survival. Diphosphonates 72-87 gap junction protein, alpha 1 Mus musculus 38-48 12064622-2 2001 We report herein a mechanism by which connexin43 hemichannel opening by bisphosphonates triggers the activation of the kinases Src and ERKs and promotes cell survival. Diphosphonates 72-87 Rous sarcoma oncogene Mus musculus 127-130 12064622-2 2001 We report herein a mechanism by which connexin43 hemichannel opening by bisphosphonates triggers the activation of the kinases Src and ERKs and promotes cell survival. Diphosphonates 72-87 mitogen-activated protein kinase 1 Mus musculus 135-139 12064622-5 2001 The anti-apoptotic effect of bisphosphonates depends on connexin43 expression in mouse embryonic fibroblasts and osteoblastic cells. Diphosphonates 29-44 gap junction protein, alpha 1 Mus musculus 56-66 12064622-9 2001 These studies establish a role for connexin43 hemichannels in bisphosphonate action, and a novel function of connexin43--beyond gap junction communication--in the regulation of survival signaling pathways. Diphosphonates 62-76 gap junction protein, alpha 1 Mus musculus 35-45 11716232-3 2001 The interaction of biphosphonates with calcitonin is not previously recorded. Diphosphonates 19-33 calcitonin related polypeptide alpha Homo sapiens 39-49 11149474-4 2001 Bisphosphonates are capable of suppressing parathyroid hormone (PTH)-mediated bone resorption and are useful for the prevention and treatment of postmenopausal osteoporosis. Diphosphonates 0-15 parathyroid hormone Homo sapiens 43-62 10967538-0 2000 Bisphosphonate administration alters subcellular localization of vacuolar-type H(+)-ATPase and cathepsin K in osteoclasts during experimental movement of rat molars. Diphosphonates 0-14 cathepsin K Rattus norvegicus 95-106 11108295-2 2000 In vitro studies indicate that the clinically used nitrogen-containing bisphosphonates (N-BPs) such as alendronate (ALN), risedronate (RIS) and ibandronate (IBA) suppress bone resorption via inhibition of the mevalonate pathway enzyme farnesyl diphosphate (FPP) synthase in osteoclasts (Ocs). Diphosphonates 71-86 farnesyl diphosphate synthase Rattus norvegicus 235-270 11020278-1 2000 This work was aimed at improving the absorption of bisphosphonates by targeting carrier systems in the intestine and the intestinal peptide carrier system (hPEPT1), in particular. Diphosphonates 51-66 solute carrier family 15 member 1 Homo sapiens 156-162 11020278-6 2000 The results indicate that the oral absorption of bisphosphonates can be improved by peptidyl prodrugs via the hPEPT1; however, other transporters may also be involved. Diphosphonates 49-64 solute carrier family 15 member 1 Homo sapiens 110-116 10958874-9 2000 After treatment by bisphosphonates, the fall in CTX concentrations was paralleled to urinary calcium and more marked than pyridinolines. Diphosphonates 19-34 cytochrome P450 family 27 subfamily A member 1 Homo sapiens 48-51 11211310-0 2000 Effects of bisphosphonate on the release of MMP-2 from cultured human osteoblasts. Diphosphonates 11-25 matrix metallopeptidase 2 Homo sapiens 44-49 11211310-2 2000 We investigated the role of bisphosphonates, potent inhibitors of bone resorption, on the production of MMP-2 from human osteoblasts. Diphosphonates 28-43 matrix metallopeptidase 2 Homo sapiens 104-109 11211310-4 2000 However, in the presence of physiological concentrations of plasmin, bisphosphonates reduced the amount of MMP-2 in osteoblasts-conditioned media. Diphosphonates 69-84 plasminogen Homo sapiens 60-67 11211310-4 2000 However, in the presence of physiological concentrations of plasmin, bisphosphonates reduced the amount of MMP-2 in osteoblasts-conditioned media. Diphosphonates 69-84 matrix metallopeptidase 2 Homo sapiens 107-112 11211310-5 2000 Furthermore, bisphosphonates treatment induced degradation of MMP-2 in the presence of plasmin. Diphosphonates 13-28 matrix metallopeptidase 2 Homo sapiens 62-67 11211310-5 2000 Furthermore, bisphosphonates treatment induced degradation of MMP-2 in the presence of plasmin. Diphosphonates 13-28 plasminogen Homo sapiens 87-94 11211310-6 2000 Our results indicated that bisphosphonate, a divalent cation chelator, negatively regulated the longevity of MMP-2 in soluble phase plasmin-containing environment. Diphosphonates 27-41 matrix metallopeptidase 2 Homo sapiens 109-114 11211310-6 2000 Our results indicated that bisphosphonate, a divalent cation chelator, negatively regulated the longevity of MMP-2 in soluble phase plasmin-containing environment. Diphosphonates 27-41 plasminogen Homo sapiens 132-139 11211310-7 2000 These findings suggest that bisphosphonates inhibit bone resorption by abrogating MMP-2 protection induced by plasmin-mediated degradation. Diphosphonates 28-43 matrix metallopeptidase 2 Homo sapiens 82-87 11211310-7 2000 These findings suggest that bisphosphonates inhibit bone resorption by abrogating MMP-2 protection induced by plasmin-mediated degradation. Diphosphonates 28-43 plasminogen Homo sapiens 110-117 10967538-7 2000 Subcellular localization and expression of both vacuolar-type H(+)-ATPase and cathepsin K was significantly decreased in such osteoclasts with impaired ruffled borders and/or only clear zones by BP administration. Diphosphonates 195-197 cathepsin K Rattus norvegicus 78-89 10967538-8 2000 In particular, cathepsin K secretion by osteoclasts towards resorption lacunae was markedly inhibited by BP administration. Diphosphonates 105-107 cathepsin K Rattus norvegicus 15-26 10967538-9 2000 Our results indicate for the first time that BP administration significantly impair the osteoclast structure and reduces expression of both vacuolar-type H(+)-ATPase and cathepsin K in osteoclasts during tooth movement. Diphosphonates 45-47 cathepsin K Rattus norvegicus 170-181 12057049-10 2000 We use bisphosphonates in patients with bone lesions or osteoporosis or when there is a progressive rise in M-protein. Diphosphonates 7-22 myomesin 2 Homo sapiens 108-117 10994783-2 2000 After the administration of bisphosphonate to 6-day-old rabbits, many odontoclasts detached from the dentine surface of the deciduous teeth, resulting in the reduction of tartrate-resistant acid phosphatase (TRAP-ase) and immunoreactivity for cathepsin K. Diphosphonates 28-42 cathepsin K Oryctolagus cuniculus 243-254 10994783-7 2000 Thus, odontoclasts are able to undergo apoptosis after bisphosphonate treatment; this results in cytological alterations, including reduced resorption activity and the inhibition of protein synthesis/transport as indicated by the diminished TRAPase and cathepsin K and the poorly developed Golgi apparatus, respectively. Diphosphonates 55-69 cathepsin K Oryctolagus cuniculus 253-264 10960024-15 2000 These effects appear to occur without altering either mRNA or protein levels for these enzymes, supporting a possible mechanism of action that involves the ability of bisphosphonates to chelate cations from the MMPs. Diphosphonates 167-182 matrix metallopeptidase 1 Homo sapiens 211-215 10925751-9 2000 There is also an increase in interleukin-6-induced osteoclastic bone resorption, which is the rationale for treating these patients with bisphosphonates. Diphosphonates 137-152 interleukin 6 Homo sapiens 29-42 10773591-12 2000 Sixteen of 17 (94%) of the HRT-treated and 12 of 13 (92%) of the bisphosphonate-treated women showed a decrease in serum CTx after 6 months that was greater than the calculated least significant change (LSC) of the marker (LSC(CTx)). Diphosphonates 65-79 cytochrome P450 family 27 subfamily A member 1 Homo sapiens 121-124 10773591-12 2000 Sixteen of 17 (94%) of the HRT-treated and 12 of 13 (92%) of the bisphosphonate-treated women showed a decrease in serum CTx after 6 months that was greater than the calculated least significant change (LSC) of the marker (LSC(CTx)). Diphosphonates 65-79 cytochrome P450 family 27 subfamily A member 1 Homo sapiens 227-230 10620064-10 1999 In conclusion, the apoptosis of myeloma cells and BMSCs and the inhibition of both IL-6 and MMP-1 production induced by bisphosphonates, mainly zoledronate, could have antitumoral effects in patients with MM. Diphosphonates 120-135 interleukin 6 Homo sapiens 83-87 10652955-0 2000 Serum CTX: a new marker of bone resorption that shows treatment effect more often than other markers because of low coefficient of variability and large changes with bisphosphonate therapy. Diphosphonates 166-180 cytochrome P450 family 27 subfamily A member 1 Homo sapiens 6-9 10620343-9 2000 These findings (i) identify farnesyl diphosphate synthase as the selective target of alendronate in the mevalonate pathway, (ii) show that this enzyme is inhibited by other N-containing bisphosphonates, such as risendronate, but not by clodronate, supporting a different mechanism of action for different bisphosphonates, and (iii) document in purified osteoclasts alendronate inhibition of prenylation and sterol biosynthesis. Diphosphonates 186-201 farnesyl diphosphate synthase Homo sapiens 28-57 10632320-17 1999 Breast cancer patients with elevated serum BSP levels may benefit from osteoprotective adjuvant therapy with bisphosphonates. Diphosphonates 109-124 integrin binding sialoprotein Homo sapiens 43-46 10574973-0 1999 Bisphosphonates act directly on the osteoclast to induce caspase cleavage of mst1 kinase during apoptosis. Diphosphonates 0-15 macrophage stimulating 1 Homo sapiens 77-81 10620064-10 1999 In conclusion, the apoptosis of myeloma cells and BMSCs and the inhibition of both IL-6 and MMP-1 production induced by bisphosphonates, mainly zoledronate, could have antitumoral effects in patients with MM. Diphosphonates 120-135 matrix metallopeptidase 1 Homo sapiens 92-97 10527849-0 1999 Farnesyl pyrophosphate synthase is the molecular target of nitrogen-containing bisphosphonates. Diphosphonates 79-94 farnesyl pyrophosphate synthase Bos taurus 0-31 10527849-2 1999 Recent evidence indicated that farnesyl pyrophosphate (FPP) synthase and/or isopentenyl pyrophosphate (IPP) isomerase is the intracellular target(s) of bisphosphonate action. Diphosphonates 152-166 farnesyl pyrophosphate synthase Bos taurus 31-68 10049736-0 1999 Nitrogen-containing bisphosphonates inhibit isopentenyl pyrophosphate isomerase/farnesyl pyrophosphate synthase activity with relative potencies corresponding to their antiresorptive potencies in vitro and in vivo. Diphosphonates 20-35 farnesyl diphosphate synthase Homo sapiens 80-111 10430650-4 1999 However, a simultaneous 8-week administration of conjugated estrogens, bisphosphonate, and vitamin D(3) analog markedly augmented the BMC values to 110.3%, 110.1%, and 114.4%, respectively, of those in the rats treated with the GnRH agonist alone. Diphosphonates 71-85 gonadotropin releasing hormone 1 Rattus norvegicus 228-232 10415748-4 1999 We have discovered that various matrix metalloproteinases (MMPs) are inhibited in vitro by several bisphosphonates. Diphosphonates 99-114 matrix metallopeptidase 1 Homo sapiens 59-63 10413987-13 1999 The biphosphonates, etidronate and ibendronate significantly reduced the TNF response of the PE-stimulated macrophages (by 1/7 and 1/5, respectively). Diphosphonates 4-18 tumor necrosis factor Homo sapiens 73-76 10413987-13 1999 The biphosphonates, etidronate and ibendronate significantly reduced the TNF response of the PE-stimulated macrophages (by 1/7 and 1/5, respectively). Diphosphonates 4-18 peptidase E Homo sapiens 93-95 10599049-11 1999 In conclusion, our study supports the contention that the antiresorptive effect of bisphosphonates may be due in part to a decrease in IL-6 production by osteoblasts. Diphosphonates 83-98 interleukin 6 Homo sapiens 135-139 10443797-0 1999 Amorphous calcium phosphate-mediated binding of matrix metalloproteinase-9 to fibrin is inhibited by pyrophosphate and bisphosphonate. Diphosphonates 119-133 matrix metallopeptidase 9 Homo sapiens 48-74 10425535-0 1999 The development of bone changes induced in rats by recombinant human granulocyte colony-stimulating factor is suppressed by bisphosphonate. Diphosphonates 124-138 colony stimulating factor 3 Homo sapiens 69-106 9761247-11 1998 The Tandem-MP Ostase bone ALP assay demonstrated increased concentrations of serum bone ALP in conditions where bone metabolism is increased and showed a rapid, temporal decrease in serum bone ALP in Paget disease patients on bisphosphonate therapy. Diphosphonates 226-240 ATHS Homo sapiens 26-29 10037008-2 1998 A class of anti-resorptive drugs known as bisphosphonates have been in use to treat osteoclast-mediated bone diseases for the past 3 decades, and are currently proving effective in the treatment of the bone disease associated with multiple myeloma. Diphosphonates 42-57 EH domain containing 3 Homo sapiens 126-132 9895279-3 1999 To explore the possibility of constructing photoactivatable probes from bisphosphonates to label the active site of V-PPase we analysed the effects of different analogues on the hydrolytic and proton pumping activity of the enzyme. Diphosphonates 72-87 inorganic pyrophosphatase 1 Homo sapiens 118-123 9895279-9 1999 An analogue with a ring attached via a four-carbon chain, which included an amide linkage and a hydroxy group on the alpha-carbon atom, inhibited competitively (Ki=62.0 microM), suggesting that it may be possible to design bisphosphonate inhibitors which contain a photoactivatable azido group for photoaffinity labelling of V-PPase active site. Diphosphonates 223-237 inorganic pyrophosphatase 1 Homo sapiens 327-332 10692979-4 1999 The results show that the response to antiresorptive bisphosphonate therapy in combination with calcium supplementation is modified by VDR genotype. Diphosphonates 53-67 vitamin D receptor Homo sapiens 135-138 9817938-4 1998 The size of the peaks corresponding to N-terminal OC fragments in Paget"s serum decreased 3 months after bisphosphonate treatment. Diphosphonates 105-119 bone gamma-carboxyglutamate protein Homo sapiens 50-52 9922036-8 1998 Interestingly, some studies have reported an improved survival in subsets of MM patients receiving BP and this is in agreement with recent evidence of possible direct anti-neoplastic activities of these drugs mediated through reduction of IL-6 production and stimulation of neoplastic cell apoptosis. Diphosphonates 99-101 interleukin 6 Homo sapiens 239-243 9761247-11 1998 The Tandem-MP Ostase bone ALP assay demonstrated increased concentrations of serum bone ALP in conditions where bone metabolism is increased and showed a rapid, temporal decrease in serum bone ALP in Paget disease patients on bisphosphonate therapy. Diphosphonates 226-240 ATHS Homo sapiens 88-91 9761247-11 1998 The Tandem-MP Ostase bone ALP assay demonstrated increased concentrations of serum bone ALP in conditions where bone metabolism is increased and showed a rapid, temporal decrease in serum bone ALP in Paget disease patients on bisphosphonate therapy. Diphosphonates 226-240 ATHS Homo sapiens 88-91 9648471-3 1998 Among these markers, deoxypyridinoline, NTx, and CTx are utilized for short-term judgement of efficacy during the early phase of anti-resorptive treatment, such as bisphosphonate and hormone replacement therapy. Diphosphonates 164-178 cytochrome P450 family 27 subfamily A member 1 Homo sapiens 49-52 9714526-6 1998 The observation that cytokine and cytokine receptor levels were reduced extends the possible and potential beneficial actions of bisphosphonates in multiple myeloma. Diphosphonates 129-144 interleukin 18 receptor 1 Homo sapiens 34-51 9738924-3 1998 MGP mRNA expression was restored to the level of uncalcified control by inhibiting BVSMC calcification with bisphosphonates. Diphosphonates 108-123 matrix Gla protein Bos taurus 0-3 9679953-0 1998 Tissue inhibitor of metalloproteinase-2 protection of matrix metalloproteinase-2 from degradation by plasmin is reversed by divalent cation chelator EDTA and the bisphosphonate alendronate. Diphosphonates 162-176 TIMP metallopeptidase inhibitor 1 Homo sapiens 0-37 9679953-0 1998 Tissue inhibitor of metalloproteinase-2 protection of matrix metalloproteinase-2 from degradation by plasmin is reversed by divalent cation chelator EDTA and the bisphosphonate alendronate. Diphosphonates 162-176 matrix metallopeptidase 2 Homo sapiens 54-80 9679953-0 1998 Tissue inhibitor of metalloproteinase-2 protection of matrix metalloproteinase-2 from degradation by plasmin is reversed by divalent cation chelator EDTA and the bisphosphonate alendronate. Diphosphonates 162-176 plasminogen Homo sapiens 101-108 9626812-3 1998 A potent bisphosphonate compound, alendronate, inhibited MMP-2 secretion to block solubilization of collagen 1. Diphosphonates 9-23 matrix metallopeptidase 2 Homo sapiens 57-62 9597690-1 1998 TRK-530 is a novel synthetic bisphosphonate compound which exhibits inhibitory activity in the rat adjuvant arthritis (AA) model. Diphosphonates 29-43 neurotrophic receptor tyrosine kinase 1 Rattus norvegicus 0-3 9597691-1 1998 TRK-530 is a novel bisphosphonate derivative. Diphosphonates 19-33 neurotrophic receptor tyrosine kinase 1 Rattus norvegicus 0-3 9284739-10 1997 The percent change from baseline obtained with tDPD, NTx, or CTx during bisphosphonate treatment were significantly different (P < 0.05), but this difference disappeared when the variability in the calcium carbonate group was taken into account. Diphosphonates 72-86 cytochrome P450 family 27 subfamily A member 1 Homo sapiens 61-64 9351880-16 1997 In vitro, an increase in TNF alpha and a mild increase in IL-6 was seen with all bisphosphonates, with the greatest effects seen with the highest concentration of both pamidronate and zoledronate. Diphosphonates 81-96 tumor necrosis factor Homo sapiens 25-34 9351880-16 1997 In vitro, an increase in TNF alpha and a mild increase in IL-6 was seen with all bisphosphonates, with the greatest effects seen with the highest concentration of both pamidronate and zoledronate. Diphosphonates 81-96 interleukin 6 Homo sapiens 58-62 9339740-0 1997 Alterations in the cardiopulmonary effects and pharmacokinetics of a bisphosphonate drug by a cytochrome P-450 inhibitor in conscious rats. Diphosphonates 69-83 cytochrome P450, family 2, subfamily g, polypeptide 1 Rattus norvegicus 94-110 9504956-0 1998 Bisphosphonate maintains parathyroid hormone (1-34)-induced cortical bone mass and mechanical strength in old rats. Diphosphonates 0-14 parathyroid hormone Rattus norvegicus 25-44 9563797-3 1998 The role of IL-6 in hypercalcemia and bone resorption would suggest that bisphosphonates or dexamethasone could be useful as adjuvant therapy for IL-6 dependent bone metastases which fail to respond to interferon alpha (IFN) alpha 2a and all trans retinoic acid (ATRA). Diphosphonates 73-88 interleukin 6 Homo sapiens 12-16 9563797-3 1998 The role of IL-6 in hypercalcemia and bone resorption would suggest that bisphosphonates or dexamethasone could be useful as adjuvant therapy for IL-6 dependent bone metastases which fail to respond to interferon alpha (IFN) alpha 2a and all trans retinoic acid (ATRA). Diphosphonates 73-88 interleukin 6 Homo sapiens 146-150 9564559-0 1998 Modification of serum apolipoprotein A-I, apolipoprotein B and lipoprotein(a) levels after bisphosphonates-induced acute phase response. Diphosphonates 91-106 apolipoprotein A1 Homo sapiens 22-40 9564559-0 1998 Modification of serum apolipoprotein A-I, apolipoprotein B and lipoprotein(a) levels after bisphosphonates-induced acute phase response. Diphosphonates 91-106 lipoprotein(a) Homo sapiens 63-77 9564559-3 1998 The aim of the present study was to investigate whether bisphosphonates, an effectual drug in the treatment of malignant hypercalcemia and Paget"s disease of bone, known to induce a concomitant acute phase, may have a significant influence on Lp(a) concentrations. Diphosphonates 56-71 lipoprotein(a) Homo sapiens 243-248 9564559-11 1998 Besides, we observed a slight but significant decrease of apo A-I and apo B after administration of bisphosphonates. Diphosphonates 100-115 apolipoprotein A1 Homo sapiens 58-75 9532611-1 1998 TRK-530, a newly synthesized bisphosphonate, was assessed for its effects on the accumulation of superoxide anions derived from human formyl-methionyl-leucyl-phenylalanine-stimulated polymorphonuclear leukocytes (PMN), and for its effects on bone resorption using a pit formation assay. Diphosphonates 29-43 neurotrophic receptor tyrosine kinase 1 Homo sapiens 0-3 9443074-0 1998 Structurally different bisphosphonates exert opposing effects on alkaline phosphatase and mineralization in marrow osteoprogenitors. Diphosphonates 23-38 alkaline phosphatase, placental Homo sapiens 65-85 9443074-7 1998 We found that the two different BPs have opposing effects on specific alkaline phosphatase (ALP) activity, on stromal-cell proliferation, and on cell-mediated mineralization. Diphosphonates 32-35 alkaline phosphatase, placental Homo sapiens 70-90 9443074-7 1998 We found that the two different BPs have opposing effects on specific alkaline phosphatase (ALP) activity, on stromal-cell proliferation, and on cell-mediated mineralization. Diphosphonates 32-35 alkaline phosphatase, placental Homo sapiens 92-95 9506876-0 1998 Bisphosphonates inhibit IL-6 production by human osteoblast-like cells. Diphosphonates 0-15 interleukin 6 Homo sapiens 24-28 9399997-11 1997 Among the seven diphosphonates tested, only etidronate and clodronate have a moderate affinity to the sulfate transporter, whereas the aminodiphosphonates have no (or low) affinity to any of the contraluminal anion transporters. Diphosphonates 16-30 solute carrier family 26 member 2 Homo sapiens 102-121 9401721-1 1997 TRK-530 is a newly synthesized diphosphonate derivative. Diphosphonates 31-44 neurotrophic tyrosine kinase, receptor, type 1 Mus musculus 0-3 9294486-10 1997 Pure human neutrophil collagenase (MMP-8) and the MMP-8 present in PISF and in the GCF of both loosening implants and periodontitis-affected teeth were efficiently inhibited in vitro by clodronate (50% inhibition [IC50] was achieved by 150 microM of clodronate), an osteoactive, antiresorptive bisphosphonate. Diphosphonates 294-308 matrix metallopeptidase 8 Homo sapiens 11-33 9294486-10 1997 Pure human neutrophil collagenase (MMP-8) and the MMP-8 present in PISF and in the GCF of both loosening implants and periodontitis-affected teeth were efficiently inhibited in vitro by clodronate (50% inhibition [IC50] was achieved by 150 microM of clodronate), an osteoactive, antiresorptive bisphosphonate. Diphosphonates 294-308 matrix metallopeptidase 8 Homo sapiens 35-40 9294486-10 1997 Pure human neutrophil collagenase (MMP-8) and the MMP-8 present in PISF and in the GCF of both loosening implants and periodontitis-affected teeth were efficiently inhibited in vitro by clodronate (50% inhibition [IC50] was achieved by 150 microM of clodronate), an osteoactive, antiresorptive bisphosphonate. Diphosphonates 294-308 matrix metallopeptidase 8 Homo sapiens 50-55 9193879-6 1997 The induction of CYP3A enzymes by the bisphosphonate SR-12813 suggests the existence of a new class of compounds with CYP3A inducing properties. Diphosphonates 38-52 cytochrome P450, family 3, subfamily a, polypeptide 62 Rattus norvegicus 17-22 9192515-1 1997 Interstitial collagenase present in human jaw cyst extract and purified human fibroblast-type collagenase (MMP-1) were both efficiently inhibited in vitro by clodronate, an osteoactive, antiresorptive bisphosphonate. Diphosphonates 201-215 matrix metallopeptidase 1 Homo sapiens 0-24 9192515-1 1997 Interstitial collagenase present in human jaw cyst extract and purified human fibroblast-type collagenase (MMP-1) were both efficiently inhibited in vitro by clodronate, an osteoactive, antiresorptive bisphosphonate. Diphosphonates 201-215 matrix metallopeptidase 1 Homo sapiens 107-112 9193879-6 1997 The induction of CYP3A enzymes by the bisphosphonate SR-12813 suggests the existence of a new class of compounds with CYP3A inducing properties. Diphosphonates 38-52 cytochrome P450, family 3, subfamily a, polypeptide 62 Rattus norvegicus 118-123 8837239-7 1996 The bone bisphosphonate clearance (BBC) at steady state was 26.0 ml min-1, a value which was significantly higher than that at infinity (16.5 ml min-1, p < 0.01). Diphosphonates 9-23 CD59 molecule (CD59 blood group) Homo sapiens 68-73 9135506-3 1997 Since the efficacy of IL-2 cancer immunotherapy, in part, depends on endogenous cytokine secretion, bisphosphonates could be effective in modulating IL-2 activity. Diphosphonates 100-115 interleukin 2 Homo sapiens 22-26 9135506-3 1997 Since the efficacy of IL-2 cancer immunotherapy, in part, depends on endogenous cytokine secretion, bisphosphonates could be effective in modulating IL-2 activity. Diphosphonates 100-115 interleukin 2 Homo sapiens 149-153 9135506-5 1997 On this basis, a pilot study was performed to evaluate the in vivo effects of the bisphosphonate, pamidronate, on blood levels of IL-6. Diphosphonates 82-96 interleukin 6 Homo sapiens 130-134 9135506-9 1997 This preliminary study shows that pamidronate infusion induces a rapid but transient decline in IL-6 blood concentrations, and suggests a possible use of bisphosphonates to modulate the efficacy of IL-2 cancer immunotherapy. Diphosphonates 154-169 interleukin 2 Homo sapiens 198-202 9051721-2 1997 These bisphosphonates had essentially similar effects on growth and the osteoblastic functions of the cells, i.e., they had no inhibitory effects on cell growth except at higher concentrations, they increased ALP activity, and inhibited PGE2 production. Diphosphonates 6-21 alkaline phosphatase, placental Homo sapiens 209-212 9085241-1 1997 Periodontal-like tissues and, in particular, alveolar bone- and root cementum-like material can theoretically be modulated by release of biochemical agents such as bisphosphonate (PCP), growth hormone (GH) and alkaline phosphatase (ALP) from the implant surface. Diphosphonates 164-178 alkaline phosphatase, placental Homo sapiens 232-235 8849398-13 1996 administration of bisphosphonates, the decrease of BALP was more marked than that of total ALP (median: -54% versus -41%; P < 0.05). Diphosphonates 18-33 ATHS Homo sapiens 52-55 8784085-13 1996 In a subgroup of 15 patients with metastatic BC, iv bisphosphonate treatment resulted in a rapid reduction of serum BSP levels to 40% of the baseline values within 4 days of treatment. Diphosphonates 52-66 integrin binding sialoprotein Homo sapiens 116-119 8782156-0 1996 Effects of bisphosphonates on interleukin 1, tumor necrosis factor alpha, and beta 2 microglobulin in rheumatoid arthritis. Diphosphonates 11-26 beta-2-microglobulin Homo sapiens 78-98 7586601-13 1995 CONCLUSIONS: This study shows that the addition of a bisphosphonate to GH replacement therapy in GHD adults counteracts the GH (or IGF-I) induced increase in renal phosphate reabsorption. Diphosphonates 53-67 insulin like growth factor 1 Homo sapiens 131-136 8610169-7 1996 ALN and another bisphosphonate, etidronate, also inhibited the activities of other bacterially expressed PTPs such as PTPsigma and CD45 (also called leukocyte common antigen). Diphosphonates 16-30 protein tyrosine phosphatase, receptor type, C Mus musculus 131-135 8610169-7 1996 ALN and another bisphosphonate, etidronate, also inhibited the activities of other bacterially expressed PTPs such as PTPsigma and CD45 (also called leukocyte common antigen). Diphosphonates 16-30 protein tyrosine phosphatase, receptor type, C Mus musculus 149-173 8730126-4 1996 RESULTS: Bisphosphonates inhibited ALP Pase activity more than ALP PPiase activity at the same concentrations. Diphosphonates 9-24 alkaline phosphatase, placental Homo sapiens 35-38 8730126-9 1996 Bisphosphonates at high concentrations inhibited ALP CPPD crystal dissolution. Diphosphonates 0-15 alkaline phosphatase, placental Homo sapiens 49-52 8730126-10 1996 The strong inhibitory effects of bisphosphonates on ALP CPPD crystal dissolution compared to those on ALP PPiase activity suggest that bisphosphonates inhibit crystal dissolution by their affinity for the CPPD crystal surface. Diphosphonates 33-48 alkaline phosphatase, placental Homo sapiens 52-55 8730126-10 1996 The strong inhibitory effects of bisphosphonates on ALP CPPD crystal dissolution compared to those on ALP PPiase activity suggest that bisphosphonates inhibit crystal dissolution by their affinity for the CPPD crystal surface. Diphosphonates 135-150 alkaline phosphatase, placental Homo sapiens 52-55 8730126-10 1996 The strong inhibitory effects of bisphosphonates on ALP CPPD crystal dissolution compared to those on ALP PPiase activity suggest that bisphosphonates inhibit crystal dissolution by their affinity for the CPPD crystal surface. Diphosphonates 135-150 alkaline phosphatase, placental Homo sapiens 102-105 8730126-10 1996 The strong inhibitory effects of bisphosphonates on ALP CPPD crystal dissolution compared to those on ALP PPiase activity suggest that bisphosphonates inhibit crystal dissolution by their affinity for the CPPD crystal surface. Diphosphonates 135-150 FKBP prolyl isomerase 1B Homo sapiens 106-112 8992885-6 1996 The bacterial-expressed hPTP sigma exhibits PTPase activity that was inhibited by orthovanadate (IC50 = 0.02 microM) and by two bisphosphonates used for the treatment of bone diseases, alendronate (ALN) (IC50 = 0.5 microM) and etidronate (IC50 = 0.2 microM). Diphosphonates 128-143 protein tyrosine phosphatase receptor type U Homo sapiens 24-28 8992885-8 1996 These findings show tissue-specific alternative splicing of PTP sigma and suggest that PTPs are putative targets of bisphosphonate action. Diphosphonates 116-130 protein tyrosine phosphatase receptor type U Homo sapiens 60-63 8730126-2 1996 We studied the effects of enzyme inhibitors such as bisphosphonates, orthovanadate, calcium, cadmium, and ascorbic acid on PPiase activity of ALP as well as on phosphate ester hydrolysis (Pase) activity and compared these effects to those on CPPD crystal dissolution. Diphosphonates 52-67 FKBP prolyl isomerase 1B Homo sapiens 123-129 8730126-2 1996 We studied the effects of enzyme inhibitors such as bisphosphonates, orthovanadate, calcium, cadmium, and ascorbic acid on PPiase activity of ALP as well as on phosphate ester hydrolysis (Pase) activity and compared these effects to those on CPPD crystal dissolution. Diphosphonates 52-67 alkaline phosphatase, placental Homo sapiens 142-145 8833207-0 1996 Interleukin-6 and tumor necrosis factor alpha levels after bisphosphonates treatment in vitro and in patients with malignancy. Diphosphonates 59-74 interleukin 6 Homo sapiens 0-45 8573423-7 1995 Since many results have been published showing a dramatic effect of several bisphosphonates in Paget"s disease of bone, nasal and rectal calcitonin are no longer considered as the treatments of choice in this condition. Diphosphonates 76-91 calcitonin related polypeptide alpha Homo sapiens 137-147 7572320-0 1995 Interleukin-6 and the acute phase response during treatment of patients with Paget"s disease with the nitrogen-containing bisphosphonate dimethylaminohydroxypropylidene bisphosphonate. Diphosphonates 122-136 interleukin 6 Homo sapiens 0-13 7669436-0 1995 The anabolic effect of human PTH (1-34) on bone formation is blunted when bone resorption is inhibited by the bisphosphonate tiludronate--is activated resorption a prerequisite for the in vivo effect of PTH on formation in a remodeling system? Diphosphonates 110-124 parathyroid hormone Homo sapiens 29-32 7669436-0 1995 The anabolic effect of human PTH (1-34) on bone formation is blunted when bone resorption is inhibited by the bisphosphonate tiludronate--is activated resorption a prerequisite for the in vivo effect of PTH on formation in a remodeling system? Diphosphonates 110-124 parathyroid hormone Homo sapiens 203-206 7629799-8 1995 In contrast, all three corresponding bisphosphonates I are potent squalene synthase inhibitors. Diphosphonates 37-52 farnesyl diphosphate farnesyl transferase 1 Rattus norvegicus 66-83 8018531-1 1994 Plasma parathyroid hormone related-protein (PTHrP) may inhibit the calcium-lowering effect of bisphosphonate therapy. Diphosphonates 94-108 parathyroid hormone like hormone Homo sapiens 7-42 7785896-7 1995 However, OPN mRNA is down-regulated by bisphosphonates, which abrogate bone resorption. Diphosphonates 39-54 secreted phosphoprotein 1 Rattus norvegicus 9-12 7599454-2 1995 Administration of suppressive doses of the bisphosphonate to patients with excessive osteoclastic resorption is followed by transient decreases in serum calcium and increases in parathyroid hormone (PTH) concentrations. Diphosphonates 43-57 parathyroid hormone Homo sapiens 178-197 8528347-11 1994 In addition, some bisphosphonates would certainly promote PTH-independent production of 1,25-(OH)2D2. Diphosphonates 18-33 parathyroid hormone Homo sapiens 58-61 7667201-0 1995 Effect of liposomal and free bisphosphonates on the IL-1 beta, IL-6 and TNF alpha secretion from RAW 264 cells in vitro. Diphosphonates 29-44 interleukin 1 beta Mus musculus 52-61 7667201-0 1995 Effect of liposomal and free bisphosphonates on the IL-1 beta, IL-6 and TNF alpha secretion from RAW 264 cells in vitro. Diphosphonates 29-44 tumor necrosis factor Mus musculus 72-81 7851410-5 1995 Bisphosphonates, such as disodium-1-hydroxy-1-aminopropylidine-1,1-diphosphonate (APD) and ethane-1-hydroxy-1,1-diphosphonate (HEBP), at increased concentrations, inhibited ALP amino acid phosphatase activity. Diphosphonates 0-15 alkaline phosphatase, placental Homo sapiens 173-176 8018531-1 1994 Plasma parathyroid hormone related-protein (PTHrP) may inhibit the calcium-lowering effect of bisphosphonate therapy. Diphosphonates 94-108 parathyroid hormone like hormone Homo sapiens 44-49 8018531-6 1994 Patients who responded to bisphosphonate therapy by becoming normocalcaemic had significantly lower basal plasma PTHrP levels, mean 4.06 vs 8.2 pmol l-1 (P < 0.04). Diphosphonates 26-40 parathyroid hormone like hormone Homo sapiens 113-118 8071580-2 1994 Bisphosphonates such as disodium-1-hydroxy-1-aminopropylidine-1,1-diphosphonate (APD) and ethane-1-hydroxy-1,1"-diphosphonate (HEDP) inhibited ALP phosphate ester hydrolysis activity more than PPase activity at the same concentrations. Diphosphonates 0-15 alkaline phosphatase, placental Homo sapiens 143-146 8035344-1 1994 In order to enhance the entry into cells of L-690,330, a bisphosphonate inhibitor of inositol monophosphatase (IMPase; a key, enzyme in the phosphatidylinositol (Pl) cell signaling pathway), the tetrapivaloyloxymethyl ester prodrug, L-690,488 [tetrapivaloyloxymethyl 1-(4-hydroxyphenoxy)ethane-1,1-bisphosphonate], was synthesized. Diphosphonates 57-71 inositol monophosphatase 1 Cricetulus griseus 85-109 8027221-1 1994 The effect of a new third generation bisphosphonate, YM175 (cycloheptylamino-methylene bisphosphonate), on serum calcium (Ca) and intact PTH levels was examined in 79 malignancy-associated hypercalcemia patients with serum Ca levels higher than 2.75 mmol/L. Diphosphonates 37-51 parathyroid hormone Homo sapiens 137-140 8071580-2 1994 Bisphosphonates such as disodium-1-hydroxy-1-aminopropylidine-1,1-diphosphonate (APD) and ethane-1-hydroxy-1,1"-diphosphonate (HEDP) inhibited ALP phosphate ester hydrolysis activity more than PPase activity at the same concentrations. Diphosphonates 0-15 inorganic pyrophosphatase 1 Homo sapiens 193-198 8175989-11 1994 We conclude that in hypercalcemia of malignancy raised serum levels of PTHrP indicate a reduced hypocalcemic response to bisphosphonates, a more advanced tumor state and, therefore, an extremely poor prognosis. Diphosphonates 121-136 parathyroid hormone like hormone Homo sapiens 71-76 8287315-0 1993 Decrease of serum calcium concentration and lost influence of calcium on parathyroid hormone release in a patient with primary hyperparathyroidism after treatment with diphosphonates. Diphosphonates 168-182 parathyroid hormone Homo sapiens 73-92 8156530-0 1994 Significance of plasma PTH-rp in patients with hypercalcemia of malignancy treated with bisphosphonate. Diphosphonates 88-102 parathyroid hormone like hormone Homo sapiens 23-29 8156530-14 1994 CONCLUSIONS: The plasma PTH-rp levels may help to predict the calcium-lowering effect of bisphosphonate and give an indication of the prognosis in patients with HM. Diphosphonates 89-103 parathyroid hormone like hormone Homo sapiens 24-30 8030440-2 1994 We conducted this study to examine the effects of treatment with a bisphosphonate on serum PTHrP. Diphosphonates 67-81 parathyroid hormone like hormone Homo sapiens 91-96 7858955-6 1994 All three bisphosphonates encapsulated in liposomes effectively inhibited the growth of RAW 264 and CV1-P cells, while free drugs were 20-1000 times less potent growth inhibitors. Diphosphonates 10-25 endogenous ecotropic MuLV 1 Mus musculus 100-103 8518293-1 1993 Several bisphosphonates were examined as inhibitors of yeast GPD (glyceraldehyde-3-phosphate dehydrogenase, EC 1.2.1.12) and PGK (phosphoglycerate kinase, EC 2.7.2.3). Diphosphonates 8-23 phosphoglycerate kinase Saccharomyces cerevisiae S288C 125-128 8104954-8 1993 In patients with Paget"s disease, B-ALP was highly correlated with T-ALP (r2 = 0.94; P < 0.001), and the decrease in its serum level was larger than that in T-ALP after treatment with the bisphosphonate pamidronate (-58% vs. -43%; P < 0.03). Diphosphonates 191-205 ATHS Homo sapiens 36-39 8518293-1 1993 Several bisphosphonates were examined as inhibitors of yeast GPD (glyceraldehyde-3-phosphate dehydrogenase, EC 1.2.1.12) and PGK (phosphoglycerate kinase, EC 2.7.2.3). Diphosphonates 8-23 phosphoglycerate kinase Saccharomyces cerevisiae S288C 130-153 8380439-0 1993 In vitro and in vivo inhibition of inositol monophosphatase by the bisphosphonate L-690,330. Diphosphonates 67-81 inositol monophosphatase 1 Cricetulus griseus 35-59 8328312-0 1993 Circulating PTHrP concentrations in tumor-induced hypercalcemia: influence on the response to bisphosphonate and changes after therapy. Diphosphonates 94-108 parathyroid hormone like hormone Homo sapiens 12-17 8328312-1 1993 We studied the influence of circulating parathyroid hormone-related protein (PTHrP) concentrations on the response of hypercalcemic cancer patients to bisphosphonate therapy. Diphosphonates 151-165 parathyroid hormone like hormone Homo sapiens 40-75 8328312-1 1993 We studied the influence of circulating parathyroid hormone-related protein (PTHrP) concentrations on the response of hypercalcemic cancer patients to bisphosphonate therapy. Diphosphonates 151-165 parathyroid hormone like hormone Homo sapiens 77-82 8380439-1 1993 We have previously described the synthesis of bisphosphonate-containing inhibitors of inositol monophosphatase. Diphosphonates 46-60 inositol monophosphatase 1 Cricetulus griseus 86-110 8164618-5 1993 These results suggest that TRAP could be a useful marker to evaluate the changes of bone resorption induced by bisphosphonates in the rat together with the classical marker OH-Prol. Diphosphonates 111-126 acid phosphatase 5, tartrate resistant Rattus norvegicus 27-31 8428711-2 1993 In 10 patients with hypercalcemia of malignancy the levels of the midregional fragment of PTHrP in serum were determined by radioimmunoassay over 7 days during a calcium-lowering treatment with a single dose of the bisphosphonate BM 21.0955. Diphosphonates 215-229 parathyroid hormone like hormone Homo sapiens 90-95 8273598-1 1993 Six diphosphonates were examined for their ability to alter proliferative responses of mouse bone marrow cells to recombinant human M-CSF and recombinant murine GM-CSF. Diphosphonates 4-18 colony stimulating factor 1 Homo sapiens 132-137 8273598-1 1993 Six diphosphonates were examined for their ability to alter proliferative responses of mouse bone marrow cells to recombinant human M-CSF and recombinant murine GM-CSF. Diphosphonates 4-18 colony stimulating factor 2 (granulocyte-macrophage) Mus musculus 161-167 1292341-0 1992 Bisphosphonate kinetics in patients undergoing continuous ambulatory peritoneal dialysis: relations to dynamic bone histomorphometry, osteocalcin and parathyroid hormone. Diphosphonates 0-14 bone gamma-carboxyglutamate protein Homo sapiens 134-145 1464749-0 1992 Bisphosphonates used for the treatment of bone disorders inhibit squalene synthase and cholesterol biosynthesis. Diphosphonates 0-15 farnesyl diphosphate farnesyl transferase 1 Rattus norvegicus 65-82 1609087-0 1992 Epi- and metaphyseal changes in children caused by administration of bisphosphonates. Diphosphonates 69-84 tissue factor pathway inhibitor Homo sapiens 0-3 1292341-0 1992 Bisphosphonate kinetics in patients undergoing continuous ambulatory peritoneal dialysis: relations to dynamic bone histomorphometry, osteocalcin and parathyroid hormone. Diphosphonates 0-14 parathyroid hormone Homo sapiens 150-169 1839590-6 1991 These studies describe a new phenomenon, that low doses of nitrogen-containing bisphosphonates can act synergistically with PTH and enhance osteoclastic resorption. Diphosphonates 79-94 parathyroid hormone Mus musculus 124-127 1338636-4 1992 The PTHrP-stimulated bone resorption can be totally inhibited by bisphosphonate therapy. Diphosphonates 65-79 parathyroid hormone like hormone Homo sapiens 4-9 1839590-0 1991 Modulation of PTH-stimulated osteoclastic resorption by bisphosphonates in fetal mouse bone explants. Diphosphonates 56-71 parathyroid hormone Mus musculus 14-17 1835718-0 1991 Effects of vitamin D metabolites and bisphosphonates on fibronectin release from monocyte-derived macrophages. Diphosphonates 37-52 fibronectin 1 Homo sapiens 56-67 1835397-6 1991 This type of therapeutic response can be reproduced experimentally in bisphosphonate-treated animals receiving a constant infusion of parathyroid hormone-related peptide, a peptide isolated from various tumour types including lung, kidney, breast and neuroendocrine tumour of the pancreas. Diphosphonates 70-84 parathyroid hormone like hormone Homo sapiens 134-169 2158662-7 1990 The PTHrP-induced increase in bone Ca resorption is completely inhibitable by diphosphonate therapy. Diphosphonates 78-91 parathyroid hormone-like hormone Rattus norvegicus 4-9 2137362-6 1990 This type of therapeutic response can be experimentally reproduced in diphosphonate-treated animals receiving a constant infusion of parathyroid hormone-related peptide, a peptide isolated from lung, kidney and breast carcinomas. Diphosphonates 70-83 parathyroid hormone like hormone Homo sapiens 133-168 2158662-8 1990 Despite this efficacious antiosteolytic response the fall in calcemia is moderate since the marked effect of PTHrP on the renal transport of Ca is maintained under diphosphonate therapy. Diphosphonates 164-177 parathyroid hormone-like hormone Rattus norvegicus 109-114 33031053-4 2020 Herein, we report long-term follow-up of two cases with novel SERPINF1 mutations, who show great variation in their treatment response to bisphosphonates. Diphosphonates 138-153 serpin family F member 1 Homo sapiens 62-70 33820804-4 2021 The patient also continued to receive bisphosphonates during her preoperative and postoperative period, to improve bone stock and aid in relieving pain. Diphosphonates 38-53 activation induced cytidine deaminase Homo sapiens 130-133 34920168-1 2022 Bisphosphonates are effective in reducing hip and other fractures. Diphosphonates 0-15 hedgehog interacting protein Homo sapiens 42-45 22783728-3 2012 Bisphosphonates have low bioavailability (1-10%) and low absorption (for more recent bisphosphonates it does not exceed 1%) after oral application (class III of BCS). Diphosphonates 0-15 BCS1 homolog, ubiquinol-cytochrome c reductase complex chaperone Homo sapiens 161-164 25055746-14 2015 CONCLUSIONS: This study shows for the first time that mechanical loading alters the effects of bisphosphonates on viability, apoptosis rate, and OPG/RANKL system of HPdLF dependent on the applied strength. Diphosphonates 95-110 TNF receptor superfamily member 11b Homo sapiens 145-148 25055746-14 2015 CONCLUSIONS: This study shows for the first time that mechanical loading alters the effects of bisphosphonates on viability, apoptosis rate, and OPG/RANKL system of HPdLF dependent on the applied strength. Diphosphonates 95-110 TNF superfamily member 11 Homo sapiens 149-154 21702715-7 2011 Remarkable for their high bone mineral affinity, BPs are structural mimics of the dimethylallyl pyrophosphate substrate of FPPS, and constitute the major type of FPPS inhibitor currently used in the clinic for treatment of bone-related diseases. Diphosphonates 49-52 farnesyl diphosphate synthase Homo sapiens 123-127 21702715-7 2011 Remarkable for their high bone mineral affinity, BPs are structural mimics of the dimethylallyl pyrophosphate substrate of FPPS, and constitute the major type of FPPS inhibitor currently used in the clinic for treatment of bone-related diseases. Diphosphonates 49-52 farnesyl diphosphate synthase Homo sapiens 162-166 34896359-7 2022 The synthesis and biological evaluation of a large number of nitrogen-containing bisphosphonates in the 1980s and 1990s led to the key discovery that the antiresorptive effects of these more complex analogs on osteoclasts result mostly from their potency as inhibitors of the enzyme farnesyl diphosphate synthase (FDPS/FPPS). Diphosphonates 81-96 farnesyl diphosphate synthase Homo sapiens 283-312 34896359-7 2022 The synthesis and biological evaluation of a large number of nitrogen-containing bisphosphonates in the 1980s and 1990s led to the key discovery that the antiresorptive effects of these more complex analogs on osteoclasts result mostly from their potency as inhibitors of the enzyme farnesyl diphosphate synthase (FDPS/FPPS). Diphosphonates 81-96 farnesyl diphosphate synthase Homo sapiens 314-318 34896359-7 2022 The synthesis and biological evaluation of a large number of nitrogen-containing bisphosphonates in the 1980s and 1990s led to the key discovery that the antiresorptive effects of these more complex analogs on osteoclasts result mostly from their potency as inhibitors of the enzyme farnesyl diphosphate synthase (FDPS/FPPS). Diphosphonates 81-96 farnesyl diphosphate synthase Homo sapiens 319-323 34896359-9 2022 Since then, it has become even more clear that the overall pharmacological effects of individual bisphosphonates on bone depend upon two key properties: the affinity for bone mineral and inhibitory effects on biochemical targets within bone cells, in particular FDPS. Diphosphonates 97-112 farnesyl diphosphate synthase Homo sapiens 262-266 34585781-0 2022 Total Hip Bone Mineral Density as an Indicator of Fracture Risk in Bisphosphonate-Treated Patients in a Real-World Setting. Diphosphonates 67-81 hedgehog interacting protein Homo sapiens 6-9 34740282-1 2022 In genome-wide association studies, the CYP2C8 gene locus has been reported to be associated with bisphosphonate-related osteonecrosis of the jaw, a severe devastating side effect of antiresorptive bone treatment. Diphosphonates 98-112 cytochrome P450 family 2 subfamily C member 8 Homo sapiens 40-46 34740282-5 2022 Enhanced bisphosphonate-induced uncoupling of the CYP2C8 enzyme was detected in the variant allele (CYP2C8*3) with the result of increased H2O2 production and lowered substrate oxidation. Diphosphonates 9-23 cytochrome P450 family 2 subfamily C member 8 Homo sapiens 50-56 34970353-0 2022 VEGF mitigates bisphosphonate-induced apoptosis and differentiation inhibition of MC3T3-E1 cells. Diphosphonates 15-29 vascular endothelial growth factor A Mus musculus 0-4 34970353-1 2022 The present study aimed to investigate whether VEGF was involved in bisphosphonate (BP)-induced apoptosis and differentiation of osteoblasts. Diphosphonates 68-82 vascular endothelial growth factor A Mus musculus 47-51 34970353-1 2022 The present study aimed to investigate whether VEGF was involved in bisphosphonate (BP)-induced apoptosis and differentiation of osteoblasts. Diphosphonates 84-86 vascular endothelial growth factor A Mus musculus 47-51 34970353-12 2022 The present study demonstrated that VEGF could attenuate BP-induced apoptosis and differentiation of MC3T3 cells by regulating the NLRP3/caspase 1/GSDMD pathway. Diphosphonates 57-59 vascular endothelial growth factor A Mus musculus 36-40 34970353-12 2022 The present study demonstrated that VEGF could attenuate BP-induced apoptosis and differentiation of MC3T3 cells by regulating the NLRP3/caspase 1/GSDMD pathway. Diphosphonates 57-59 NLR family, pyrin domain containing 3 Mus musculus 131-136 34970353-12 2022 The present study demonstrated that VEGF could attenuate BP-induced apoptosis and differentiation of MC3T3 cells by regulating the NLRP3/caspase 1/GSDMD pathway. Diphosphonates 57-59 caspase 1 Mus musculus 137-146 34970353-12 2022 The present study demonstrated that VEGF could attenuate BP-induced apoptosis and differentiation of MC3T3 cells by regulating the NLRP3/caspase 1/GSDMD pathway. Diphosphonates 57-59 gasdermin D Mus musculus 147-152 34534710-8 2022 Cutoff points of 50.0% CTX-I decrease and 23.5% for osteocalcin decrease had the highest sensitivities and specificities for detecting BMD responders for bisphosphonate users, but cutoffs could not be found for SERM users. Diphosphonates 154-168 bone gamma-carboxyglutamate protein Homo sapiens 52-63 34934885-0 2021 A Paradigm Shift in Osteonecrosis Treatment with Bisphosphonates: A 20-Year Study. Diphosphonates 49-64 immunoglobulin kappa variable 1-27 Homo sapiens 66-70 34024253-10 2021 Altogether, PTHrP can inhibit nitrogen-containing BP-induced apoptosis of HPdLFs by activating MKP1 phosphatase. Diphosphonates 50-52 parathyroid hormone like hormone Homo sapiens 12-17 34024253-10 2021 Altogether, PTHrP can inhibit nitrogen-containing BP-induced apoptosis of HPdLFs by activating MKP1 phosphatase. Diphosphonates 50-52 dual specificity phosphatase 1 Homo sapiens 95-99 34024253-0 2021 Parathyroid hormone-related protein inhibits nitrogen-containing bisphosphonate-induced apoptosis of human periodontal ligament fibroblasts by activating MKP1 phosphatase. Diphosphonates 65-79 parathyroid hormone like hormone Homo sapiens 0-35 34390503-9 2021 FDFT1 encodes a membrane-associated enzyme which is implicated in the bisphosphonates pathway. Diphosphonates 70-85 farnesyl-diphosphate farnesyltransferase 1 Homo sapiens 0-5 34024253-0 2021 Parathyroid hormone-related protein inhibits nitrogen-containing bisphosphonate-induced apoptosis of human periodontal ligament fibroblasts by activating MKP1 phosphatase. Diphosphonates 65-79 dual specificity phosphatase 1 Homo sapiens 154-158 34024253-4 2021 Therefore, it is speculated that PTHrP can inhibit the apoptosis of HPdLFs caused by nitrogen-containing BP via regulating the expression levels of MKP1. Diphosphonates 105-107 parathyroid hormone like hormone Homo sapiens 33-38 34024253-4 2021 Therefore, it is speculated that PTHrP can inhibit the apoptosis of HPdLFs caused by nitrogen-containing BP via regulating the expression levels of MKP1. Diphosphonates 105-107 dual specificity phosphatase 1 Homo sapiens 148-152 34166796-5 2021 A missense mutation on the gene TNFRSF11B was identified in homozygosity, and the diagnosis of JPD was made.Treatment with bisphosphonates was initiated early and markedly improved lower limb bowing and pain. Diphosphonates 123-138 TNF receptor superfamily member 11b Homo sapiens 32-41 33757387-5 2021 Only the bisphosphonate containing compound RC2 bound stronger to PLN and TLN than to MMP-9 and MMP-14. Diphosphonates 9-23 matrix metallopeptidase 9 Homo sapiens 86-91 34347453-0 2021 Bisphosphonate-Conjugated Photo-Crosslinking Polyanionic Hyaluronic Acid Microbeads for Controlled BMP2 Delivery and Enhanced Bone Formation Efficacy. Diphosphonates 0-14 bone morphogenetic protein 2 Rattus norvegicus 99-103 34347277-8 2021 The expression levels of bone regeneration markers (RUNX2, OSX, and BMP-2) significantly increased in BP-treated rBM-derived cells, after co-culture with hUC-MSCs. Diphosphonates 102-104 RUNX family transcription factor 2 Homo sapiens 52-57 34347277-8 2021 The expression levels of bone regeneration markers (RUNX2, OSX, and BMP-2) significantly increased in BP-treated rBM-derived cells, after co-culture with hUC-MSCs. Diphosphonates 102-104 Sp7 transcription factor Homo sapiens 59-62 34347277-8 2021 The expression levels of bone regeneration markers (RUNX2, OSX, and BMP-2) significantly increased in BP-treated rBM-derived cells, after co-culture with hUC-MSCs. Diphosphonates 102-104 bone morphogenetic protein 2 Homo sapiens 68-73 34347277-9 2021 The BP-induced abnormal shift in RANKL/OPG expression ratio in rBM-derived cells was normalized by hUC-MSCs. Diphosphonates 4-6 TNF superfamily member 11 Homo sapiens 33-38 34347277-9 2021 The BP-induced abnormal shift in RANKL/OPG expression ratio in rBM-derived cells was normalized by hUC-MSCs. Diphosphonates 4-6 basic transcription factor 3 pseudogene 11 Homo sapiens 39-42 34347453-1 2021 In this study, we designed bisphosphonate-conjugated polyanionic hyaluronic acid (HA) microbeads (MBs) for the controlled delivery of bone morphogenetic protein 2 (BMP2). Diphosphonates 27-41 bone morphogenetic protein 2 Rattus norvegicus 134-162 34347453-1 2021 In this study, we designed bisphosphonate-conjugated polyanionic hyaluronic acid (HA) microbeads (MBs) for the controlled delivery of bone morphogenetic protein 2 (BMP2). Diphosphonates 27-41 bone morphogenetic protein 2 Rattus norvegicus 164-168 34335676-7 2021 Compared with the non-bisphosphonate treatment group, patients treated with bisphosphonates had higher lumbar spine BMD, fewer fractures, and lower levels of beta-CTX and osteocalcin. Diphosphonates 22-36 bone gamma-carboxyglutamate protein Homo sapiens 158-182 34360204-10 2021 Initial prostate-specific antigen level (PSA level) indicated if a patient would be treated with bisphosphonate or not (95% CI 45.51-96.14, p = 0.002). Diphosphonates 97-111 kallikrein related peptidase 3 Homo sapiens 8-33 34534754-3 2021 Bisphosphonates preserve bone mineral density at the hip but not at the knee, which is the anatomical site most prone to fracture in the SCI population. Diphosphonates 0-15 hedgehog interacting protein Homo sapiens 53-56 34075628-0 2021 Nitrogen-containing Bisphosphonates and Lipopolysaccharide Mutually Augment Inflammation via ATP- and IL-1beta-mediated Production of NETs. Diphosphonates 20-35 interleukin 1 alpha Homo sapiens 102-110 34335676-7 2021 Compared with the non-bisphosphonate treatment group, patients treated with bisphosphonates had higher lumbar spine BMD, fewer fractures, and lower levels of beta-CTX and osteocalcin. Diphosphonates 76-91 bone gamma-carboxyglutamate protein Homo sapiens 158-182 34299011-4 2021 Previous studies uncovered rare CYP1A1 mutations in osteoporosis patients who suffered AFF after long-term BP treatment. Diphosphonates 107-109 cytochrome P450 family 1 subfamily A member 1 Homo sapiens 32-38 34299011-10 2021 Moreover, all the BP treatments decreased CYP1A1 activity, although no specific interaction with CYP1A1 variants was found. Diphosphonates 18-20 cytochrome P450 family 1 subfamily A member 1 Homo sapiens 42-48 34299011-11 2021 Our results provide functional support to the hypothesis that an additive effect between CYP1A1 heterozygous mutations p.Arg98Trp and p.Arg136His, other rare mutations and long-term BP exposure might generate susceptibility to AFF. Diphosphonates 182-184 cytochrome P450 family 1 subfamily A member 1 Homo sapiens 89-95 34275224-1 2021 Objective: To study the relationship between zoledronic acid (ZOL) and vascular endothelial growth factor (VEGF) conformation so as to reveal the mechanism of bisphosphonates inhibiting angiogenesis. Diphosphonates 159-174 vascular endothelial growth factor A Homo sapiens 71-105 34275224-1 2021 Objective: To study the relationship between zoledronic acid (ZOL) and vascular endothelial growth factor (VEGF) conformation so as to reveal the mechanism of bisphosphonates inhibiting angiogenesis. Diphosphonates 159-174 vascular endothelial growth factor A Homo sapiens 107-111 34194443-7 2021 The association between ACPA and BMD loss was independent of other variables including age, gender, disease activity, cumulative dose of glucocorticoids and duration of therapy with bisphosphonates at the LS but not the FN. Diphosphonates 182-197 proteinase 3 Homo sapiens 24-28 34279472-7 2021 Significant suppression of the RANKL/OPG ratio and Kcnn4 expression among the retrieved bones of IV BP group patients was also noted. Diphosphonates 100-102 TNF superfamily member 11 Homo sapiens 31-36 34279472-7 2021 Significant suppression of the RANKL/OPG ratio and Kcnn4 expression among the retrieved bones of IV BP group patients was also noted. Diphosphonates 100-102 TNF receptor superfamily member 11b Homo sapiens 37-40 34279472-7 2021 Significant suppression of the RANKL/OPG ratio and Kcnn4 expression among the retrieved bones of IV BP group patients was also noted. Diphosphonates 100-102 potassium calcium-activated channel subfamily N member 4 Homo sapiens 51-56 34137822-3 2021 Zoledronate is a nitrogen containing bisphosphonate, which inhibits the farnesyl pyrophosphate synthase (FPPS) enzyme, central to the mevalonate pathway. Diphosphonates 37-51 Farnesyl pyrophosphate synthase Drosophila melanogaster 72-103 34137822-3 2021 Zoledronate is a nitrogen containing bisphosphonate, which inhibits the farnesyl pyrophosphate synthase (FPPS) enzyme, central to the mevalonate pathway. Diphosphonates 37-51 Farnesyl pyrophosphate synthase Drosophila melanogaster 105-109 34476054-0 2021 Dissecting the activation of insulin degrading enzyme by inositol pyrophosphates and their bisphosphonate analogs. Diphosphonates 91-105 insulin Homo sapiens 29-36 34277895-9 2021 Conclusions: Patients with pathogenic variants in the C-propeptide region of COL1A1/A2 and BMP1 appear to have a high bone mass phenotype with increased sensitivity to bisphosphonate therapy. Diphosphonates 168-182 collagen type I alpha 1 chain Homo sapiens 77-83 34277895-9 2021 Conclusions: Patients with pathogenic variants in the C-propeptide region of COL1A1/A2 and BMP1 appear to have a high bone mass phenotype with increased sensitivity to bisphosphonate therapy. Diphosphonates 168-182 bone morphogenetic protein 1 Homo sapiens 91-95 34081758-0 2021 (Predictive relevance of KRAS mutational status in bone metastatic lung adenocarcinoma treated with bisphosphonate therapy). Diphosphonates 100-114 KRAS proto-oncogene, GTPase Homo sapiens 25-29 34200782-0 2021 Machine Learning Approaches for Predicting Bisphosphonate-Related Osteonecrosis in Women with Osteoporosis Using VEGFA Gene Polymorphisms. Diphosphonates 43-57 vascular endothelial growth factor A Homo sapiens 113-118 34200782-1 2021 OBJECTIVE: This nested case-control study aimed to investigate the effects of VEGFA polymorphisms on the development of bisphosphonate-related osteonecrosis of the jaw (BRONJ) in women with osteoporosis. Diphosphonates 120-134 vascular endothelial growth factor A Homo sapiens 78-83 34081758-2 2021 Therefore, our aim was to investigate the effects of KRAS mutational status on overall survival (OS) in these patients according to bisphosphonate therapy (BTx) and radiation therapy (RTx). Diphosphonates 132-146 KRAS proto-oncogene, GTPase Homo sapiens 53-57 33991130-4 2021 We first synthesized 22 different nitrogen-containing bisphosphonate molecules that were designed to inhibit squalene synthase. Diphosphonates 54-68 farnesyl-diphosphate farnesyltransferase 1 Homo sapiens 109-126 33991130-5 2021 Squalene synthase inhibition was quantified using a cell-free enzyme assay, and validated by computer modeling of bisphosphonate molecules binding to squalene synthase. Diphosphonates 114-128 farnesyl-diphosphate farnesyltransferase 1 Homo sapiens 0-17 33991130-5 2021 Squalene synthase inhibition was quantified using a cell-free enzyme assay, and validated by computer modeling of bisphosphonate molecules binding to squalene synthase. Diphosphonates 114-128 farnesyl-diphosphate farnesyltransferase 1 Homo sapiens 150-167 33991130-6 2021 The bisphosphonates were then screened for their ability to protect HeLa cells against the damage caused by the cholesterol-dependent cytolysin, pyolysin. Diphosphonates 4-19 perforin 1 Homo sapiens 134-143 33991130-9 2021 The bisphosphonate also protected cells against another cholesterol-dependent cytolysin, streptolysin O, and protected lung epithelial cells and primary dermal fibroblasts against cytolysis. Diphosphonates 4-18 perforin 1 Homo sapiens 78-87 33991130-10 2021 Our findings imply that treatment with bisphosphonates that inhibit squalene synthase might help protect tissues against pathogenic bacteria that secrete cholesterol-dependent cytolysins. Diphosphonates 39-54 farnesyl-diphosphate farnesyltransferase 1 Homo sapiens 68-85 35600875-3 2022 Nitrogen-containing bisphosphonates suppress osteoclastic resorption by inhibiting farnesyl pyrophosphate synthase in the mevalonate pathway, leading to deficiency of the substrate for GTPase prenylation. Diphosphonates 20-35 farnesyl diphosphate synthase Homo sapiens 83-114 34853276-10 2021 In situ proximity ligation assay (PLA) is used to investigate Rab27a/Doc2a interaction after bisphosphonates (BPs) treatment. Diphosphonates 110-113 RAB27A, member RAS oncogene family Rattus norvegicus 62-68 35482061-14 2022 CONCLUSIONS: The BP-stimulated increase in the level of OPG and the decrease in the level of RANKL, as well as the impact on the level of the analyzed interleukins in the bone microenvironment, may be an important element of the mechanisms limiting bone resorption. Diphosphonates 17-19 TNF receptor superfamily member 11b Homo sapiens 56-59 35482061-14 2022 CONCLUSIONS: The BP-stimulated increase in the level of OPG and the decrease in the level of RANKL, as well as the impact on the level of the analyzed interleukins in the bone microenvironment, may be an important element of the mechanisms limiting bone resorption. Diphosphonates 17-19 TNF superfamily member 11 Homo sapiens 93-98 35593396-0 2022 Bisphosphorylation of anhydrides - convenient access to bisphosphonates with a P-O-C-P motif. Diphosphonates 56-71 proopiomelanocortin Homo sapiens 79-84 35226248-0 2022 Bisphosphonate of Zoledronate Has Antiapoptotic Effect on Hypoxia/Reoxygenation Injury in Human Embryonic Stem Cell-Derived Cardiomyocytes Through Trk Signaling Pathway. Diphosphonates 0-14 neurotrophic receptor tyrosine kinase 1 Homo sapiens 147-150 35102444-19 2022 In the oral bisphosphonates group, the AUCs between TRACP-5b and PINP and TRACP-5b and CTX were significantly different, p < 0.01 and p = 0.001, respectively. Diphosphonates 12-27 acid phosphatase 5, tartrate resistant Homo sapiens 52-60 35102444-19 2022 In the oral bisphosphonates group, the AUCs between TRACP-5b and PINP and TRACP-5b and CTX were significantly different, p < 0.01 and p = 0.001, respectively. Diphosphonates 12-27 acid phosphatase 5, tartrate resistant Homo sapiens 74-82 35102444-19 2022 In the oral bisphosphonates group, the AUCs between TRACP-5b and PINP and TRACP-5b and CTX were significantly different, p < 0.01 and p = 0.001, respectively. Diphosphonates 12-27 cytochrome P450 family 27 subfamily A member 1 Homo sapiens 87-90 34289682-0 2021 Qualitative and quantitative analysis of the CTX in relation to the period of intake of bisphosphonates: A systematic review. Diphosphonates 88-103 cytochrome P450 family 27 subfamily A member 1 Homo sapiens 45-48 34289682-1 2021 The aim of this systematic review was to determinate the true value of C-terminal crosslinking telopeptide test (CTX) in patient who takes Bisphosphonate. Diphosphonates 139-153 cytochrome P450 family 27 subfamily A member 1 Homo sapiens 113-116 34289682-7 2021 This systematic review indicates that the CTX test has diffent predictive value in determining the risk of osteonecrosis in patients taking bisphosphonate compared to previus standard. Diphosphonates 140-154 cytochrome P450 family 27 subfamily A member 1 Homo sapiens 42-45 35619312-8 2022 Based on these findings, TAM-targeted therapeutic strategies, including inhibitors of CSF-1/CSF-1R, CCL2/CCR2, CCL5-CCR5, bisphosphonate, nanoparticle, and exosomal-targeted delivery have been developed, and are currently being employed in intervention trials. Diphosphonates 122-136 Myeloproliferative syndrome, transient (transient abnormal myelopoiesis) Homo sapiens 25-28 35561128-11 2022 In conclusion, bisphosphonate use, especially persistence to intravenous bisphosphonates (e.g., zoledronic acid), may reduce post-fracture mortality among osteoporosis patients, particularly those with hip/vertebral fractures. Diphosphonates 15-29 hedgehog interacting protein Homo sapiens 202-205 35064934-5 2022 Bisphosphonates, such as zoledronic acid (ZOL), which was widely used in MMBD control, could stimulate MAST4 expression in MM cells by promoting ESR1 expression. Diphosphonates 0-15 microtubule associated serine/threonine kinase family member 4 Homo sapiens 103-108 35456610-7 2022 Several SNPs located in genes FDPS and FNTA were associated with the bisphosphonate-induced changes in hip bone mineral density (BMD), whereas polymorphisms of the PDSS1, CYP19A1, CYP1A1, and CYP1A2 genes were associated with SERM-induced changes in spine BMD. Diphosphonates 69-83 farnesyl diphosphate synthase Homo sapiens 30-34 35456610-7 2022 Several SNPs located in genes FDPS and FNTA were associated with the bisphosphonate-induced changes in hip bone mineral density (BMD), whereas polymorphisms of the PDSS1, CYP19A1, CYP1A1, and CYP1A2 genes were associated with SERM-induced changes in spine BMD. Diphosphonates 69-83 farnesyltransferase, CAAX box, alpha Homo sapiens 39-43 35456610-7 2022 Several SNPs located in genes FDPS and FNTA were associated with the bisphosphonate-induced changes in hip bone mineral density (BMD), whereas polymorphisms of the PDSS1, CYP19A1, CYP1A1, and CYP1A2 genes were associated with SERM-induced changes in spine BMD. Diphosphonates 69-83 cytochrome P450 family 19 subfamily A member 1 Homo sapiens 171-178 35456610-7 2022 Several SNPs located in genes FDPS and FNTA were associated with the bisphosphonate-induced changes in hip bone mineral density (BMD), whereas polymorphisms of the PDSS1, CYP19A1, CYP1A1, and CYP1A2 genes were associated with SERM-induced changes in spine BMD. Diphosphonates 69-83 cytochrome P450 family 1 subfamily A member 2 Homo sapiens 192-198 35456610-8 2022 After multivariate analyses, genotypes combining genes FDPS and FNTA showed a stronger association with bisphosphonate response (r = 0.34; p = 0.00009), whereas the combination of CYP19A1 and PDSS1 genotypes was associated with the response to SERMs (r = 0.62, p = 0.0003). Diphosphonates 104-118 farnesyl diphosphate synthase Homo sapiens 55-59 35456610-8 2022 After multivariate analyses, genotypes combining genes FDPS and FNTA showed a stronger association with bisphosphonate response (r = 0.34; p = 0.00009), whereas the combination of CYP19A1 and PDSS1 genotypes was associated with the response to SERMs (r = 0.62, p = 0.0003). Diphosphonates 104-118 farnesyltransferase, CAAX box, alpha Homo sapiens 64-68 35474350-7 2022 Osteoclast survival inhibitor such as alendronate, a bisphosphonate reduced LRF expression. Diphosphonates 53-67 zinc finger and BTB domain containing 7a Mus musculus 76-79 35412438-12 2022 Our findings identified miR-30a-5p as a novel mediator of long-term BP treatment that regulates bone formation in postmenopausal OP patients. Diphosphonates 68-70 microRNA 30a Homo sapiens 24-31 35064934-5 2022 Bisphosphonates, such as zoledronic acid (ZOL), which was widely used in MMBD control, could stimulate MAST4 expression in MM cells by promoting ESR1 expression. Diphosphonates 0-15 estrogen receptor 1 Homo sapiens 145-149 35241520-2 2022 The purpose was to establish a simple local bone metastasis model using normal mice, and to study the usefulness of the model with bisphosphonates (BP). Diphosphonates 131-146 growth differentiation factor 5 Mus musculus 148-150 35370739-9 2022 Since it is involved in bone pain sensation, TRPV1 is a possible alternative target of BPs. Diphosphonates 87-90 transient receptor potential cation channel subfamily V member 1 Homo sapiens 45-50 35220219-9 2022 CONCLUSION: The use of 3D-scaffolds has a positive effect on OB viability, and stimulation by PRF and PRP may provide a therapeutic approach to transfer these results into clinical routine for the treatment of patients with bisphosphonate related osteonecrosis of the jaw (BR-ONJ). Diphosphonates 224-238 prion protein Homo sapiens 102-105 35415073-5 2022 Results: Eight weeks after surgery, the BP + Mg group had significantly reduced occurrence of MRONJ-like lesion and histological osteonecrosis, increased bone microstructural parameters, and increased expressions of VEGFA and CGRP, than the BP + Ti group. Diphosphonates 40-42 vascular endothelial growth factor A Rattus norvegicus 216-221 35415073-5 2022 Results: Eight weeks after surgery, the BP + Mg group had significantly reduced occurrence of MRONJ-like lesion and histological osteonecrosis, increased bone microstructural parameters, and increased expressions of VEGFA and CGRP, than the BP + Ti group. Diphosphonates 40-42 calcitonin-related polypeptide alpha Rattus norvegicus 226-230 35279261-3 2022 Bisphosphonates are the most widely used anti-resorptives, reducing bone turnover markers to low premenopausal concentrations and reducing fracture rates (vertebral by 50-70%, non-vertebral by 20-30%, and hip by ~40%). Diphosphonates 0-15 hedgehog interacting protein Homo sapiens 205-208 35041467-4 2022 RECOMMENDATIONS: Adjuvant bisphosphonate therapy should be discussed with all postmenopausal patients (natural or therapy-induced) with primary breast cancer, irrespective of hormone receptor status and human epidermal growth factor receptor 2 status, who are candidates to receive adjuvant systemic therapy. Diphosphonates 26-40 erb-b2 receptor tyrosine kinase 2 Homo sapiens 209-243 2799693-1 1989 During osteomalacia in patients with terminal renal failure, the coefficient of diphosphonate elimination from the blood bed (K1) was less than 0.1 min-1, which was determined by the rise of the concentration of uremic toxins, inhibiting interaction of the radiopharmaceutical with the bone, in the patients" tissues. Diphosphonates 80-93 CD59 molecule (CD59 blood group) Homo sapiens 148-153 3048274-0 1988 An evaluation of serum osteocalcin in Paget"s disease of bone and its response to diphosphonate treatment. Diphosphonates 82-95 bone gamma-carboxyglutamate protein Homo sapiens 23-34 2848451-0 1988 Diphosphonates are potent inhibitors of mammalian inorganic pyrophosphatase. Diphosphonates 0-14 inorganic pyrophosphatase 1 Homo sapiens 50-75 3748485-0 1986 Which diphosphonate for routine bone scintigraphy (MDP, HDP or DPD)? Diphosphonates 6-19 dihydropyrimidine dehydrogenase Homo sapiens 63-66 2969277-0 1988 Bisphosphonates inhibit 1,25-dihydroxyvitamin D3-induced increase of osteocalcin in plasma of rats in vivo and in culture medium of rat calvaria in vitro. Diphosphonates 0-15 bone gamma-carboxyglutamate protein Rattus norvegicus 69-80 3495547-0 1987 Serum osteocalcin in Paget"s disease of bone: basal concentrations and response to bisphosphonate treatment. Diphosphonates 83-97 bone gamma-carboxyglutamate protein Homo sapiens 6-17 3049432-1 1988 Two new aromatic bis-(2-chloroethyl)-amino derivatives (BCMP and BAD) which are linked to osteotropic bisphosphonates were investigated for their therapeutical efficacy in rat osteosarcoma. Diphosphonates 102-117 BCL2-associated agonist of cell death Rattus norvegicus 56-68 3238315-0 1988 GFR-corrected 24-hour whole body retention of diphosphonate: an improved index of bone metabolism. Diphosphonates 46-59 Rap guanine nucleotide exchange factor 5 Homo sapiens 0-3 3124942-0 1987 The acute-phase response after bisphosphonate administration. Diphosphonates 31-45 phorbol-12-myristate-13-acetate-induced protein 1 Homo sapiens 4-24 3124942-10 1987 These findings suggest that bisphosphonates interact with macrophage-like cells resident in the skeleton and stimulate interleukin-1 release which is responsible for the appearance of the APR. Diphosphonates 28-43 phorbol-12-myristate-13-acetate-induced protein 1 Homo sapiens 188-191 2825741-5 1987 All three diphosphonates induced significant increases in plasma phosphate and tubular reabsorption of phosphate (TmP/GFR). Diphosphonates 10-24 Rap guanine nucleotide exchange factor 5 Homo sapiens 118-121 3862498-3 1985 Initially, bisphosphonates were tested for their effect on the release of [14C]PGE2 from rat calvaria cells labelled with [14C]arachidonic acid and stimulated by bradykinin, thrombin and mechanical manipulation. Diphosphonates 11-26 coagulation factor II Rattus norvegicus 174-182 3014697-0 1986 [Inorganic pyrophosphatase activity of the mouse spleen in the immune response and after treatment with bis-phosphonates]. Diphosphonates 104-120 pyrophosphatase (inorganic) 1 Mus musculus 1-26 3006732-2 1985 Since interleukin 1 (IL-1)-like activity has been shown to stimulate bone resorption in vitro, we have studied whether bisphosphonates inhibit either the production of IL-1-like activity or its effect on one type of connective tissue cell, chondrocytes. Diphosphonates 119-134 interleukin 1 complex Mus musculus 168-172 3006732-4 1985 Production of IL-1-like activity was unaffected by bisphosphonates, whereas the effect of IL-1-like activity on collagenase and prostaglandin E2 secretion by rabbit chondrocytes was increased rather than inhibited by bisphosphonates. Diphosphonates 217-232 interleukin 1 complex Mus musculus 90-94 3006732-5 1985 Finally, bisphosphonates increased DNA and cell number in chondrocyte cultures, but this effect was blocked when IL-1-like activity was added to the cultures. Diphosphonates 9-24 interleukin 1 complex Mus musculus 113-117 4006990-0 1985 Liver uptake of 99mTc-labeled diphosphonate (DPD) by metastatic lesions from large bowel carcinoma. Diphosphonates 30-43 dihydropyrimidine dehydrogenase Homo sapiens 45-48 6138019-2 1983 diphosphonate, methane-diphosphonate and dichloromethane diphosphonate, on inorganic pyrophosphatase (PPiase, E.C. Diphosphonates 0-13 inorganic pyrophosphatase 1 Rattus norvegicus 75-100 6623666-4 1983 An increase in the Mg2+ concentration to the [Mg2+]/[S] = 40 ratio lowers the inhibition degree for all three diphosphonates; it follows a mixed mechanism. Diphosphonates 110-124 mucin 7, secreted Homo sapiens 19-22 6623666-4 1983 An increase in the Mg2+ concentration to the [Mg2+]/[S] = 40 ratio lowers the inhibition degree for all three diphosphonates; it follows a mixed mechanism. Diphosphonates 110-124 mucin 7, secreted Homo sapiens 46-49 6623666-5 1983 Thus, the inhibition of the alkaline phosphatase activity by diphosphonic acids is due to both competition of the inhibitor for the enzyme active centre and a decrease in the Mg2+ concentration, the phosphatase activator, because of Mg2+ complexing with diphosphonates. Diphosphonates 254-268 mucin 7, secreted Homo sapiens 175-178 6623666-5 1983 Thus, the inhibition of the alkaline phosphatase activity by diphosphonic acids is due to both competition of the inhibitor for the enzyme active centre and a decrease in the Mg2+ concentration, the phosphatase activator, because of Mg2+ complexing with diphosphonates. Diphosphonates 254-268 mucin 7, secreted Homo sapiens 233-236 6138019-6 1983 The influence of calcium and inorganic phosphate (Pi) on the PPiase activity was studied in the presence and absence of several complexing substances, including the diphosphonates. Diphosphonates 165-179 FKBP prolyl isomerase family member 6 Rattus norvegicus 61-67 6236769-5 1984 The bone resorbing effect caused by PHA-stimulated cells was blocked by dichloromethylene diphosphonate at 10(-5) M concentration, but mononuclear cells preincubated in diphosphonate containing media were capable to resorb fetal rat bone in tissue culture. Diphosphonates 90-103 lamin B receptor Homo sapiens 36-39 6138019-2 1983 diphosphonate, methane-diphosphonate and dichloromethane diphosphonate, on inorganic pyrophosphatase (PPiase, E.C. Diphosphonates 0-13 FKBP prolyl isomerase family member 6 Rattus norvegicus 102-108 6127784-8 1982 The diphosphonates ethane-1-hydroxy 1,1 diphosphonate (EHDP), methane diphosphonate (MDP) and dichloromethane diphosphonate (Cl2MDP) inhibited the PPiase activity. Diphosphonates 4-18 FKBP prolyl isomerase 1B Homo sapiens 147-153 4204000-0 1974 Parathyroid hormone effects in rats treated with diphosphonate. Diphosphonates 49-62 parathyroid hormone Rattus norvegicus 0-19 6177249-7 1982 In fact, the role of NaF therapy could already be taken over by diphosphonates currently under study. Diphosphonates 64-78 C-X-C motif chemokine ligand 8 Homo sapiens 21-24 7389273-6 1980 When the patients with Paget"s disease were treated with either diphosphonate or calcitonin, the plasma alpha 2HS-glycoprotein concentration increased towards normal. Diphosphonates 64-77 alpha 2-HS glycoprotein Homo sapiens 104-126 208419-0 1978 Parathyroid hormone and renal handling of Pi: effect of dietary Pi and diphosphonates. Diphosphonates 71-85 parathyroid hormone Homo sapiens 0-19 6259795-0 1981 [Effect of inorganic pyrophosphate and its diphosphonate analogs on glucose-6-phosphatase dehydrogenase activity of mouse organs]. Diphosphonates 43-56 glucose-6-phosphatase, catalytic Mus musculus 68-89 33836308-0 2021 Local RANKL delivery improves socket healing in bisphosphonate treated rats. Diphosphonates 48-62 TNF superfamily member 11 Rattus norvegicus 6-11 11946677-0 1972 Effects of pyrophosphate and diphosphonates on parathyroid hormone- and fluoride-stimulated adenylate cyclase activity. Diphosphonates 29-43 parathyroid hormone Homo sapiens 47-66 33836308-3 2021 Here, we investigated if local application of RANKL (a key molecule in osteoclast activation) could enhance osteoclast generation and improve extraction socket healing in the presence of bisphosphonates. Diphosphonates 187-202 TNF superfamily member 11 Rattus norvegicus 46-51 34026748-1 2021 Background: Bisphosphonates are drugs widely used to reduce bone resorption, increase bone mineral density and control age-related bone loss. Diphosphonates 12-27 renin binding protein Rattus norvegicus 119-122 33559705-2 2021 Among the bisphosphonates, the non-amino-bisphosphonates, such as clodronic acid, are intracellular converted into toxic analogues of ATP and induce cellular apoptosis whereas the amino-bisphosphonates, such as zoledronic acid, inhibit the farnesyl-diphosphate-synthase, an enzyme of the mevalonate pathway. Diphosphonates 10-25 farnesyl diphosphate synthase Homo sapiens 240-269 33559705-2 2021 Among the bisphosphonates, the non-amino-bisphosphonates, such as clodronic acid, are intracellular converted into toxic analogues of ATP and induce cellular apoptosis whereas the amino-bisphosphonates, such as zoledronic acid, inhibit the farnesyl-diphosphate-synthase, an enzyme of the mevalonate pathway. Diphosphonates 41-56 farnesyl diphosphate synthase Homo sapiens 240-269 33386876-2 2021 Our meta-analysis of studies shows that early bisphosphonate administration after SCI was safe and beneficial to the BMD of the total hip and lumbar spine at 12 months. Diphosphonates 46-60 hedgehog interacting protein Homo sapiens 134-137 33386876-10 2021 RESULTS: There were significant differences in BMD of the total hip and lumbar spine or serum C-terminal telopeptide between the bisphosphonate and control groups but no difference in adverse events. Diphosphonates 129-143 hedgehog interacting protein Homo sapiens 64-67 33386876-14 2021 CONCLUSION: Early bisphosphonate administration after SCI was safe and beneficial to the BMD of the total hip and lumbar spine at 12 months. Diphosphonates 18-32 hedgehog interacting protein Homo sapiens 106-109 34055774-0 2021 Adipose-Derived Stem Cells Promote Bone Coupling in Bisphosphonate-Related Osteonecrosis of the Jaw by TGF-beta1. Diphosphonates 52-66 transforming growth factor beta 1 Homo sapiens 103-112 33592328-3 2021 The immunomodulatory capacity of BPs has been focused on the mechanisms involved in the acute-phase response associated with the administration of nitrogen containing BPs (N-BPs), with the stimulus of pro-inflammatory cytokines, through the mevalonate pathway, activation of T-cells and the decrease in the cytotoxic T-lymphocyte antigen-4 (CTLA-4). Diphosphonates 33-36 cytotoxic T-lymphocyte associated protein 4 Homo sapiens 307-339 33791863-20 2021 These results support that conjugation of Ang1-7 with bisphosphonate enables it to utilize bone as a reservoir for the sustained delivery of Ang1-7 to maintain therapeutic plasma levels. Diphosphonates 54-68 angiogenin Rattus norvegicus 42-48 33791863-20 2021 These results support that conjugation of Ang1-7 with bisphosphonate enables it to utilize bone as a reservoir for the sustained delivery of Ang1-7 to maintain therapeutic plasma levels. Diphosphonates 54-68 angiogenin Rattus norvegicus 141-147 33592328-3 2021 The immunomodulatory capacity of BPs has been focused on the mechanisms involved in the acute-phase response associated with the administration of nitrogen containing BPs (N-BPs), with the stimulus of pro-inflammatory cytokines, through the mevalonate pathway, activation of T-cells and the decrease in the cytotoxic T-lymphocyte antigen-4 (CTLA-4). Diphosphonates 33-36 cytotoxic T-lymphocyte associated protein 4 Homo sapiens 341-347 33592328-3 2021 The immunomodulatory capacity of BPs has been focused on the mechanisms involved in the acute-phase response associated with the administration of nitrogen containing BPs (N-BPs), with the stimulus of pro-inflammatory cytokines, through the mevalonate pathway, activation of T-cells and the decrease in the cytotoxic T-lymphocyte antigen-4 (CTLA-4). Diphosphonates 167-170 cytotoxic T-lymphocyte associated protein 4 Homo sapiens 307-339 33592328-3 2021 The immunomodulatory capacity of BPs has been focused on the mechanisms involved in the acute-phase response associated with the administration of nitrogen containing BPs (N-BPs), with the stimulus of pro-inflammatory cytokines, through the mevalonate pathway, activation of T-cells and the decrease in the cytotoxic T-lymphocyte antigen-4 (CTLA-4). Diphosphonates 167-170 cytotoxic T-lymphocyte associated protein 4 Homo sapiens 341-347 33694194-2 2021 Bisphosphonates were shown to ameliorate dementia in osteoporotic patients, neuroinflammation, and cholinesterase activity in rodents. Diphosphonates 0-15 butyrylcholinesterase Homo sapiens 99-113 33852064-0 2021 Effects of EGF-coated titanium surfaces on adhesion and metabolism of bisphosphonate-treated human keratinocytes and gingival fibroblasts. Diphosphonates 70-84 epidermal growth factor Homo sapiens 11-14 33852064-11 2021 CLINICAL RELEVANCE: EGF-coating on titanium may be a suitable strategy to improve oral mucosa cellular events related to biological sealing, especially for patients under bisphosphonate therapy. Diphosphonates 171-185 epidermal growth factor Homo sapiens 20-23 33837656-4 2021 MATERIALS AND METHODS: The expression of MRONJ-related miRNA in RANKL-induced RAW264.7 cells treated with BP was analyzed using qRT-PCR analysis. Diphosphonates 106-108 tumor necrosis factor (ligand) superfamily, member 11 Mus musculus 64-69 33662239-0 2021 Improving Bisphosphonate Use and Evaluation in a Rural Family Medicine Practice. Diphosphonates 10-24 PRAC1 small nuclear protein Homo sapiens 71-79 32885992-3 2021 OBJECTIVE: The objective of this study was to compare the use of bisphosphonate versus bisphosphonate with calcitonin for moderate to severe hypercalcemia of malignancy. Diphosphonates 87-101 calcitonin related polypeptide alpha Homo sapiens 107-117 32885992-5 2021 Patients received usual care plus either (1) bisphosphonate or (2) bisphosphonate with calcitonin. Diphosphonates 67-81 calcitonin related polypeptide alpha Homo sapiens 87-97 32885992-12 2021 CONCLUSIONS AND RELEVANCE: In the treatment of moderate to severe hypercalcemia of malignancy, IV bisphosphonate in combination with calcitonin resulted in a higher difference in corrected calcium levels at 48 hours compared with bisphosphonate therapy alone. Diphosphonates 230-244 calcitonin related polypeptide alpha Homo sapiens 133-143 33183068-5 2021 To the contrary, long-term use of anti-osteoporotic drugs such as bisphosphonates and Denosumab, an RANKL inhibitor, have resulted in adverse events. Diphosphonates 66-81 TNF superfamily member 11 Homo sapiens 100-105 33398631-2 2021 We previously showed that nitrogen-containing bisphosphonate (NBP)-treatment induces extramedullary hematopoiesis via G-CSF stimulation. Diphosphonates 46-60 colony stimulating factor 3 (granulocyte) Mus musculus 118-123 32885992-1 2021 BACKGROUND: Historically, intravenous (IV) bisphosphonates with calcitonin are the treatment of choice for hypercalcemia of malignancy. Diphosphonates 43-58 calcitonin related polypeptide alpha Homo sapiens 64-74 33296741-0 2021 In silico exploration of binding of selected bisphosphonate derivatives to placental alkaline phosphatase via docking and molecular dynamics. Diphosphonates 45-59 alkaline phosphatase, placental Homo sapiens 75-105 33662239-6 2021 PRACTICE INNOVATION: The pharmacy team and medical resident collaborated to determine appropriateness of bisphosphonate use. Diphosphonates 105-119 PRAC1 small nuclear protein Homo sapiens 0-8 32530102-1 2021 AIMS: To evaluate whether 2 years of treatment with bisphosphonates in combination with calcium/vitamin D supplements has an effect on lumbar spine and hip bone mineral density (BMD) in ankylosing spondylitis (AS) patients starting tumor necrosis factor-alpha (TNF-alpha) inhibitors or receiving conventional treatment. Diphosphonates 52-67 tumor necrosis factor Homo sapiens 232-259 33722457-8 2021 In perspective, preoperative PTH use may represent a better prophylactic regimen for preventing the occurrence of MRONJ after traumatic dental or surgical procedures, especially in patients with a history of long-term bisphosphonate administration or at high risk of developing MRONJ. Diphosphonates 218-232 parathyroid hormone Homo sapiens 29-32 32530102-1 2021 AIMS: To evaluate whether 2 years of treatment with bisphosphonates in combination with calcium/vitamin D supplements has an effect on lumbar spine and hip bone mineral density (BMD) in ankylosing spondylitis (AS) patients starting tumor necrosis factor-alpha (TNF-alpha) inhibitors or receiving conventional treatment. Diphosphonates 52-67 tumor necrosis factor Homo sapiens 261-270 33284101-13 2021 Most of the patients (87.1%) treated with intravenous bisphosphonates responded well, with a decrease in serum ALP level (117+-114 IU/L) in the 12th month of therapy. Diphosphonates 54-69 alkaline phosphatase, placental Homo sapiens 111-114 32897500-0 2021 Bisphosphonate-related osteonecrosis induced change in alveolar bone architecture in rats with participation of Wnt signaling. Diphosphonates 0-14 Wnt family member 10B Rattus norvegicus 112-115 32967053-2 2021 Our previous whole-exome sequencing study found SIRT1 intronic region SNP rs7896005 to be associated with MRONJ in cancer patients treated with intravenous (IV) bisphosphonates (BPs). Diphosphonates 161-176 sirtuin 1 Homo sapiens 48-53 32967053-2 2021 Our previous whole-exome sequencing study found SIRT1 intronic region SNP rs7896005 to be associated with MRONJ in cancer patients treated with intravenous (IV) bisphosphonates (BPs). Diphosphonates 178-181 sirtuin 1 Homo sapiens 48-53 33479844-3 2021 In our population including 14,990 women and 13,239 men, use of bisphosphonates reduced risk of fractures in hip and forearm in women. Diphosphonates 64-79 hedgehog interacting protein Homo sapiens 109-112 33479844-5 2021 INTRODUCTION: The objective was to examine if treatment with bisphosphonates (BPs) was associated with reduced risk of fractures in the hip and forearm in women and men in the general population. Diphosphonates 61-76 hedgehog interacting protein Homo sapiens 136-139 33479844-5 2021 INTRODUCTION: The objective was to examine if treatment with bisphosphonates (BPs) was associated with reduced risk of fractures in the hip and forearm in women and men in the general population. Diphosphonates 78-81 hedgehog interacting protein Homo sapiens 136-139 33374546-0 2020 Bisphosphonates Reduce Smoking-Induced Osteoporotic-Like Alterations by Regulating RANKL/OPG in an Osteoblast and Osteoclast Co-Culture Model. Diphosphonates 0-15 TNF superfamily member 11 Homo sapiens 83-88 33374546-0 2020 Bisphosphonates Reduce Smoking-Induced Osteoporotic-Like Alterations by Regulating RANKL/OPG in an Osteoblast and Osteoclast Co-Culture Model. Diphosphonates 0-15 TNF receptor superfamily member 11b Homo sapiens 89-92 33374546-5 2020 Our results showed that BPs were able to reduce CSE-induced osteoporotic alterations in the co-culture of osteoblasts and osteoclasts such as decreased matrix remodeling, enhanced osteoclast activation, and an up-regulated receptor activator of nuclear factor (NF)-kB-ligand (RANKL)/osteoprotegerin (OPG) ratio. Diphosphonates 24-27 TNF superfamily member 11 Homo sapiens 276-281 33374546-5 2020 Our results showed that BPs were able to reduce CSE-induced osteoporotic alterations in the co-culture of osteoblasts and osteoclasts such as decreased matrix remodeling, enhanced osteoclast activation, and an up-regulated receptor activator of nuclear factor (NF)-kB-ligand (RANKL)/osteoprotegerin (OPG) ratio. Diphosphonates 24-27 TNF receptor superfamily member 11b Homo sapiens 283-298 33374546-5 2020 Our results showed that BPs were able to reduce CSE-induced osteoporotic alterations in the co-culture of osteoblasts and osteoclasts such as decreased matrix remodeling, enhanced osteoclast activation, and an up-regulated receptor activator of nuclear factor (NF)-kB-ligand (RANKL)/osteoprotegerin (OPG) ratio. Diphosphonates 24-27 TNF receptor superfamily member 11b Homo sapiens 300-303 33374546-6 2020 In summary, BPs may be an effective alternative therapy for reversing osteoporotic alterations in smokers, and the potential mechanism is through modulation of the RANKL/OPG ratio. Diphosphonates 12-15 TNF superfamily member 11 Homo sapiens 164-169 33374546-6 2020 In summary, BPs may be an effective alternative therapy for reversing osteoporotic alterations in smokers, and the potential mechanism is through modulation of the RANKL/OPG ratio. Diphosphonates 12-15 TNF receptor superfamily member 11b Homo sapiens 170-173 33718013-3 2021 Accordingly, our aim was to investigate the impact of KRAS mutation on bisphosphonate (BTx) and radiation therapy (RTx) in bone-metastatic LADC patients. Diphosphonates 71-85 KRAS proto-oncogene, GTPase Homo sapiens 54-58 33420145-0 2021 Effects of pre-extraction intermittent PTH administration on extraction socket healing in bisphosphonate administered ovariectomized rats. Diphosphonates 90-104 parathyroid hormone Rattus norvegicus 39-42 33188959-3 2021 Although bisphosphonates reduce bone formation by 70-90% in subjects with normal GFR and reduce the ability of bone to buffer exogenous calcium fluxes, in bisphosphonate treated postmenopausal women accelerated vascular calcification has not been documented. Diphosphonates 9-23 Rap guanine nucleotide exchange factor 5 Homo sapiens 81-84 32735740-0 2021 Pharmacological evaluation of imidazole-derived bisphosphonates on RANKL-induced osteoclast differentiation and function. Diphosphonates 48-63 tumor necrosis factor (ligand) superfamily, member 11 Mus musculus 67-72 32944291-5 2020 Scintigraphy with a diphosphonate tracer is a diagnostic tool for the early detection of cardiac ATTR amyloidosis with high sensitivity and specificity. Diphosphonates 20-33 transthyretin Homo sapiens 97-101 33141482-11 2021 Serum bone-specific alkaline phosphatase and tartrate-resistant acid phosphatase 5b were significantly decreased in the BP-Dmab and SERM-Dmab groups compared with the BP-BP and SERM-SERM groups, respectively. Diphosphonates 120-122 acid phosphatase 5, tartrate resistant Homo sapiens 45-83 32537808-2 2020 Nitrogen-containing bisphosphonates, a current treatment for bone diseases, have been shown to block the growth of the T. brucei parasites by inhibiting farnesyl pyrophosphate synthase (FPPS); however, due to their poor pharmacokinetic properties they are not well suited for anti-parasitic therapy. Diphosphonates 20-35 farnesyl diphosphate synthase Homo sapiens 186-190 32115673-7 2020 The clinical manifestations of PDB patients in mainland China mainly included ostealgia, bone malformation, hearing loss, and fracture, and bisphosphonate was used as the main treatment drug. Diphosphonates 140-154 PDB1 Homo sapiens 31-34 32603908-1 2020 Acute phase response (APR) following intravenous zoledronate (ZOL) administration is related to activation and increased proliferation of gammadelta T cells, attributed to the molecular mechanism of action of nitrogen-containing bisphosphonates (N-BPs). Diphosphonates 229-244 phorbol-12-myristate-13-acetate-induced protein 1 Homo sapiens 22-25 32786371-0 2021 [68Ga]Ga-THP-Pam: A Bisphosphonate PET tracer with Facile Radiolabelling and Broad Calcium Mineral Affinity. Diphosphonates 20-34 peptidylglycine alpha-amidating monooxygenase Homo sapiens 13-16 32276287-9 2020 Bisphosphonate treatment reduced osteocalcin, osteoprotegerin, osteopontin, BMP2, PGE2, TGFbeta1, IL10, and VEGF in MG63 cells. Diphosphonates 0-14 bone gamma-carboxyglutamate protein Homo sapiens 33-44 33244490-9 2020 Conclusion: Combination therapy including asfotase alfa with rhBMP-2 and bisphosphonate resulted in solid arthrodesis after spinal surgery in NF1-related dystrophic scoliosis. Diphosphonates 73-87 neurofibromin 1 Homo sapiens 142-145 32181939-4 2020 By whole exome sequencing, we identified a homozygous variant (c.2T>C) in CCDC134 gene in three patients from two unrelated families, with severe bone fragility which did not respond to bisphosphonate treatment, short stature, gracile long bones with pseudarthroses, but no dentinogenesis imperfecta. Diphosphonates 186-200 coiled-coil domain containing 134 Homo sapiens 74-81 32276287-9 2020 Bisphosphonate treatment reduced osteocalcin, osteoprotegerin, osteopontin, BMP2, PGE2, TGFbeta1, IL10, and VEGF in MG63 cells. Diphosphonates 0-14 TNF receptor superfamily member 11b Homo sapiens 46-61 32276287-9 2020 Bisphosphonate treatment reduced osteocalcin, osteoprotegerin, osteopontin, BMP2, PGE2, TGFbeta1, IL10, and VEGF in MG63 cells. Diphosphonates 0-14 secreted phosphoprotein 1 Homo sapiens 63-74 32276287-9 2020 Bisphosphonate treatment reduced osteocalcin, osteoprotegerin, osteopontin, BMP2, PGE2, TGFbeta1, IL10, and VEGF in MG63 cells. Diphosphonates 0-14 bone morphogenetic protein 2 Homo sapiens 76-80 32276287-9 2020 Bisphosphonate treatment reduced osteocalcin, osteoprotegerin, osteopontin, BMP2, PGE2, TGFbeta1, IL10, and VEGF in MG63 cells. Diphosphonates 0-14 transforming growth factor beta 1 Homo sapiens 88-96 32276287-9 2020 Bisphosphonate treatment reduced osteocalcin, osteoprotegerin, osteopontin, BMP2, PGE2, TGFbeta1, IL10, and VEGF in MG63 cells. Diphosphonates 0-14 interleukin 10 Homo sapiens 98-102 32276287-9 2020 Bisphosphonate treatment reduced osteocalcin, osteoprotegerin, osteopontin, BMP2, PGE2, TGFbeta1, IL10, and VEGF in MG63 cells. Diphosphonates 0-14 vascular endothelial growth factor A Homo sapiens 108-112 32490054-15 2020 Discussion: We believe, this is the first report of skeletal changes suggestive of HPP, arising secondary to antenatal etidronate (first generation bisphosphonate) used for the treatment of suspected GACI due to a heterozygous ABCC6 mutation. Diphosphonates 148-162 ATP binding cassette subfamily C member 6 Homo sapiens 227-232 32274606-3 2020 In our previous study, we reported that the expression of the gene encoding nuclear factor of activated T cells c1 (NFATc1), a known osteoclast differentiation marker, was significantly silenced by zoledronate, a bisphosphonate, in mouse osteoclast precursor cells (mOCPCs) using cDNA microarray. Diphosphonates 213-227 nuclear factor of activated T cells, cytoplasmic, calcineurin dependent 1 Mus musculus 76-114 32274606-3 2020 In our previous study, we reported that the expression of the gene encoding nuclear factor of activated T cells c1 (NFATc1), a known osteoclast differentiation marker, was significantly silenced by zoledronate, a bisphosphonate, in mouse osteoclast precursor cells (mOCPCs) using cDNA microarray. Diphosphonates 213-227 nuclear factor of activated T cells, cytoplasmic, calcineurin dependent 1 Mus musculus 116-122 32274606-10 2020 The understanding of the role of VEGFR2 on bone remodeling is important to elucidate the pathogenesis of bisphosphonate-related ONJ. Diphosphonates 105-119 kinase insert domain receptor Homo sapiens 33-39 32217159-2 2020 We previously demonstrated that sialic acid-binding immunoglobulin-like lectin 15 (Siglec-15) targeting therapy, which interferes with osteoclast terminal differentiation in the secondary, but not primary, spongiosa, increased bone mass without adverse effects on skeletal growth, whereas bisphosphonate, a first-line treatment for osteoporosis, increased bone mass but impaired long bone growth in healthy growing rats. Diphosphonates 289-303 sialic acid binding Ig-like lectin 15 Rattus norvegicus 83-92 32081469-1 2020 BACKGROUND: Planar diphosphonate scintigraphy is an established diagnostic tool for amyloid transthyretin (ATTR) cardiomyopathy. Diphosphonates 19-32 transthyretin Homo sapiens 84-105 32081469-1 2020 BACKGROUND: Planar diphosphonate scintigraphy is an established diagnostic tool for amyloid transthyretin (ATTR) cardiomyopathy. Diphosphonates 19-32 transthyretin Homo sapiens 107-111 31902117-11 2020 In vivo experiments with KRAS mutant xenograft model also revealed growth inhibitory potential of bisphosphonate treatment. Diphosphonates 98-112 KRAS proto-oncogene, GTPase Homo sapiens 25-29 32434850-0 2020 ATRAID regulates the action of nitrogen-containing bisphosphonates on bone. Diphosphonates 51-66 all-trans retinoic acid induced differentiation factor Homo sapiens 0-6 32426015-2 2020 Offset of bisphosphonate effect may therefore be monitored by measuring C-terminal telopeptide (CTX) following long-term bisphosphonate treatment to inform clinical decisions on drug holiday. Diphosphonates 10-24 cytochrome P450 family 27 subfamily A member 1 Homo sapiens 96-99 31872255-10 2020 The levels of miR-181c-5p and miR-497-5p were decreased in the serum of postmenopausal women with osteopenia or osteoporosis, but increased in subjects treated with bisphosphonate plus calcitriol. Diphosphonates 165-179 microRNA 181c Homo sapiens 14-22 32289617-4 2020 Exposure to bisphosphonates was characterized based on cumulative doses (proportion of days covered, PDC). Diphosphonates 12-27 phosducin Homo sapiens 101-104 32426015-10 2020 We suggest CTX monitoring could identify those not experiencing a sustained bisphosphonate effect, including poorly adherence to therapy, and may be used during a drug holiday to prompt recommencement of therapy. Diphosphonates 76-90 cytochrome P450 family 27 subfamily A member 1 Homo sapiens 11-14 32057422-1 2020 Farnesyl pyrophosphate synthase (FPPS) is a crucial enzyme for the synthesis of isoprenoids and the key target of nitrogen-containing bisphosphonates (N-BPs). Diphosphonates 134-149 farnesyl diphosphate synthase Homo sapiens 0-31 32057422-1 2020 Farnesyl pyrophosphate synthase (FPPS) is a crucial enzyme for the synthesis of isoprenoids and the key target of nitrogen-containing bisphosphonates (N-BPs). Diphosphonates 134-149 farnesyl diphosphate synthase Homo sapiens 33-37 31872255-10 2020 The levels of miR-181c-5p and miR-497-5p were decreased in the serum of postmenopausal women with osteopenia or osteoporosis, but increased in subjects treated with bisphosphonate plus calcitriol. Diphosphonates 165-179 microRNA 497 Homo sapiens 30-37 32001068-6 2020 When transition of calcium-phosphate precipitates from the amorphous phase to the crystalline phase was blocked by bisphosphonate, the calciprotein particle size was reduced and FGF23 expression was augmented, suggesting that small calciprotein particles containing amorphous calcium-phosphate precipitates function as a more potent FGF23 inducer than larger calciprotein particles containing crystalline calcium-phosphate precipitates. Diphosphonates 115-129 fibroblast growth factor 23 Mus musculus 178-183 32001068-6 2020 When transition of calcium-phosphate precipitates from the amorphous phase to the crystalline phase was blocked by bisphosphonate, the calciprotein particle size was reduced and FGF23 expression was augmented, suggesting that small calciprotein particles containing amorphous calcium-phosphate precipitates function as a more potent FGF23 inducer than larger calciprotein particles containing crystalline calcium-phosphate precipitates. Diphosphonates 115-129 fibroblast growth factor 23 Mus musculus 333-338 31863962-8 2020 Inasmuch as incubation of the myotubes with an antibody to transforming growth factor beta (TGFbeta) rescued myotube size in the cultures with serum from patients who received the placebo to the same magnitude as cultures with serum from patients treated with single dose bisphosphonate, we postulate that post-burn bone resorption liberates muscle catabolic factors which cause muscle wasting. Diphosphonates 272-286 transforming growth factor beta 1 Homo sapiens 59-90 32395390-2 2020 The aim of this study was to investigate the effect of intermittent administration of parathyroid hormone (PTH) on peri-implant bone in the maxillae of ovariectomized rats systemically administered BPs. Diphosphonates 198-201 parathyroid hormone Rattus norvegicus 86-105 32395390-2 2020 The aim of this study was to investigate the effect of intermittent administration of parathyroid hormone (PTH) on peri-implant bone in the maxillae of ovariectomized rats systemically administered BPs. Diphosphonates 198-201 parathyroid hormone Rattus norvegicus 107-110 31863962-8 2020 Inasmuch as incubation of the myotubes with an antibody to transforming growth factor beta (TGFbeta) rescued myotube size in the cultures with serum from patients who received the placebo to the same magnitude as cultures with serum from patients treated with single dose bisphosphonate, we postulate that post-burn bone resorption liberates muscle catabolic factors which cause muscle wasting. Diphosphonates 272-286 transforming growth factor beta 1 Homo sapiens 92-99 31738647-5 2020 Interestingly, XPD transduction and treatment with statins and bisphosphonates known to accelerate the radiation-induced ATM nucleo-shuttling led to significant complementation of these impairments.Conclusions: Our findings suggest that some subsets of XPD patients may be at risk of radiosensitivity reactions and treatment with statins and bisphosphonates may be an interesting approach of radioprotection countermeasure. Diphosphonates 63-78 ERCC excision repair 2, TFIIH core complex helicase subunit Homo sapiens 15-18 31738647-5 2020 Interestingly, XPD transduction and treatment with statins and bisphosphonates known to accelerate the radiation-induced ATM nucleo-shuttling led to significant complementation of these impairments.Conclusions: Our findings suggest that some subsets of XPD patients may be at risk of radiosensitivity reactions and treatment with statins and bisphosphonates may be an interesting approach of radioprotection countermeasure. Diphosphonates 63-78 ATM serine/threonine kinase Homo sapiens 121-124 31445964-11 2020 CYP2C8 rs1934951 (in multiple myeloma patients) and VEGF rs3025039 are associated with the development of MRONJ in patients treated with bisphosphonates. Diphosphonates 137-152 cytochrome P450 family 2 subfamily C member 8 Homo sapiens 0-6 31738647-5 2020 Interestingly, XPD transduction and treatment with statins and bisphosphonates known to accelerate the radiation-induced ATM nucleo-shuttling led to significant complementation of these impairments.Conclusions: Our findings suggest that some subsets of XPD patients may be at risk of radiosensitivity reactions and treatment with statins and bisphosphonates may be an interesting approach of radioprotection countermeasure. Diphosphonates 63-78 ERCC excision repair 2, TFIIH core complex helicase subunit Homo sapiens 253-256 31445964-11 2020 CYP2C8 rs1934951 (in multiple myeloma patients) and VEGF rs3025039 are associated with the development of MRONJ in patients treated with bisphosphonates. Diphosphonates 137-152 vascular endothelial growth factor A Homo sapiens 52-56 31738647-5 2020 Interestingly, XPD transduction and treatment with statins and bisphosphonates known to accelerate the radiation-induced ATM nucleo-shuttling led to significant complementation of these impairments.Conclusions: Our findings suggest that some subsets of XPD patients may be at risk of radiosensitivity reactions and treatment with statins and bisphosphonates may be an interesting approach of radioprotection countermeasure. Diphosphonates 342-357 ERCC excision repair 2, TFIIH core complex helicase subunit Homo sapiens 15-18 31738647-5 2020 Interestingly, XPD transduction and treatment with statins and bisphosphonates known to accelerate the radiation-induced ATM nucleo-shuttling led to significant complementation of these impairments.Conclusions: Our findings suggest that some subsets of XPD patients may be at risk of radiosensitivity reactions and treatment with statins and bisphosphonates may be an interesting approach of radioprotection countermeasure. Diphosphonates 342-357 ATM serine/threonine kinase Homo sapiens 121-124 31738647-5 2020 Interestingly, XPD transduction and treatment with statins and bisphosphonates known to accelerate the radiation-induced ATM nucleo-shuttling led to significant complementation of these impairments.Conclusions: Our findings suggest that some subsets of XPD patients may be at risk of radiosensitivity reactions and treatment with statins and bisphosphonates may be an interesting approach of radioprotection countermeasure. Diphosphonates 342-357 ERCC excision repair 2, TFIIH core complex helicase subunit Homo sapiens 253-256 31606424-8 2020 Bisphosphonate (P < .001) and mixed necrosis (P = .002) demonstrated more RANKL- and TRAP-positive osteoclasts. Diphosphonates 0-14 TNF superfamily member 11 Homo sapiens 77-82 31996109-15 2020 CONCLUSIONS: In clinical practice, fewer SLE patients with or at risk for GIOP are prescribed vitamin D and bisphosphonates than recommended by the 2017 ACR guidelines. Diphosphonates 108-123 acrosin Homo sapiens 153-156 31785819-0 2020 Structure-based virtual screening and biological evaluation of novel non-bisphosphonate farnesyl pyrophosphate synthase inhibitors. Diphosphonates 73-87 farnesyl diphosphate synthase Homo sapiens 88-119 31785819-1 2020 Farnesyl pyrophosphate synthase (FPPS) is known to participate in a variety of disease-related cell signaling pathway and bisphosphonates (BPs) are served as FPPS inhibitors. Diphosphonates 122-137 farnesyl diphosphate synthase Homo sapiens 0-31 31785819-1 2020 Farnesyl pyrophosphate synthase (FPPS) is known to participate in a variety of disease-related cell signaling pathway and bisphosphonates (BPs) are served as FPPS inhibitors. Diphosphonates 122-137 farnesyl diphosphate synthase Homo sapiens 33-37 31785819-1 2020 Farnesyl pyrophosphate synthase (FPPS) is known to participate in a variety of disease-related cell signaling pathway and bisphosphonates (BPs) are served as FPPS inhibitors. Diphosphonates 122-137 farnesyl diphosphate synthase Homo sapiens 158-162 31821387-5 2019 In case of lung adenocarcinoma bisphosphonate treatment inhibited both wild-type and mutated K-RAS, although tumor cells carrying mutated K-RAS seemed to be more sensitive to the bisphosphonate treatment. Diphosphonates 31-45 KRAS proto-oncogene, GTPase Homo sapiens 93-98 31785819-1 2020 Farnesyl pyrophosphate synthase (FPPS) is known to participate in a variety of disease-related cell signaling pathway and bisphosphonates (BPs) are served as FPPS inhibitors. Diphosphonates 139-142 farnesyl diphosphate synthase Homo sapiens 0-31 31785819-1 2020 Farnesyl pyrophosphate synthase (FPPS) is known to participate in a variety of disease-related cell signaling pathway and bisphosphonates (BPs) are served as FPPS inhibitors. Diphosphonates 139-142 farnesyl diphosphate synthase Homo sapiens 33-37 31785819-1 2020 Farnesyl pyrophosphate synthase (FPPS) is known to participate in a variety of disease-related cell signaling pathway and bisphosphonates (BPs) are served as FPPS inhibitors. Diphosphonates 139-142 farnesyl diphosphate synthase Homo sapiens 158-162 31935810-2 2020 Herein, the synthesis of a macromolecular spirocyclic phosphorus/nitrogen-containing IFR poly sulfonamide spirocyclic pentaerythritol bisphosphonate (SAPC) is reported via a two-step method that uses pentaerythritol, phosphorus oxychloride and sulfonamide (SAA) as raw materials. Diphosphonates 89-148 serum amyloid A1 cluster Homo sapiens 257-260 31699606-3 2019 The lead carboxyphosphonate inhibits geranylgeranyl transferase II while its corresponding bisphosphonate analogue potently inhibits farnesyl diphosphate synthase. Diphosphonates 91-105 farnesyl diphosphate synthase Homo sapiens 133-162 31718134-2 2019 In this study, a novel magnetic hydrogel is formed by simply mixing bisphosphonate (BP) modified hyaluronic acid (i.e. HA-BP) polymeric solution and iron oxide (Fe3O4) nanoparticle dispersion, in which the hydrogel networks are crosslinked by BP groups and iron atoms on the surface of particle. Diphosphonates 68-82 hyaluronan binding protein 2 Homo sapiens 119-124 31718134-2 2019 In this study, a novel magnetic hydrogel is formed by simply mixing bisphosphonate (BP) modified hyaluronic acid (i.e. HA-BP) polymeric solution and iron oxide (Fe3O4) nanoparticle dispersion, in which the hydrogel networks are crosslinked by BP groups and iron atoms on the surface of particle. Diphosphonates 84-86 hyaluronan binding protein 2 Homo sapiens 119-124 31821387-5 2019 In case of lung adenocarcinoma bisphosphonate treatment inhibited both wild-type and mutated K-RAS, although tumor cells carrying mutated K-RAS seemed to be more sensitive to the bisphosphonate treatment. Diphosphonates 179-193 KRAS proto-oncogene, GTPase Homo sapiens 138-143 31828096-6 2019 Overall in the pairwise meta-analyses, bisphosphonate use significantly reduced the risk of new vertebral, hip, and nonvertebral nonhip fractures, with ORs and 95% confidence intervals of 0.56 (0.49-0.64), 0.69 (0.48-0.98), and 0.82 (0.70-0.97), respectively. Diphosphonates 39-53 hedgehog interacting protein Homo sapiens 107-110 31300749-7 2019 Osteocalcin levels were greater in people reporting no alcohol consumption compared with drinkers (15.49 ng/ml versus 18.58 ng/ml, p < 0.0002), lower in diabetics compared with nondiabetics (15.23 ng/ml versus 18.92 ng/ml, p = 0.0001), and lower in bisphosphonate users compared with nonusers (15.50 ng/ml versus 18.58 ng/ml, p < 0.03). Diphosphonates 249-263 bone gamma-carboxyglutamate protein Homo sapiens 0-11 31300749-10 2019 CONCLUSIONS: Total osteocalcin levels vary based on health habits, body composition, comorbid illnesses, and bisphosphonate use in men with chronic spinal cord injury. Diphosphonates 109-123 bone gamma-carboxyglutamate protein Homo sapiens 19-30 31324954-11 2019 Accumulation of cleaved caspase-8 in MDA-MB-231 cells on bisphosphonate-treated bone indicated increased apoptosis in the cells. Diphosphonates 57-71 caspase 8 Homo sapiens 24-33 31773111-2 2019 We present a case of a bisphosphonate-associated peri-implant atypical femur fracture following use of a recon nail for treatment of a prior bisphosphonate-associated atypical femur fracture. Diphosphonates 23-37 perilipin 1 Homo sapiens 49-53 31773111-2 2019 We present a case of a bisphosphonate-associated peri-implant atypical femur fracture following use of a recon nail for treatment of a prior bisphosphonate-associated atypical femur fracture. Diphosphonates 141-155 perilipin 1 Homo sapiens 49-53 31772574-9 2019 Furthermore, immunostaining for podocyte injury markers revealed that both desmin- and connexin43-positive areas were smaller in the risedronate-treated group than in the untreated group, suggesting that bisphosphonates could rescue Pi-induced podocyte injury. Diphosphonates 204-219 gap junction protein, alpha 1 Rattus norvegicus 87-97 31400171-4 2019 The aim of the study was to investigate the impacts of PRP and PRF on adhesion of bisphosphonate-pretreated osteoblasts on titanium implant surfaces using the cell-count wash assay, the MTT-assay as well as real-time-cell analyser assay and scanning electronic microscopy. Diphosphonates 82-96 prion protein Homo sapiens 55-58 31400171-12 2019 Therefore, PRP and PRF may improve initial bone apposition and primary healing of dental implants in patients with bisphosphonate treatment. Diphosphonates 115-129 prion protein Homo sapiens 11-14 31612052-10 2019 The present study demonstrated that among the patients who received TKIs (EGFR TKIs or ALK TKIs), those who also received Bps experienced significantly longer PFS time and tended to exhibit significantly improved BM-OS time, which indicated that Bps should be added to the treatment regimen of patients with NSCLC exhibiting genetic mutations and bone metastasis who have been prescribed TKIs (EGFR TKIs or ALK TKIs). Diphosphonates 122-125 epidermal growth factor receptor Homo sapiens 74-78 31612052-10 2019 The present study demonstrated that among the patients who received TKIs (EGFR TKIs or ALK TKIs), those who also received Bps experienced significantly longer PFS time and tended to exhibit significantly improved BM-OS time, which indicated that Bps should be added to the treatment regimen of patients with NSCLC exhibiting genetic mutations and bone metastasis who have been prescribed TKIs (EGFR TKIs or ALK TKIs). Diphosphonates 122-125 ALK receptor tyrosine kinase Homo sapiens 87-90 31612052-10 2019 The present study demonstrated that among the patients who received TKIs (EGFR TKIs or ALK TKIs), those who also received Bps experienced significantly longer PFS time and tended to exhibit significantly improved BM-OS time, which indicated that Bps should be added to the treatment regimen of patients with NSCLC exhibiting genetic mutations and bone metastasis who have been prescribed TKIs (EGFR TKIs or ALK TKIs). Diphosphonates 122-125 epidermal growth factor receptor Homo sapiens 394-398 31612052-10 2019 The present study demonstrated that among the patients who received TKIs (EGFR TKIs or ALK TKIs), those who also received Bps experienced significantly longer PFS time and tended to exhibit significantly improved BM-OS time, which indicated that Bps should be added to the treatment regimen of patients with NSCLC exhibiting genetic mutations and bone metastasis who have been prescribed TKIs (EGFR TKIs or ALK TKIs). Diphosphonates 122-125 ALK receptor tyrosine kinase Homo sapiens 407-410 31612052-10 2019 The present study demonstrated that among the patients who received TKIs (EGFR TKIs or ALK TKIs), those who also received Bps experienced significantly longer PFS time and tended to exhibit significantly improved BM-OS time, which indicated that Bps should be added to the treatment regimen of patients with NSCLC exhibiting genetic mutations and bone metastasis who have been prescribed TKIs (EGFR TKIs or ALK TKIs). Diphosphonates 246-249 epidermal growth factor receptor Homo sapiens 74-78 31612052-10 2019 The present study demonstrated that among the patients who received TKIs (EGFR TKIs or ALK TKIs), those who also received Bps experienced significantly longer PFS time and tended to exhibit significantly improved BM-OS time, which indicated that Bps should be added to the treatment regimen of patients with NSCLC exhibiting genetic mutations and bone metastasis who have been prescribed TKIs (EGFR TKIs or ALK TKIs). Diphosphonates 246-249 ALK receptor tyrosine kinase Homo sapiens 87-90 31612052-10 2019 The present study demonstrated that among the patients who received TKIs (EGFR TKIs or ALK TKIs), those who also received Bps experienced significantly longer PFS time and tended to exhibit significantly improved BM-OS time, which indicated that Bps should be added to the treatment regimen of patients with NSCLC exhibiting genetic mutations and bone metastasis who have been prescribed TKIs (EGFR TKIs or ALK TKIs). Diphosphonates 246-249 epidermal growth factor receptor Homo sapiens 394-398 31612052-10 2019 The present study demonstrated that among the patients who received TKIs (EGFR TKIs or ALK TKIs), those who also received Bps experienced significantly longer PFS time and tended to exhibit significantly improved BM-OS time, which indicated that Bps should be added to the treatment regimen of patients with NSCLC exhibiting genetic mutations and bone metastasis who have been prescribed TKIs (EGFR TKIs or ALK TKIs). Diphosphonates 246-249 ALK receptor tyrosine kinase Homo sapiens 407-410 30949254-2 2019 Osteonecrosis of the jaw similar to that occurring with BPs is also produced with the anti-receptor activator of nuclear factor kappa-Beta ligand (RANKL) antibody denosumab, a bone resorption inhibitor that has a different mode of action from BPs, and there is also a report of osteonecrosis of the jaw related to bevacizumab, an angiogenic inhibitor. Diphosphonates 56-59 TNF superfamily member 11 Homo sapiens 86-145 30949254-2 2019 Osteonecrosis of the jaw similar to that occurring with BPs is also produced with the anti-receptor activator of nuclear factor kappa-Beta ligand (RANKL) antibody denosumab, a bone resorption inhibitor that has a different mode of action from BPs, and there is also a report of osteonecrosis of the jaw related to bevacizumab, an angiogenic inhibitor. Diphosphonates 56-59 TNF superfamily member 11 Homo sapiens 147-152 30949254-2 2019 Osteonecrosis of the jaw similar to that occurring with BPs is also produced with the anti-receptor activator of nuclear factor kappa-Beta ligand (RANKL) antibody denosumab, a bone resorption inhibitor that has a different mode of action from BPs, and there is also a report of osteonecrosis of the jaw related to bevacizumab, an angiogenic inhibitor. Diphosphonates 243-246 TNF superfamily member 11 Homo sapiens 86-145 30949254-2 2019 Osteonecrosis of the jaw similar to that occurring with BPs is also produced with the anti-receptor activator of nuclear factor kappa-Beta ligand (RANKL) antibody denosumab, a bone resorption inhibitor that has a different mode of action from BPs, and there is also a report of osteonecrosis of the jaw related to bevacizumab, an angiogenic inhibitor. Diphosphonates 243-246 TNF superfamily member 11 Homo sapiens 147-152 31427399-0 2019 Metal coordination is crucial for GGPPS-bisphosphonates interactions: A crystallographic and computational analysis. Diphosphonates 40-55 geranylgeranyl diphosphate synthase 1 Homo sapiens 34-39 31427399-3 2019 Most available GGPPS inhibitors are bisphosphonates, but the clinically available compounds demonstrate poor pharmacokinetic properties. Diphosphonates 36-51 geranylgeranyl diphosphate synthase 1 Homo sapiens 15-20 31427399-6 2019 Here, we report the 2.2 A crystal structure of hGGPPS in complex with ibandronate, clearly depicting the involvement of three Mg2+ ions in bisphosphonate-protein interactions. Diphosphonates 139-153 geranylgeranyl diphosphate synthase 1 Homo sapiens 47-53 31427399-9 2019 SIGNIFICANCE STATEMENT: Bisphosphonates are inhibitors of GGPPS, a metalloenzyme crucial for cell survival. Diphosphonates 24-39 geranylgeranyl diphosphate synthase 1 Homo sapiens 58-63 31423185-7 2019 It was also identified that BPs modulated Ras-related C3 botulinum toxin substrate 1, Ras homolog gene family member A and cell division control protein 42 homolog gene expression. Diphosphonates 28-31 Rac family small GTPase 1 Homo sapiens 42-84 31256803-1 2019 BACKGROUND: The authors" aim in this systematic review was to evaluate the validity of using preoperative serum C-terminal cross-linking telopeptide (CTX) levels as a predictive factor of increased risk of developing medication-related osteonecrosis of the jaw (MRONJ) in patients receiving bisphosphonate (BP) therapy who underwent invasive dental procedures. Diphosphonates 291-305 cytochrome P450 family 27 subfamily A member 1 Homo sapiens 150-153 31256803-1 2019 BACKGROUND: The authors" aim in this systematic review was to evaluate the validity of using preoperative serum C-terminal cross-linking telopeptide (CTX) levels as a predictive factor of increased risk of developing medication-related osteonecrosis of the jaw (MRONJ) in patients receiving bisphosphonate (BP) therapy who underwent invasive dental procedures. Diphosphonates 307-309 cytochrome P450 family 27 subfamily A member 1 Homo sapiens 150-153 31256803-7 2019 The average serum CTX level in patients who received BP before surgery was 198.25 picograms per milliliter. Diphosphonates 53-55 cytochrome P450 family 27 subfamily A member 1 Homo sapiens 18-21 31560533-4 2019 In the present study we employed a diphosphonate containing a protonated amine, 1-ammoniummethylenediphosphonate [NH3CH(PO3)23-; (Hamdp)], as the ligand to construct paddlewheel Ru2(Hamdp)2 building block. Diphosphonates 35-48 doublecortin domain containing 2 Homo sapiens 178-181 31260659-12 2019 SIGNIFICANT STATEMENTS: The present study establishes that in mice the RANKL signaling activity level is a major modulator of the effects and side-effects of bisphosphonates on the individual skeleton during growth. Diphosphonates 158-173 tumor necrosis factor (ligand) superfamily, member 11 Mus musculus 71-76 31462380-0 2019 miR-101-3p/Rap1b signal pathway plays a key role in osteoclast differentiation after treatment with bisphosphonates. Diphosphonates 100-115 RAS related protein 1b Mus musculus 11-16 31462380-3 2019 The objective of this study was to determine the role of miR-101-3p/Rap1b signal pathway in osteoclast differentiation after treatment with bisphosphonates. Diphosphonates 140-155 RAS related protein 1b Mus musculus 68-73 31462380-12 2019 Taken together, our data demonstrate that miR-101-3p/Rap1b signal pathway plays a key role in osteoclast differentiation after treatment with bisphosphonates. Diphosphonates 142-157 RAS related protein 1b Mus musculus 53-58 30712064-0 2019 Novel bisphosphonate compound FYB-931 preferentially inhibits aortic calcification in vitamin D3-treated rats. Diphosphonates 6-20 FYN binding protein 1 Rattus norvegicus 30-33 31423185-8 2019 Consistent with the observed growth inhibitory effects, BPs also inhibited the cell cycle by promoting G1 phase arrest and the downregulation of cyclin D1 and upregulation of p21. Diphosphonates 56-59 cyclin D1 Homo sapiens 145-154 31423185-8 2019 Consistent with the observed growth inhibitory effects, BPs also inhibited the cell cycle by promoting G1 phase arrest and the downregulation of cyclin D1 and upregulation of p21. Diphosphonates 56-59 H3 histone pseudogene 16 Homo sapiens 175-178 31423185-9 2019 Additionally, BPs were revealed to induce reactive oxygen species expression, caspase-3 activity and increase the mitochondrial transmembrane potential, which was associated with apoptosis. Diphosphonates 14-17 caspase 3 Homo sapiens 78-87 31423185-10 2019 BP-induced cancer cell apoptosis was detected by acridine orange/ethidium bromide staining and flow cytometry analysis, and was identified to be associated with the induction of caspase-3 and cytochrome c protein expression. Diphosphonates 0-2 caspase 3 Homo sapiens 178-187 31423185-10 2019 BP-induced cancer cell apoptosis was detected by acridine orange/ethidium bromide staining and flow cytometry analysis, and was identified to be associated with the induction of caspase-3 and cytochrome c protein expression. Diphosphonates 0-2 cytochrome c, somatic Homo sapiens 192-204 31423185-11 2019 Furthermore, BPs significantly decreased cancer cell migration in a dose-dependent manner and reduced matrix metallopeptidase-9 protein expression. Diphosphonates 13-16 matrix metallopeptidase 9 Homo sapiens 102-127 31023104-2 2019 The nitrogen-containing BPs (NBPs) target osteoclast activity by disrupting protein prenylation via inhibition of farnesyl diphosphate synthase (FDPS). Diphosphonates 24-27 farnesyl diphosphate synthase Homo sapiens 114-143 31196208-0 2019 Adipose-derived stem cells prevent the onset of bisphosphonate-related osteonecrosis of the jaw through transforming growth factor beta-1-mediated gingival wound healing. Diphosphonates 48-62 potassium calcium-activated channel subfamily M regulatory beta subunit 1 Homo sapiens 131-137 31269114-1 2019 The present study aimed to investigate the use of platelet-rich plasma (PRP) on tooth extraction sites in rats treated with bisphosphonates. Diphosphonates 124-139 proline rich protein 2-like 1 Rattus norvegicus 72-75 31256304-12 2019 RESULTS: Serum CTX level was dramatically decreased in the long-term BPs user group (p < 0.05). Diphosphonates 69-72 cytochrome P450 family 27 subfamily A member 1 Homo sapiens 15-18 31165745-13 2019 This study demonstrates that treatment with PRF/PRP may have positive effects in the therapy of Bisphosphonate-Related Osteonecrosis of the Jaw (BRONJ). Diphosphonates 96-110 prion protein Homo sapiens 48-51 31023104-2 2019 The nitrogen-containing BPs (NBPs) target osteoclast activity by disrupting protein prenylation via inhibition of farnesyl diphosphate synthase (FDPS). Diphosphonates 24-27 farnesyl diphosphate synthase Homo sapiens 145-149 30948499-12 2019 Bisphosphonates were effective to this extremely rare OI induced by P4HB mutation. Diphosphonates 0-15 prolyl 4-hydroxylase subunit beta Homo sapiens 68-72 30909508-4 2019 Zoledronate, a nitrogen-containing bisphosphonate, markedly increased both the receptor activator of nuclear factor kB ligand (RANKL) as well as sclerostin in osteocyte-like MLO-Y4 cells, which were functionally revalidated by osteoclast/osteoblast generating activities of the conditioned medium obtained from zoledronate-treated MLO-Y4 cells. Diphosphonates 35-49 tumor necrosis factor (ligand) superfamily, member 11 Mus musculus 79-125 30979900-2 2019 Herein, we employ bisphosphonate (BP)-coated gold nanoparticle template (BNP) to direct the swift and convertible formation of Mg2+-functional Mg2+-BP nanoparticle (NP) on the BP-AuNP surface via reversible Mg2+-BP coordination, thus producing (Mg2+-BP)-Au dimer (MgBNP). Diphosphonates 18-32 natriuretic peptide B Homo sapiens 73-76 30979900-2 2019 Herein, we employ bisphosphonate (BP)-coated gold nanoparticle template (BNP) to direct the swift and convertible formation of Mg2+-functional Mg2+-BP nanoparticle (NP) on the BP-AuNP surface via reversible Mg2+-BP coordination, thus producing (Mg2+-BP)-Au dimer (MgBNP). Diphosphonates 34-36 natriuretic peptide B Homo sapiens 73-76 30616028-9 2019 In conclusion, periostin may be a biochemical marker indicative of the most severe forms of FD and could be used to monitor patients treated with bisphosphonates. Diphosphonates 146-161 periostin Homo sapiens 15-24 30624969-0 2019 Zoledronic acid promotes TLR-4-mediated M1 macrophage polarization in bisphosphonate-related osteonecrosis of the jaw. Diphosphonates 70-84 toll-like receptor 4 Mus musculus 25-30 30624969-7 2019 Taken together, our findings suggest that TLR-4-mediated macrophage polarization participates in the pathogenesis of BRONJ in mice, and TLR-4 may be a potential target for the prevention and therapeutic treatment of BRONJ.-Zhu, W., Xu, R., Du, J., Fu, Y., Li, S., Zhang, P., Liu, L., Jiang, H. Zoledronic acid promotes TLR-4-mediated M1 macrophage polarization in bisphosphonate-related osteonecrosis of the jaw. Diphosphonates 364-378 toll-like receptor 4 Mus musculus 42-47 30624969-7 2019 Taken together, our findings suggest that TLR-4-mediated macrophage polarization participates in the pathogenesis of BRONJ in mice, and TLR-4 may be a potential target for the prevention and therapeutic treatment of BRONJ.-Zhu, W., Xu, R., Du, J., Fu, Y., Li, S., Zhang, P., Liu, L., Jiang, H. Zoledronic acid promotes TLR-4-mediated M1 macrophage polarization in bisphosphonate-related osteonecrosis of the jaw. Diphosphonates 364-378 toll-like receptor 4 Mus musculus 136-141 30624969-7 2019 Taken together, our findings suggest that TLR-4-mediated macrophage polarization participates in the pathogenesis of BRONJ in mice, and TLR-4 may be a potential target for the prevention and therapeutic treatment of BRONJ.-Zhu, W., Xu, R., Du, J., Fu, Y., Li, S., Zhang, P., Liu, L., Jiang, H. Zoledronic acid promotes TLR-4-mediated M1 macrophage polarization in bisphosphonate-related osteonecrosis of the jaw. Diphosphonates 364-378 toll-like receptor 4 Mus musculus 136-141 30909508-4 2019 Zoledronate, a nitrogen-containing bisphosphonate, markedly increased both the receptor activator of nuclear factor kB ligand (RANKL) as well as sclerostin in osteocyte-like MLO-Y4 cells, which were functionally revalidated by osteoclast/osteoblast generating activities of the conditioned medium obtained from zoledronate-treated MLO-Y4 cells. Diphosphonates 35-49 tumor necrosis factor (ligand) superfamily, member 11 Mus musculus 127-132 30913006-11 2019 Furthermore, bisphosphonates exerted beneficial effects on proband 1, who carried the WNT1 mutations, by increasing bone mineral density Z-score, reshaping the compressed vertebrae and decreasing the fracture risk. Diphosphonates 13-28 Wnt family member 1 Homo sapiens 86-90 30036888-0 2019 QSAR Models for Nitrogen Containing Monophosphonate and Bisphosphonate Derivatives as Human Farnesyl Pyrophosphate Synthase Inhibitors Based on Monte Carlo Method. Diphosphonates 56-70 farnesyl diphosphate synthase Homo sapiens 92-123 30832685-0 2019 Osteoclastic expression of higher-level regulators NFATc1 and BCL6 in medication-related osteonecrosis of the jaw secondary to bisphosphonate therapy: a comparison with osteoradionecrosis and osteomyelitis. Diphosphonates 127-141 nuclear factor of activated T cells 1 Homo sapiens 51-57 30832685-0 2019 Osteoclastic expression of higher-level regulators NFATc1 and BCL6 in medication-related osteonecrosis of the jaw secondary to bisphosphonate therapy: a comparison with osteoradionecrosis and osteomyelitis. Diphosphonates 127-141 BCL6 transcription repressor Homo sapiens 62-66 30470573-1 2019 BACKGROUND: HA modified by bisphosphonate (BP) (HA-BP) was synthesized by chemical reaction and possessed promising properties such as self-healing, injection ability, and strong adhesion. Diphosphonates 27-41 hyaluronic acid binding protein 2 Mus musculus 48-53 30342967-6 2019 By increasing the permeability of the nuclear membrane with statin and bisphosphonates, 2 fibroblast cell lines exposed to high-LET particles were shown to be protected by an accelerated ATM nucleo-shuttling. Diphosphonates 71-86 ATM serine/threonine kinase Homo sapiens 187-190 30735554-0 2019 Prevention of tooth extraction-triggered bisphosphonate-related osteonecrosis of the jaws with basic fibroblast growth factor: An experimental study in rats. Diphosphonates 41-55 fibroblast growth factor 2 Rattus norvegicus 95-125 30735554-12 2019 The growth-stimulating effects of bFGF may have offset the inhibition of wound healing by BP. Diphosphonates 90-92 fibroblast growth factor 2 Rattus norvegicus 34-38 30675875-0 2019 Epidermal Growth Factor Reverses the Inhibitory Effects of the Bisphosphonate, Zoledronic Acid, on Human Oral Keratinocytes and Human Vascular Endothelial Cells In Vitro via the Epidermal Growth Factor Receptor (EGFR)/Akt/Phosphoinositide 3-Kinase (PI3K) Signaling Pathway. Diphosphonates 63-77 epidermal growth factor Homo sapiens 0-23 30675875-0 2019 Epidermal Growth Factor Reverses the Inhibitory Effects of the Bisphosphonate, Zoledronic Acid, on Human Oral Keratinocytes and Human Vascular Endothelial Cells In Vitro via the Epidermal Growth Factor Receptor (EGFR)/Akt/Phosphoinositide 3-Kinase (PI3K) Signaling Pathway. Diphosphonates 63-77 epidermal growth factor receptor Homo sapiens 178-210 30675875-0 2019 Epidermal Growth Factor Reverses the Inhibitory Effects of the Bisphosphonate, Zoledronic Acid, on Human Oral Keratinocytes and Human Vascular Endothelial Cells In Vitro via the Epidermal Growth Factor Receptor (EGFR)/Akt/Phosphoinositide 3-Kinase (PI3K) Signaling Pathway. Diphosphonates 63-77 epidermal growth factor receptor Homo sapiens 212-216 30675875-0 2019 Epidermal Growth Factor Reverses the Inhibitory Effects of the Bisphosphonate, Zoledronic Acid, on Human Oral Keratinocytes and Human Vascular Endothelial Cells In Vitro via the Epidermal Growth Factor Receptor (EGFR)/Akt/Phosphoinositide 3-Kinase (PI3K) Signaling Pathway. Diphosphonates 63-77 AKT serine/threonine kinase 1 Homo sapiens 218-221 30675875-0 2019 Epidermal Growth Factor Reverses the Inhibitory Effects of the Bisphosphonate, Zoledronic Acid, on Human Oral Keratinocytes and Human Vascular Endothelial Cells In Vitro via the Epidermal Growth Factor Receptor (EGFR)/Akt/Phosphoinositide 3-Kinase (PI3K) Signaling Pathway. Diphosphonates 63-77 phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta Homo sapiens 222-247 30675875-2 2019 The aims of this study were to evaluate the effects of treatment with the bisphosphonate, zoledronic acid, on human oral keratinocytes (HOKs) and human umbilical vein endothelial cells (HUVECs) in vitro, and whether epidermal growth factor (EGF) could alter these effects. Diphosphonates 74-88 epidermal growth factor Homo sapiens 216-239 30675875-2 2019 The aims of this study were to evaluate the effects of treatment with the bisphosphonate, zoledronic acid, on human oral keratinocytes (HOKs) and human umbilical vein endothelial cells (HUVECs) in vitro, and whether epidermal growth factor (EGF) could alter these effects. Diphosphonates 74-88 epidermal growth factor Homo sapiens 241-244 30675875-10 2019 CONCLUSIONS EGF partially reversed the effects of the bisphosphonate, zoledronic acid, on HOKs and HUVECs in vitro via the EGFR/Akt/PI3K signaling pathway. Diphosphonates 54-68 epidermal growth factor Homo sapiens 12-15 30675875-10 2019 CONCLUSIONS EGF partially reversed the effects of the bisphosphonate, zoledronic acid, on HOKs and HUVECs in vitro via the EGFR/Akt/PI3K signaling pathway. Diphosphonates 54-68 epidermal growth factor receptor Homo sapiens 123-127 30675875-10 2019 CONCLUSIONS EGF partially reversed the effects of the bisphosphonate, zoledronic acid, on HOKs and HUVECs in vitro via the EGFR/Akt/PI3K signaling pathway. Diphosphonates 54-68 AKT serine/threonine kinase 1 Homo sapiens 128-131 31131341-11 2019 Logistic regression modeling predicted that with BPN exposure, a 1-year increase in age would be associated with an 8.2% decrease in fracture probability for preadolescent individuals with OI-1, compared with no decrease in individuals who had never received any BPN (p < 0.05). Diphosphonates 49-52 collagen type I alpha 1 chain Homo sapiens 189-193 30470573-1 2019 BACKGROUND: HA modified by bisphosphonate (BP) (HA-BP) was synthesized by chemical reaction and possessed promising properties such as self-healing, injection ability, and strong adhesion. Diphosphonates 43-45 hyaluronic acid binding protein 2 Mus musculus 48-53 31155589-7 2019 These results, together with previous ones, suggest that (a) pro-IL-1beta and pro-IL-18 accumulate within cells in soft-tissues exposed to N-BPs, and infection may augment not only their production, but also the release of their mature forms, (b) IL-1beta and IL-18 (possibly together with TNF-alpha) may play important roles in N-BP-induced inflammation and/or necrosis, and (c) mechanisms underlying the cytotoxic effects of BPs may differ between N-BPs and non-N-BPs. Diphosphonates 141-144 interleukin 1 beta Mus musculus 65-73 31155589-7 2019 These results, together with previous ones, suggest that (a) pro-IL-1beta and pro-IL-18 accumulate within cells in soft-tissues exposed to N-BPs, and infection may augment not only their production, but also the release of their mature forms, (b) IL-1beta and IL-18 (possibly together with TNF-alpha) may play important roles in N-BP-induced inflammation and/or necrosis, and (c) mechanisms underlying the cytotoxic effects of BPs may differ between N-BPs and non-N-BPs. Diphosphonates 141-144 interleukin 18 Mus musculus 82-87 30383490-6 2019 RESULTS: Within the first year of therapy with BPs, the level of alkaline phosphatase (ALP) decreased by 30.3% of baseline in the alendronate cases and by 22.7 +- 16.9% and 34.1 +- 26.3% in the pamidronate (PAM) (n = 10) and zoledronic acid (ZA) (n = 11) groups, respectively. Diphosphonates 47-50 alkaline phosphatase, placental Homo sapiens 65-85 31016165-1 2019 Background: Traditionally, bisphosphonates are used to treat active Paget"s disease of bone (PDB). Diphosphonates 27-42 PDB1 Homo sapiens 93-96 29932001-0 2019 Locally administered bisphosphonate in hip stem revisions using the bone impaction grafting technique: a randomised, placebo-controlled study with DXA and five-year RSA follow-up. Diphosphonates 21-35 hedgehog interacting protein Homo sapiens 39-42 30383490-6 2019 RESULTS: Within the first year of therapy with BPs, the level of alkaline phosphatase (ALP) decreased by 30.3% of baseline in the alendronate cases and by 22.7 +- 16.9% and 34.1 +- 26.3% in the pamidronate (PAM) (n = 10) and zoledronic acid (ZA) (n = 11) groups, respectively. Diphosphonates 47-50 alkaline phosphatase, placental Homo sapiens 87-90 30383490-9 2019 Number of affected bones was positively correlated with baseline serum ALP levels ( r = 0.533; P = .011), which was the only significant factor affecting efficacy of BPs. Diphosphonates 166-169 alkaline phosphatase, placental Homo sapiens 71-74 30216659-2 2018 The aim of this study was to investigate the regulation of IL-33 by 3-hydroxy-3-methylglutaryl-coenzyme-A (HMG-CoA) reductase inhibitors (statins) and bisphosphonates (BPs) in human cardiac tissue. Diphosphonates 151-166 interleukin 33 Homo sapiens 59-64 30636879-10 2019 Zoledronate (ROR: 319.3, 95% CI: 296.0-344.4) had the highest ROR among BP agents. Diphosphonates 72-74 long intergenic non-protein coding RNA, regulator of reprogramming Homo sapiens 13-16 30636879-10 2019 Zoledronate (ROR: 319.3, 95% CI: 296.0-344.4) had the highest ROR among BP agents. Diphosphonates 72-74 long intergenic non-protein coding RNA, regulator of reprogramming Homo sapiens 62-65 30216659-2 2018 The aim of this study was to investigate the regulation of IL-33 by 3-hydroxy-3-methylglutaryl-coenzyme-A (HMG-CoA) reductase inhibitors (statins) and bisphosphonates (BPs) in human cardiac tissue. Diphosphonates 168-171 interleukin 33 Homo sapiens 59-64 30216659-8 2018 As IL-33 was previously shown to exert cardioprotective effects, one could speculate that such up-regulation of IL-33 expression in human cardiac cells, which might happen mainly through protein geranylgeranylation, could be a novel mechanism contributing to known cardioprotective effects of statins and BPs. Diphosphonates 305-308 interleukin 33 Homo sapiens 3-8 30216659-8 2018 As IL-33 was previously shown to exert cardioprotective effects, one could speculate that such up-regulation of IL-33 expression in human cardiac cells, which might happen mainly through protein geranylgeranylation, could be a novel mechanism contributing to known cardioprotective effects of statins and BPs. Diphosphonates 305-308 interleukin 33 Homo sapiens 112-117 30275041-0 2018 Reduced Activity of Geranylgeranyl Diphosphate Synthase Mutant Is Involved in Bisphosphonate-Induced Atypical Fractures. Diphosphonates 78-92 geranylgeranyl diphosphate synthase 1 Homo sapiens 20-55 30637239-0 2018 Combined effect of recombinant human bone morphogenetic protein-2 and low level laser irradiation on bisphosphonate-treated osteoblasts. Diphosphonates 101-115 bone morphogenetic protein 2 Homo sapiens 37-65 30637239-1 2018 Objectives: The purpose of this study was to evaluate the synergic effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) and low-level laser therapy (LLLT) on bisphosphonate-treated osteoblasts. Diphosphonates 172-186 bone morphogenetic protein 2 Homo sapiens 95-123 30275041-3 2018 Recently, a novel missense mutation (D188Y) in the GGPS1 gene, encoding for geranylgeranyl diphosphate synthase (GGPPS), was associated with bisphosphonate-induced atypical fractures. Diphosphonates 141-155 geranylgeranyl diphosphate synthase 1 Homo sapiens 51-56 30275041-3 2018 Recently, a novel missense mutation (D188Y) in the GGPS1 gene, encoding for geranylgeranyl diphosphate synthase (GGPPS), was associated with bisphosphonate-induced atypical fractures. Diphosphonates 141-155 geranylgeranyl diphosphate synthase 1 Homo sapiens 76-111 30275041-3 2018 Recently, a novel missense mutation (D188Y) in the GGPS1 gene, encoding for geranylgeranyl diphosphate synthase (GGPPS), was associated with bisphosphonate-induced atypical fractures. Diphosphonates 141-155 geranylgeranyl diphosphate synthase 1 Homo sapiens 113-118 30275041-8 2018 In agreement, we show that GGPPS-D188Y exhibits ~3-fold reduction in the binding affinity of zoledronate, a commonly used bisphosphonate. Diphosphonates 122-136 geranylgeranyl diphosphate synthase 1 Homo sapiens 27-32 30275041-10 2018 Finally, we determined the crystal structure of zoledronate-bound GGPPS-D188Y, revealing large ligand-induced binding pocket rearrangements, revising the previous model for GGPPS-bisphosphonate interactions. Diphosphonates 179-193 geranylgeranyl diphosphate synthase 1 Homo sapiens 66-71 30275041-10 2018 Finally, we determined the crystal structure of zoledronate-bound GGPPS-D188Y, revealing large ligand-induced binding pocket rearrangements, revising the previous model for GGPPS-bisphosphonate interactions. Diphosphonates 179-193 geranylgeranyl diphosphate synthase 1 Homo sapiens 173-178 30275041-12 2018 However, under bisphosphonate treatment, GGPPS activity is reduced below a crucial threshold for osteoclast function, leading to impaired bone remodeling and increased susceptibility to atypical fractures. Diphosphonates 15-29 geranylgeranyl diphosphate synthase 1 Homo sapiens 41-46 30359515-6 2018 Owning to the function of bisphosphonates as clinical drugs to deplete TAMs, suppressed angiogenesis, normalized tumor vasculatures, enhanced intratumoral perfusion, and relieved tumor hypoxia are observed after TAM depletion induced by CaBP-PEG. Diphosphonates 26-41 S100 calcium binding protein G Homo sapiens 237-241 30388448-3 2018 report that lipophilic statins or biphosphonates, targeting the mevalonate pathway, act as efficient vaccine adjuvants and synergize with anti-PD1 against cancer. Diphosphonates 34-48 programmed cell death 1 Homo sapiens 143-146 30096489-4 2018 Bisphosphonates (BPs), referred to as gold standard for osteoporosis treatment, have well established role in attenuation of bone resorption and osteoclast apoptosis by inhibition of farnesyl pyrophosphate synthase enzyme (FPPS) in mevalonate pathway. Diphosphonates 0-15 farnesyl diphosphate synthase Homo sapiens 183-214 30431005-7 2018 CONCLUSIONS: HU mice appear to be a useful model for immobility-induced osteoporotic pain and hindlimb-unloading-induced bone loss, as well as upregulation of CGRP and TRPV1 expressions in DRG neurons, and BP treatment prevented bone loss and mechanical hyperalgesia. Diphosphonates 206-208 calcitonin/calcitonin-related polypeptide, alpha Mus musculus 159-163 30206659-0 2018 Bisphosphonate therapy in an infant with generalized arterial calcification with an ABCC6 mutation. Diphosphonates 0-14 ATP binding cassette subfamily C member 6 Homo sapiens 84-89 30206659-2 2018 Bisphosphonate treatment has been described to improve survival in ENPP1-positive GACI patients, but few studies have described bisphosphonate treatment in ABCC6-positive patients. Diphosphonates 0-14 ectonucleotide pyrophosphatase/phosphodiesterase 1 Homo sapiens 67-72 30206659-2 2018 Bisphosphonate treatment has been described to improve survival in ENPP1-positive GACI patients, but few studies have described bisphosphonate treatment in ABCC6-positive patients. Diphosphonates 128-142 ATP binding cassette subfamily C member 6 Homo sapiens 156-161 30206659-13 2018 Aggressive bisphosphonate therapy should be started as soon as possible in patients with infantile arterial calcinosis due to ABCC6 or ENPP1 mutations. Diphosphonates 11-25 ATP binding cassette subfamily C member 6 Homo sapiens 126-131 30206659-13 2018 Aggressive bisphosphonate therapy should be started as soon as possible in patients with infantile arterial calcinosis due to ABCC6 or ENPP1 mutations. Diphosphonates 11-25 ectonucleotide pyrophosphatase/phosphodiesterase 1 Homo sapiens 135-140 30216851-7 2018 Docking calculations were performed identifying putative interactions between some representative novel bisphosphonates and both hFPPS and hGGPPS. Diphosphonates 104-119 geranylgeranyl diphosphate synthase 1 Homo sapiens 139-145 30222658-4 2018 RECENT FINDINGS: Medication-induced uveitis has become particularly important and more frequently seen because of the advent of biologic therapies such as immune checkpoint inhibitors (ICPIs), BRAF, and MEK inhibitors, antivascular endothelial growth factor agents, and antitumor necrosis factor agents, as well as newer systemic bisphosphonates are strongly associated with uveitis. Diphosphonates 330-345 mitogen-activated protein kinase kinase 7 Homo sapiens 203-206 30096489-4 2018 Bisphosphonates (BPs), referred to as gold standard for osteoporosis treatment, have well established role in attenuation of bone resorption and osteoclast apoptosis by inhibition of farnesyl pyrophosphate synthase enzyme (FPPS) in mevalonate pathway. Diphosphonates 0-15 farnesyl diphosphate synthase Homo sapiens 223-227 30096489-4 2018 Bisphosphonates (BPs), referred to as gold standard for osteoporosis treatment, have well established role in attenuation of bone resorption and osteoclast apoptosis by inhibition of farnesyl pyrophosphate synthase enzyme (FPPS) in mevalonate pathway. Diphosphonates 17-20 farnesyl diphosphate synthase Homo sapiens 183-214 30096489-4 2018 Bisphosphonates (BPs), referred to as gold standard for osteoporosis treatment, have well established role in attenuation of bone resorption and osteoclast apoptosis by inhibition of farnesyl pyrophosphate synthase enzyme (FPPS) in mevalonate pathway. Diphosphonates 17-20 farnesyl diphosphate synthase Homo sapiens 223-227 30378328-6 2018 Compared with the control group and high glucose with bisphosphonates group, the mRNA [CM(155mm]expressions of Beclin1 and LC3 and protein expressions of Beclin1 and LC3II in the high glucose group were increased (P<0.01 or P<0.05). Diphosphonates 54-69 beclin 1 Rattus norvegicus 111-118 30176535-0 2018 CD73 inhibition by purine cytotoxic nucleoside analogue-based diphosphonates. Diphosphonates 62-76 5'-nucleotidase ecto Homo sapiens 0-4 32002964-4 2018 Bisphosphonates (BPs), referred to as gold standard for osteoporosis treatment, have well established role in attenuation of bone resorption and osteoclast apoptosis by inhibition of farnesyl pyrophosphate synthase enzyme (FPPS) in mevalonate pathway. Diphosphonates 0-15 farnesyl diphosphate synthase Homo sapiens 183-214 32002964-4 2018 Bisphosphonates (BPs), referred to as gold standard for osteoporosis treatment, have well established role in attenuation of bone resorption and osteoclast apoptosis by inhibition of farnesyl pyrophosphate synthase enzyme (FPPS) in mevalonate pathway. Diphosphonates 0-15 farnesyl diphosphate synthase Homo sapiens 223-227 32002964-4 2018 Bisphosphonates (BPs), referred to as gold standard for osteoporosis treatment, have well established role in attenuation of bone resorption and osteoclast apoptosis by inhibition of farnesyl pyrophosphate synthase enzyme (FPPS) in mevalonate pathway. Diphosphonates 17-20 farnesyl diphosphate synthase Homo sapiens 183-214 32002964-4 2018 Bisphosphonates (BPs), referred to as gold standard for osteoporosis treatment, have well established role in attenuation of bone resorption and osteoclast apoptosis by inhibition of farnesyl pyrophosphate synthase enzyme (FPPS) in mevalonate pathway. Diphosphonates 17-20 farnesyl diphosphate synthase Homo sapiens 223-227 30378328-6 2018 Compared with the control group and high glucose with bisphosphonates group, the mRNA [CM(155mm]expressions of Beclin1 and LC3 and protein expressions of Beclin1 and LC3II in the high glucose group were increased (P<0.01 or P<0.05). Diphosphonates 54-69 beclin 1 Rattus norvegicus 154-161 30378328-8 2018 CONCLUSION: Bisphosphonates may play a role of down-regulating the expression of Beclin1 and LC3II induced by high-glucose in BMSCs. Diphosphonates 12-27 beclin 1 Rattus norvegicus 81-88 30063094-10 2018 Our study presents the clinical features of the first Asian patient, supports metaphyseal scleroses and fractures as radiological clues, strengthens early bisphosphonate administration, and confirms the etiologic role of the c.1178A>G variant in P4HB across populations. Diphosphonates 155-169 prolyl 4-hydroxylase subunit beta Homo sapiens 249-253 30131657-9 2018 The primary medical intervention for the treatment of osteoporosis in PBC remains bisphosphonates though a benefit in terms of fracture reduction has never been shown. Diphosphonates 82-97 dihydrolipoamide S-acetyltransferase Homo sapiens 70-73 30120241-0 2018 Author Correction: Bisphosphonate enhances TRAIL sensitivity to human osteosarcoma cells via death receptor 5 upregulation. Diphosphonates 19-33 TNF superfamily member 10 Homo sapiens 43-48 30120241-0 2018 Author Correction: Bisphosphonate enhances TRAIL sensitivity to human osteosarcoma cells via death receptor 5 upregulation. Diphosphonates 19-33 TNF receptor superfamily member 10b Homo sapiens 93-109 29996364-0 2018 [Changes of distal-less homeobox genes 5 and Msh homeobox 1 in a rat model of bisphosphonate related osteonecrosis of the jaw]. Diphosphonates 78-92 msh homeobox 1 Rattus norvegicus 45-59 29976176-2 2018 Here we present a case report of GACI in a male infant with a new familial mutation of the ENPP1 gene and the clinical outcome after biphosphonates therapy. Diphosphonates 133-147 ectonucleotide pyrophosphatase/phosphodiesterase 1 Homo sapiens 91-96 30687667-0 2018 Peri-implant Atypical Fractures Associated with Bisphosphonates: Should this Clinical Entity be Included in the Definition of Atypical Femoral Fracture? Diphosphonates 48-63 perilipin 1 Homo sapiens 0-4 28723699-18 2018 The correlation found with the intake of bisphosphonates, capable of inhibiting the action of the farnesyl pyrophosphate synthase enzyme, thus influencing coagulation, requires further prospective studies with research of the methylene tetrahydrofolate reductase mutation in patients with OI type III undergoing surgical procedures. Diphosphonates 41-56 farnesyl diphosphate synthase Homo sapiens 98-129 30687667-3 2018 Cases of peri-implant fractures associated with bisphosphonate use suggest the emergence of a new clinical entity because they are not currently covered by the definition of atypical femoral fracture. Diphosphonates 48-62 perilipin 1 Homo sapiens 9-13 30231385-5 2018 We also review the state of the art in treatment of MM bone disease (MMBD) and the role of bisphosphonates and denosumab, a monoclonal antibody that binds and blocks the activity of receptor activator of nuclear factor-kappa B ligand (RANKL), which was recently approved by the U.S. Food and Drug Administration for MMBD. Diphosphonates 91-106 TNF superfamily member 11 Homo sapiens 182-233 29435826-0 2018 Efficacy of bovine lactoferrin in the post-surgical treatment of patients suffering from bisphosphonate-related osteonecrosis of the jaws: an open-label study. Diphosphonates 89-103 lactotransferrin Bos taurus 19-30 29567200-0 2018 The MEK5/ERK5 mitogen-activated protein kinase cascade is an effector pathway of bone-sustaining bisphosphonates that regulates osteogenic differentiation and mineralization. Diphosphonates 97-112 mitogen-activated protein kinase kinase 5 Homo sapiens 4-8 29567200-0 2018 The MEK5/ERK5 mitogen-activated protein kinase cascade is an effector pathway of bone-sustaining bisphosphonates that regulates osteogenic differentiation and mineralization. Diphosphonates 97-112 mitogen-activated protein kinase 7 Homo sapiens 9-13 30050563-0 2018 A Diversified Spectrometric and Molecular Docking Technique to Biophysical Study of Interaction between Bovine Serum Albumin and Sodium Salt of Risedronic Acid, a Bisphosphonate for Skeletal Disorders. Diphosphonates 163-177 albumin Homo sapiens 111-124 29188452-9 2018 BPs decreased the protein levels of the non-canonical Wnt signaling protein Wnt5a and calmodulin-dependent kinase II. Diphosphonates 0-3 Wnt family member 5A Homo sapiens 54-57 29188452-9 2018 BPs decreased the protein levels of the non-canonical Wnt signaling protein Wnt5a and calmodulin-dependent kinase II. Diphosphonates 0-3 Wnt family member 5A Homo sapiens 68-81 29188452-10 2018 Moreover, recombinant human Wnt5a reversed the effects of BPs on osteoblastic and osteoclastic differentiation. Diphosphonates 58-61 Wnt family member 5A Homo sapiens 28-33 29188452-11 2018 CONCLUSION: This study is the first demonstration that BPs exert negative effects on osteoblastic and osteoclastic processes via the non-canonical Wnt pathway in HMSMSCs. Diphosphonates 55-58 Wnt family member 5A Homo sapiens 147-150 28786016-9 2018 A combination of biphosphonates and statins complemented these impairments by facilitating the nucleoshuttling of ATM and increasing the yield of recognized DSB. Diphosphonates 17-31 ATM serine/threonine kinase Homo sapiens 114-117 29080272-1 2018 Nitrogen-containing bisphosphonates (N-BPs) have been used widely to treat various bone diseases by inhibiting the key enzyme farnesyl pyrophosphate synthase (FPPS) in the mevalonate pathway. Diphosphonates 20-35 farnesyl diphosphate synthase Homo sapiens 126-157 30270749-4 2018 It is hypothesized that BPs interfere with biomaterial turnover during BMP-supported repair of defects filled with beta-tricalcium phosphate (betaTCP) ceramics. Diphosphonates 24-27 bone morphogenetic protein 1 Homo sapiens 71-74 28976594-0 2018 Healing in peri-implant gap with BMP-2 and systemic bisphosphonate is dependent on BMP-2 dose-A canine study. Diphosphonates 52-66 bone morphogenetic protein 2 Canis lupus familiaris 83-88 29485861-0 2018 Bisphosphonate-Linked TrkB Agonist: Cochlea-Targeted Delivery of a Neurotrophic Agent as a Strategy for the Treatment of Hearing Loss. Diphosphonates 0-14 neurotrophic receptor tyrosine kinase 2 Homo sapiens 22-26 29485861-8 2018 The results suggest that bisphosphonate-TrkB agonist conjugates have promise as a novel approach to targeted delivery of drugs to treat sensorineural hearing loss. Diphosphonates 25-39 neurotrophic receptor tyrosine kinase 2 Homo sapiens 40-44 29356986-5 2018 Another, with a thoraco-lumbar ABC, experienced progression of neurological dysfunction after one cycle of bisphosphonate and, therefore, required surgical resection and stabilisation. Diphosphonates 107-121 ATP binding cassette subfamily B member 6 (Langereis blood group) Homo sapiens 31-34 29454604-8 2018 Bisphosphonates could result in increase of IL-1beta expression of fibroblasts. Diphosphonates 0-15 interleukin 1 beta Homo sapiens 44-52 29080272-1 2018 Nitrogen-containing bisphosphonates (N-BPs) have been used widely to treat various bone diseases by inhibiting the key enzyme farnesyl pyrophosphate synthase (FPPS) in the mevalonate pathway. Diphosphonates 20-35 farnesyl diphosphate synthase Homo sapiens 159-163 28856724-0 2018 SIRT1/HERC4 Locus Associated With Bisphosphonate-Induced Osteonecrosis of the Jaw: An Exome-Wide Association Analysis. Diphosphonates 34-48 sirtuin 1 Homo sapiens 0-5 29276048-3 2018 Unfortunately, current bisphosphonate drugs that inhibit FPPS and GGPPS enzymes by acting as a diphosphate substrate analog show poor bioavailability and selectivity for PfFPPS/GGPPS. Diphosphonates 23-37 farnesyl diphosphate synthase Homo sapiens 57-61 29276048-3 2018 Unfortunately, current bisphosphonate drugs that inhibit FPPS and GGPPS enzymes by acting as a diphosphate substrate analog show poor bioavailability and selectivity for PfFPPS/GGPPS. Diphosphonates 23-37 geranylgeranyl diphosphate synthase 1 Homo sapiens 66-71 29276048-3 2018 Unfortunately, current bisphosphonate drugs that inhibit FPPS and GGPPS enzymes by acting as a diphosphate substrate analog show poor bioavailability and selectivity for PfFPPS/GGPPS. Diphosphonates 23-37 geranylgeranyl diphosphate synthase 1 Homo sapiens 177-182 29276048-4 2018 We identified a new non-bisphosphonate compound, MMV019313, which is highly selective for PfFPPS/GGPPS and showed no activity against human FPPS or GGPPS. Diphosphonates 24-38 geranylgeranyl diphosphate synthase 1 Homo sapiens 97-102 29276048-4 2018 We identified a new non-bisphosphonate compound, MMV019313, which is highly selective for PfFPPS/GGPPS and showed no activity against human FPPS or GGPPS. Diphosphonates 24-38 farnesyl diphosphate synthase Homo sapiens 92-96 29276048-5 2018 Inhibition of PfFPPS/GGPPS by MMV019313, but not bisphosphonates, was disrupted in an S228T variant, demonstrating that MMV019313 and bisphosphonates have distinct modes of inhibition. Diphosphonates 134-149 geranylgeranyl diphosphate synthase 1 Homo sapiens 21-26 28856724-0 2018 SIRT1/HERC4 Locus Associated With Bisphosphonate-Induced Osteonecrosis of the Jaw: An Exome-Wide Association Analysis. Diphosphonates 34-48 HECT and RLD domain containing E3 ubiquitin protein ligase 4 Homo sapiens 6-11 29263160-11 2018 CONCLUSIONS: We provide additional evidence of P4HB as a cause of a specific form of OI-CCS and expand on response to treatment with bisphosphonates in this rare disorder. Diphosphonates 133-148 prolyl 4-hydroxylase subunit beta Homo sapiens 47-51 30283886-10 2018 A whole-exome sequencing study in 3 sisters with AFFs showed, among 37 shared genetic variants, a p.Asp188Tyr mutation in the GGPS1 gene in the mevalonate pathway, critical to osteoclast function, which is also inhibited by bisphosphonates. Diphosphonates 224-239 geranylgeranyl diphosphate synthase 1 Homo sapiens 126-131 29683099-7 2018 Non-nitrogen containing bisphosphonates inhibit farnesyl diphosphate synthase which produces farnesyl pyrophosphate. Diphosphonates 24-39 farnesyl diphosphate synthase Homo sapiens 48-77 28856724-11 2018 In summary, we identified the SIRT1/HERC4 locus on chromosome 10 to be associated with iv BP-induced ONJ and two promoter SNPs that might be the potential genetic markers for this association. Diphosphonates 90-92 sirtuin 1 Homo sapiens 30-35 28856724-11 2018 In summary, we identified the SIRT1/HERC4 locus on chromosome 10 to be associated with iv BP-induced ONJ and two promoter SNPs that might be the potential genetic markers for this association. Diphosphonates 90-92 HECT and RLD domain containing E3 ubiquitin protein ligase 4 Homo sapiens 36-41 28534161-6 2017 Concentrations of OPG-Ab were related to bone mineral density (BMD) and fracture history using linear and logistic regression models adjusting for age, gender, disease duration and activity, body mass index and bisphosphonate use. Diphosphonates 211-225 TNF receptor superfamily member 11b Homo sapiens 18-24 29278410-17 2017 In absolute terms, bisphosphonates resulted in 16 fewer deaths per 1000 (47 fewer to 21 more).Outcome definition of quality of life and the measurement tools varied greatly across trials and we were unable to extract any quantitative data for meta-analysis.Bisphosphonates probably increased the number of participants affected by nausea (RR 1.19, 95% CI 1.00 to 1.41; P = 0.05; I2 = 0%; 9 trials; 3008 participants; moderate quality evidence). Diphosphonates 19-34 ribonucleotide reductase catalytic subunit M1 Homo sapiens 339-343 29278410-17 2017 In absolute terms, bisphosphonates resulted in 16 fewer deaths per 1000 (47 fewer to 21 more).Outcome definition of quality of life and the measurement tools varied greatly across trials and we were unable to extract any quantitative data for meta-analysis.Bisphosphonates probably increased the number of participants affected by nausea (RR 1.19, 95% CI 1.00 to 1.41; P = 0.05; I2 = 0%; 9 trials; 3008 participants; moderate quality evidence). Diphosphonates 257-272 ribonucleotide reductase catalytic subunit M1 Homo sapiens 339-343 29278410-19 2017 Bisphosphonates probably increased the number of renal adverse events (RR 1.65, 95% CI 1.11 to 2.46; P = 0.01; I2 = 0%; 7 trials; 1794 participants; moderate quality evidence). Diphosphonates 0-15 ribonucleotide reductase catalytic subunit M1 Homo sapiens 71-75 29109842-0 2017 Submental Perforator Flap for Soft-Tissue Reconstruction in Bisphosphonate-Related Osteonecrosis of the Jaws. Diphosphonates 60-74 arachidonate 5-lipoxygenase activating protein Homo sapiens 21-25 29376607-6 2017 A promising treatment option for a mutation in the vitamin D receptor gene is thiazide diuretics in combination with bisphosphonates. Diphosphonates 117-132 vitamin D receptor Homo sapiens 51-69 28725947-4 2017 To date, the use of anti-TNF agents has been proved to be a valid alternative for patients unresponsive to conventional treatments, such as NSAIDs, corticosteroids, DMARDs and biphosphonates. Diphosphonates 176-190 tumor necrosis factor Homo sapiens 25-28 28937990-7 2017 Administration of W9 or risedronate, a bisphosphonate, to OPG-/-mice significantly decreased the osteoclast number in the alveolar bone. Diphosphonates 39-53 tumor necrosis factor receptor superfamily, member 11b (osteoprotegerin) Mus musculus 58-61 28540505-0 2017 Retrospective evaluation of serum CTX levels after denosumab discontinuation in patients with or without prior exposure to bisphosphonates. Diphosphonates 123-138 cytochrome P450 family 27 subfamily A member 1 Homo sapiens 34-37 28713904-0 2017 Bisphosphonate inhibits the expression of cyclin A2 at the transcriptional level in normal human oral keratinocytes. Diphosphonates 0-14 cyclin A2 Homo sapiens 42-51 28337806-2 2017 The antiresorptive potency of the nitrogen-containing bisphosphonates on bone in vivo is now recognized to depend upon two key properties, namely mineral binding affinity and inhibitory activity on farnesyl pyrophosphate synthase (FPPS), and these properties vary independently of each other in individual bisphosphonates. Diphosphonates 54-69 farnesyl diphosphate synthase Rattus norvegicus 198-229 28337806-2 2017 The antiresorptive potency of the nitrogen-containing bisphosphonates on bone in vivo is now recognized to depend upon two key properties, namely mineral binding affinity and inhibitory activity on farnesyl pyrophosphate synthase (FPPS), and these properties vary independently of each other in individual bisphosphonates. Diphosphonates 54-69 farnesyl diphosphate synthase Rattus norvegicus 231-235 28337806-4 2017 Among these is a highly potent bisphosphonate, 1-fluoro-2-(imidazo-[1,2 alpha]pyridin-3-yl)-ethyl-bisphosphonate, also known as OX14, which is a strong inhibitor of FPPS, but has lower binding affinity for bone mineral than most of the commonly studied bisphosphonates. Diphosphonates 31-45 farnesyl diphosphate synthase Rattus norvegicus 165-169 28337806-4 2017 Among these is a highly potent bisphosphonate, 1-fluoro-2-(imidazo-[1,2 alpha]pyridin-3-yl)-ethyl-bisphosphonate, also known as OX14, which is a strong inhibitor of FPPS, but has lower binding affinity for bone mineral than most of the commonly studied bisphosphonates. Diphosphonates 253-268 farnesyl diphosphate synthase Rattus norvegicus 165-169 28540505-7 2017 CTX also remained in the premenopausal range in 14 out of 17 patients who discontinued Dmab after multiple (4.1 +- 1.4, range 2-7) injections but were previously exposed to BPs (mean exposure 6.9 +- 5.8 years, range 11 months-15 years; mean time interval between BP exposure and Dmab initiation 25 +- 10 months, range 0-48). Diphosphonates 173-175 cytochrome P450 family 27 subfamily A member 1 Homo sapiens 0-3 28540505-9 2017 CONCLUSION: The higher CTX levels occurring after Dmab discontinuation in patients who have received multiple injections may be prevented by prior exposure to BPs. Diphosphonates 159-162 cytochrome P450 family 27 subfamily A member 1 Homo sapiens 23-26 28809381-0 2017 Serum levels of RANKL and OPG, and the RANKL/OPG ratio in bisphosphonate-related osteonecrosis of the jaw: Are they useful biomarkers for the advanced stages of osteonecrosis? Diphosphonates 58-72 TNF receptor superfamily member 11b Homo sapiens 45-48 28540505-1 2017 Discontinuation of denosumab (Dmab) therapy is associated with lower serum CTX levels in osteoporotic patients previously exposed to bisphosphonates compared to those who were not. Diphosphonates 133-148 cytochrome P450 family 27 subfamily A member 1 Homo sapiens 75-78 28540505-5 2017 CTX levels were analyzed according to the number of Dmab injections (1 or multiple) and previous exposure to BPs. Diphosphonates 109-112 cytochrome P450 family 27 subfamily A member 1 Homo sapiens 0-3 28540505-7 2017 CTX also remained in the premenopausal range in 14 out of 17 patients who discontinued Dmab after multiple (4.1 +- 1.4, range 2-7) injections but were previously exposed to BPs (mean exposure 6.9 +- 5.8 years, range 11 months-15 years; mean time interval between BP exposure and Dmab initiation 25 +- 10 months, range 0-48). Diphosphonates 173-176 cytochrome P450 family 27 subfamily A member 1 Homo sapiens 0-3 28936298-5 2017 RESULTS: The use of L-PRF for the treatment of MRONJ is really effective, especially when it is performed with a simultaneous application of L-PRF and morphogenetic protein-2 (BMP-2), even in patients submitted for long periods of time to therapy with intravenous bisphosphonates. Diphosphonates 264-279 bone morphogenetic protein 2 Homo sapiens 176-181 28731328-2 2017 Here, we report on the assessment of the effect of hydroxyapatite (HAp) nanoparticles loaded with medronate, the simplest bisphosphonate, as a bone-targeting agent and JQ1, a small-molecule bromodomain inhibitor, as a chemotherapeutic in different 2D and 3D K7M2 OS in vitro models. Diphosphonates 122-136 BAG cochaperone 1 Homo sapiens 67-70 28699744-4 2017 Studies with doubly radiolabeled 16 provide a proof-of-concept for the use of a cathepsin K cleavable peptide-linked conjugate for targeting of bisphosphonate prodrugs to bone and slow release liberation of the active constituents in vivo. Diphosphonates 144-158 cathepsin K Homo sapiens 80-91 28559264-3 2017 The target of the most potent bisphosphonates is the isoprenoid biosynthesis pathway enzyme farnesyl diphosphate synthase (FPPS). Diphosphonates 30-45 farnesyl diphosphate synthase Homo sapiens 123-127 28631130-0 2017 New insights into human farnesyl pyrophosphate synthase inhibition by second-generation bisphosphonate drugs. Diphosphonates 88-102 farnesyl diphosphate synthase Homo sapiens 24-55 26174121-3 2017 Localized delivery using biodegradable materials, such as polylactic acid (PLA) and hydroxyapatite (HAp), which are ideal in this approach, have been used in this study to investigate the dissolution of clodronate (non-nitrogen-containing bisphosphonate) in a new release system. Diphosphonates 239-253 retinoic acid receptor beta Homo sapiens 100-103 28404687-0 2017 Selective Calcium-Dependent Inhibition of ATP-Gated P2X3 Receptors by Bisphosphonate-Induced Endogenous ATP Analog ApppI. Diphosphonates 70-84 purinergic receptor P2X 3 Homo sapiens 52-56 28611279-5 2017 Given that MMP-2 is systemically expressed, we used novel "bone-seeking" bisphosphonate based MMP-2 specific inhibitors (BMMPIs) to target the skeletal tissue thereby circumventing potential off-target effects of MMP-2 inhibition outside the bone marrow-tumor microenvironment. Diphosphonates 73-87 matrix metallopeptidase 2 Homo sapiens 11-16 28611279-5 2017 Given that MMP-2 is systemically expressed, we used novel "bone-seeking" bisphosphonate based MMP-2 specific inhibitors (BMMPIs) to target the skeletal tissue thereby circumventing potential off-target effects of MMP-2 inhibition outside the bone marrow-tumor microenvironment. Diphosphonates 73-87 matrix metallopeptidase 2 Homo sapiens 94-99 28611279-5 2017 Given that MMP-2 is systemically expressed, we used novel "bone-seeking" bisphosphonate based MMP-2 specific inhibitors (BMMPIs) to target the skeletal tissue thereby circumventing potential off-target effects of MMP-2 inhibition outside the bone marrow-tumor microenvironment. Diphosphonates 73-87 matrix metallopeptidase 2 Homo sapiens 94-99 28416300-5 2017 Herein, we determined that the administration of PPi and the bisphosphonate etidronate to Abcc6-/- mice fully inhibited the acute dystrophic cardiac calcification phenotype, whereas alendronate had no significant effect. Diphosphonates 61-75 ATP-binding cassette, sub-family C (CFTR/MRP), member 6 Mus musculus 90-95 28387378-5 2017 In fact, we demonstrate that TNFalpha-, IL-1alpha/beta- or IL-6-deficient mice as well as wild-type mice administered a TNFalpha-inhibitor were significantly resistant to development of osteonecrosis accompanying infectious myelitis, even under bisphosphonate treatment. Diphosphonates 245-259 tumor necrosis factor Mus musculus 29-37 28275838-12 2017 Compared with usual care, CaB increased rates of bisphosphonate treatment by 4.3 to 17.5% (p < 0.001). Diphosphonates 49-63 neural proliferation, differentiation and control 1 Homo sapiens 26-29 28299378-1 2017 A first intravenous dose of bisphosphonates may be associated with an acute-phase response (APR). Diphosphonates 28-43 phorbol-12-myristate-13-acetate-induced protein 1 Homo sapiens 92-95 28299378-2 2017 In bisphosphonate-naive women with postmenopausal osteoporosis, the characteristics and frequency of APR may differ by compound. Diphosphonates 3-17 phorbol-12-myristate-13-acetate-induced protein 1 Homo sapiens 101-104 28299378-3 2017 Prior bisphosphonate exposure was predictive of APR risk and severity. Diphosphonates 6-20 phorbol-12-myristate-13-acetate-induced protein 1 Homo sapiens 48-51 28299378-4 2017 INTRODUCTION: Intravenous (IV) administration of bisphosphonates (BP), such as zoledronate (ZOL) and ibandronate (IBN), may be associated with an APR. Diphosphonates 49-64 phorbol-12-myristate-13-acetate-induced protein 1 Homo sapiens 146-149 28299378-4 2017 INTRODUCTION: Intravenous (IV) administration of bisphosphonates (BP), such as zoledronate (ZOL) and ibandronate (IBN), may be associated with an APR. Diphosphonates 66-68 phorbol-12-myristate-13-acetate-induced protein 1 Homo sapiens 146-149 28299378-6 2017 The aim of the present study was to evaluate the characteristics of APR (rates, signs and symptoms, severity), in the absence of any preventive measure, after a first IV application of ZOL or IBN in patients naive or previously exposed to BP in a real-world clinical setting. Diphosphonates 239-241 phorbol-12-myristate-13-acetate-induced protein 1 Homo sapiens 68-71 28299378-11 2017 Corresponding APR rates in the subgroup of BP-naive patients were 55.6 and 32.4%, respectively (p < 0.001). Diphosphonates 43-45 phorbol-12-myristate-13-acetate-induced protein 1 Homo sapiens 14-17 28299378-13 2017 Prior BP exposure was predictive of both APR risk and severity, and lower serum 25-hydroxy vitamin D (25(OH)D) levels were possibly predictive of severity. Diphosphonates 6-8 phorbol-12-myristate-13-acetate-induced protein 1 Homo sapiens 41-44 28299378-14 2017 CONCLUSIONS: In a real-world setting, APR rates with ZOL and IBN may be higher than reported in randomised controlled trials and may differ by compound, prior BP exposure, and serum 25(OH)D levels. Diphosphonates 159-161 phorbol-12-myristate-13-acetate-induced protein 1 Homo sapiens 38-41 28220293-9 2017 The expression of NFkappaB1 and 2, OPG, Spp1 and Runx2 in the ossification zone was reduced by both bisphosphonates. Diphosphonates 100-115 TNF receptor superfamily member 11B Rattus norvegicus 35-38 28220293-9 2017 The expression of NFkappaB1 and 2, OPG, Spp1 and Runx2 in the ossification zone was reduced by both bisphosphonates. Diphosphonates 100-115 secreted phosphoprotein 1 Rattus norvegicus 40-44 28220293-9 2017 The expression of NFkappaB1 and 2, OPG, Spp1 and Runx2 in the ossification zone was reduced by both bisphosphonates. Diphosphonates 100-115 RUNX family transcription factor 2 Rattus norvegicus 49-54 28177277-0 2017 Prevalence of bisphosphonate therapy in women with breast cancer treated with aromatase inhibitors in Germany : . Diphosphonates 14-28 cytochrome P450 family 19 subfamily A member 1 Homo sapiens 78-87 28177277-1 2017 PURPOSE: The aim of this study is to analyze the prevalence of bisphosphonate therapy in women with breast cancer (BC) treated with aromatase inhibitors (AI) in Germany. Diphosphonates 63-77 cytochrome P450 family 19 subfamily A member 1 Homo sapiens 132-141 28387378-5 2017 In fact, we demonstrate that TNFalpha-, IL-1alpha/beta- or IL-6-deficient mice as well as wild-type mice administered a TNFalpha-inhibitor were significantly resistant to development of osteonecrosis accompanying infectious myelitis, even under bisphosphonate treatment. Diphosphonates 245-259 interleukin 1 alpha Mus musculus 40-49 28387378-5 2017 In fact, we demonstrate that TNFalpha-, IL-1alpha/beta- or IL-6-deficient mice as well as wild-type mice administered a TNFalpha-inhibitor were significantly resistant to development of osteonecrosis accompanying infectious myelitis, even under bisphosphonate treatment. Diphosphonates 245-259 interleukin 6 Mus musculus 59-63 28387378-5 2017 In fact, we demonstrate that TNFalpha-, IL-1alpha/beta- or IL-6-deficient mice as well as wild-type mice administered a TNFalpha-inhibitor were significantly resistant to development of osteonecrosis accompanying infectious myelitis, even under bisphosphonate treatment. Diphosphonates 245-259 tumor necrosis factor Mus musculus 120-128 27683176-8 2017 A similar advantageous effect, but statistically underpowered, was found in estrogen receptor (ER)-positive, ER-negative, and HER2neu-positive tumors.Conclusions: The use of oral bisphosphonates, by postmenopausal, probably osteoporotic, women initiated after diagnosis of breast cancer was associated with a significant improvement in overall and breast-specific odds of survival. Diphosphonates 179-194 estrogen receptor 1 Homo sapiens 76-93 27683176-8 2017 A similar advantageous effect, but statistically underpowered, was found in estrogen receptor (ER)-positive, ER-negative, and HER2neu-positive tumors.Conclusions: The use of oral bisphosphonates, by postmenopausal, probably osteoporotic, women initiated after diagnosis of breast cancer was associated with a significant improvement in overall and breast-specific odds of survival. Diphosphonates 179-194 estrogen receptor 1 Homo sapiens 95-97 27683176-8 2017 A similar advantageous effect, but statistically underpowered, was found in estrogen receptor (ER)-positive, ER-negative, and HER2neu-positive tumors.Conclusions: The use of oral bisphosphonates, by postmenopausal, probably osteoporotic, women initiated after diagnosis of breast cancer was associated with a significant improvement in overall and breast-specific odds of survival. Diphosphonates 179-194 estrogen receptor 1 Homo sapiens 109-111 27683176-8 2017 A similar advantageous effect, but statistically underpowered, was found in estrogen receptor (ER)-positive, ER-negative, and HER2neu-positive tumors.Conclusions: The use of oral bisphosphonates, by postmenopausal, probably osteoporotic, women initiated after diagnosis of breast cancer was associated with a significant improvement in overall and breast-specific odds of survival. Diphosphonates 179-194 erb-b2 receptor tyrosine kinase 2 Homo sapiens 126-133 28257626-10 2017 CONCLUSION: This case expands the mutation spectrum of BMP1, strengthens the correlation between genotype and phenotype, and supports the benefits of bisphosphonate in OI patients with BMP1 mutations. Diphosphonates 150-164 bone morphogenetic protein 1 Homo sapiens 185-189 28243105-0 2017 Short-term bisphosphonate treatment reduces serum 25(OH) vitamin D3 and alters values of parathyroid hormone, pentosidine, and bone metabolic markers. Diphosphonates 11-25 parathyroid hormone Homo sapiens 89-108 27939801-12 2017 A Medline search identified 6 cases of bisphosphonate-related CPDD, including 2 due to pamidronate, 2 to etidronate, 1 to alendronic acid, and 1 to neridronic acid. Diphosphonates 39-53 CCAL1 Homo sapiens 62-66 27939801-14 2017 Bisphosphonate-induced CPDD is a rare eventuality that should nevertheless be borne in mind by rheumatologists. Diphosphonates 0-14 CCAL1 Homo sapiens 23-27 27939801-15 2017 Also, in patients with CPDD while taking bisphosphonate therapy, a role for the drug in the symptoms should be considered. Diphosphonates 41-55 CCAL1 Homo sapiens 23-27 28211502-0 2017 Bisphosphonates enhance antitumor effect of EGFR-TKIs in patients with advanced EGFR mutant NSCLC and bone metastases. Diphosphonates 0-15 epidermal growth factor receptor Homo sapiens 44-48 28211502-0 2017 Bisphosphonates enhance antitumor effect of EGFR-TKIs in patients with advanced EGFR mutant NSCLC and bone metastases. Diphosphonates 0-15 epidermal growth factor receptor Homo sapiens 80-84 28211502-1 2017 Whether bisphosphonates could enhance the effect of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) in non-small-cell lung cancer (NSCLC) patients with EGFR mutation and bone metastases (BM) remains unknown. Diphosphonates 8-23 epidermal growth factor receptor Homo sapiens 52-84 28211502-1 2017 Whether bisphosphonates could enhance the effect of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) in non-small-cell lung cancer (NSCLC) patients with EGFR mutation and bone metastases (BM) remains unknown. Diphosphonates 8-23 epidermal growth factor receptor Homo sapiens 86-90 28211502-1 2017 Whether bisphosphonates could enhance the effect of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) in non-small-cell lung cancer (NSCLC) patients with EGFR mutation and bone metastases (BM) remains unknown. Diphosphonates 8-23 epidermal growth factor receptor Homo sapiens 178-182 28211502-5 2017 Comparing to TKIs alone, EGFR-TKIs plus bisphosphonates had a statistically significant longer progression-free survival (PFS: 11.6 vs. 9.3 months; HR = 0.68, P = 0.009), while a similar overall survival (OS: 20.5 vs. 19.5 months; HR = 0.95, P = 0.743) in patients with EGFR-mutant NSCLC and BM. Diphosphonates 40-55 epidermal growth factor receptor Homo sapiens 270-274 28211502-8 2017 In conclusion, EGFR mutation was the significant independent prognostic factor for OS and the addition of bisphosphonates to EGFR-TKIs could enhance the antitumor effect of EGFR-TKIs in patients with EGFR-mutant NSCLC and BM. Diphosphonates 106-121 epidermal growth factor receptor Homo sapiens 125-129 28211502-8 2017 In conclusion, EGFR mutation was the significant independent prognostic factor for OS and the addition of bisphosphonates to EGFR-TKIs could enhance the antitumor effect of EGFR-TKIs in patients with EGFR-mutant NSCLC and BM. Diphosphonates 106-121 epidermal growth factor receptor Homo sapiens 125-129 28211502-8 2017 In conclusion, EGFR mutation was the significant independent prognostic factor for OS and the addition of bisphosphonates to EGFR-TKIs could enhance the antitumor effect of EGFR-TKIs in patients with EGFR-mutant NSCLC and BM. Diphosphonates 106-121 epidermal growth factor receptor Homo sapiens 125-129 27876532-1 2017 This systematic review evaluated the efficacy of the morning fasting serum C-terminal telopeptide (CTX) test in predicting the development of bisphosphonate-related osteonecrosis of the jaw (BRONJ). Diphosphonates 142-156 cytochrome P450 family 27 subfamily A member 1 Homo sapiens 99-102 27817114-0 2017 Nitrogen-containing bisphosphonate induces a newly discovered hematopoietic structure in the omentum of an anemic mouse model by stimulating G-CSF production. Diphosphonates 20-34 peripheral blood stem cell response to granulocyte colony stimulating factor 1 Mus musculus 141-146 28561722-1 2017 Clinical trials and meta-analyses investigating bisphosphonates as an adjuvant breast cancer therapy have shown a consistent trend, with postmenopausal women and women receiving ovarian suppression with gonadotropin-releasing hormone therapy gaining improved breast cancer outcomes with the use of adjuvant bisphosphonate therapy. Diphosphonates 48-62 gonadotropin releasing hormone 1 Homo sapiens 203-233 27567012-0 2017 IL-36 Induces Bisphosphonate-Related Osteonecrosis of the Jaw-Like Lesions in Mice by Inhibiting TGF-beta-Mediated Collagen Expression. Diphosphonates 14-28 transforming growth factor, beta 1 Mus musculus 97-105 27789416-4 2017 Patient 1: NBAS c.5741G>A p.(Arg1914His); c.3010C>T p.(Arg1004*) in a 10-year old boy with significant short stature, bone fragility requiring treatment with bisphosphonates, developmental delay and immunodeficiency. Diphosphonates 164-179 NBAS subunit of NRZ tethering complex Homo sapiens 11-15 28367895-0 2017 Effect of bisphosphonate as an adjunct treatment for chronic periodontitis on gingival crevicuar fluid levels of nuclear factor-kappaB ligand (RANKL) and osteoprotegerin in postmenopausal osteoporosis. Diphosphonates 10-24 TNF superfamily member 11 Homo sapiens 143-148 26762133-6 2017 In addition, the patients in the switch-to-DMAb group showed a significant decrease compared to those in the switch-to-BP group in TRACP-5b (-55.8 vs. -32.8 %; P < 0.01) and ucOC (-85.5 vs. -65.0 %; P < 0.001), while no significant difference was observed in PINP (-67.5 vs. -62.1 %). Diphosphonates 119-121 acid phosphatase 5, tartrate resistant Homo sapiens 131-139 28367895-0 2017 Effect of bisphosphonate as an adjunct treatment for chronic periodontitis on gingival crevicuar fluid levels of nuclear factor-kappaB ligand (RANKL) and osteoprotegerin in postmenopausal osteoporosis. Diphosphonates 10-24 TNF receptor superfamily member 11b Homo sapiens 154-169 27562566-5 2017 We previously identified high serum CKbb levels in 18 children with osteogenesis imperfect (OI) type 1 treated for 1 year with bisphosphonate (neridronate). Diphosphonates 127-141 creatine kinase B Homo sapiens 36-40 27562566-12 2017 This approach could be employed for verifying the usefulness of serum CKbb as a biochemical marker in patients receiving prolonged bisphosphonate treatment. Diphosphonates 131-145 creatine kinase B Homo sapiens 70-74 27888633-5 2016 Based on the similarities in inflammatory responses to bisphosphonates and Toll-like receptor (TLR) agonists, we hypothesized that TLR9 expression may affect bisphosphonate responses in cells. Diphosphonates 55-69 toll like receptor 9 Homo sapiens 131-135 27888633-0 2016 Toll-like receptor 9 expression is associated with breast cancer sensitivity to the growth inhibitory effects of bisphosphonates in vitro and in vivo. Diphosphonates 113-128 toll like receptor 9 Homo sapiens 0-20 27888633-6 2016 We compared bisphosphonate effects in breast cancer cell lines with low or high TLR9 expression. Diphosphonates 12-26 toll like receptor 9 Homo sapiens 80-84 27888633-5 2016 Based on the similarities in inflammatory responses to bisphosphonates and Toll-like receptor (TLR) agonists, we hypothesized that TLR9 expression may affect bisphosphonate responses in cells. Diphosphonates 55-70 toll like receptor 9 Homo sapiens 131-135 27888633-7 2016 We discovered that cells with decreased TLR9 expression are significantly more sensitive to the growth-inhibitory effects of bisphosphonates in vitro and in vivo. Diphosphonates 125-140 toll like receptor 9 Homo sapiens 40-44 27888633-10 2016 However, TLR9 shRNA cells exhibited increased sensitivity to ApppI, a metabolite that accumulates in cells after bisphosphonate treatment. Diphosphonates 113-127 toll like receptor 9 Homo sapiens 9-13 27888633-11 2016 We conclude that decreased TLR9-expression sensitizes breast cancer cells to the growth inhibitory effects of bisphosphonates. Diphosphonates 110-125 toll like receptor 9 Homo sapiens 27-31 27888633-12 2016 Our results suggest that TLR9 should be studied as a potential biomarker for adjuvant bisphosphonate sensitivity among breast cancer patients. Diphosphonates 86-100 toll like receptor 9 Homo sapiens 25-29 27926689-0 2016 Bisphosphonates Are Not Always Helpful: Commentary on an article by Hae-Seong Lim, MD, et al. Diphosphonates 0-15 PDZ and LIM domain 5 Homo sapiens 78-81 27482608-13 2016 ABBREVIATIONS: ALP = alkaline phosphatase beta-CTX = cross-linked C-telopeptide of type I collagen BMD = bone mineral density BP = bisphosphonate DXA = dual-energy X-ray absorptiometry 25OHD = 25-hydroxyvitamin D OI = osteogenesis imperfecta PTH = parathyroid hormone. Diphosphonates 131-145 alkaline phosphatase, placental Homo sapiens 15-18 27934558-5 2016 Drugs such as phosphate binders, bisphosphonate, and estrogens have various effects on circulating fibroblast growth factor 23 levels. Diphosphonates 33-47 fibroblast growth factor 23 Homo sapiens 99-126 27670281-10 2016 Moreover, the levels of P1NP (p=0.016) and TRACP-5b (p=0.015) were found to be significantly lower in patients with AFFs than in patients with TFFs in a subgroup analysis of BPs users. Diphosphonates 174-177 acid phosphatase 5, tartrate resistant Homo sapiens 43-51 27746180-6 2016 Thus, inhibition of bone resorption by bisphosphonate, such as ZOL, would be one of the advantageous ways to augment the new bone formation induced by rh-BMP-2, and moreover local co-application of ZOL using beta-TCP as a carrier can be a useful material for long term suppression of osteoclastic resorption and thereby maintain the structure of new bone formation induced by rh-BMP-2. Diphosphonates 39-53 bone morphogenetic protein 2 Homo sapiens 154-159 27746180-6 2016 Thus, inhibition of bone resorption by bisphosphonate, such as ZOL, would be one of the advantageous ways to augment the new bone formation induced by rh-BMP-2, and moreover local co-application of ZOL using beta-TCP as a carrier can be a useful material for long term suppression of osteoclastic resorption and thereby maintain the structure of new bone formation induced by rh-BMP-2. Diphosphonates 39-53 bone morphogenetic protein 2 Homo sapiens 379-384 26689567-2 2016 It was already proved that some clinically relevant BPs can inhibit a class of enzymes called matrix metalloproteinases (MMPs), required during tissue remodelling. Diphosphonates 52-55 matrix metallopeptidase 8 Homo sapiens 121-125 27387541-0 2016 Modulation of paraoxonase 1 (PON1) activity and protein N-homocysteinylation by bisphosphonates in rats. Diphosphonates 80-95 paraoxonase 1 Rattus norvegicus 14-27 27387541-2 2016 As osteoporosis and atherosclerosis share some common risk factors and frequently coexist in the same patients, we examined the effect of bisphosphonates on paraoxonase 1 (PON1) - the high density lipoprotein-associated enzyme with potent anti-atherosclerotic activity. Diphosphonates 138-153 paraoxonase 1 Homo sapiens 157-170 27387541-2 2016 As osteoporosis and atherosclerosis share some common risk factors and frequently coexist in the same patients, we examined the effect of bisphosphonates on paraoxonase 1 (PON1) - the high density lipoprotein-associated enzyme with potent anti-atherosclerotic activity. Diphosphonates 138-153 paraoxonase 1 Homo sapiens 172-176 27387541-9 2016 CONCLUSIONS: Bisphosphonates have differential effects on PON1 activity. Diphosphonates 13-28 paraoxonase 1 Rattus norvegicus 58-62 27535783-0 2016 The effect of bisphosphonate treatment on osteoclast precursor cells in postmenopausal osteoporosis: The TRIO study. Diphosphonates 14-28 trio Rho guanine nucleotide exchange factor Homo sapiens 105-109 27638613-5 2016 Because some bisphosphonates have been identified as selective galactosyltransferase inhibitors, we verify the binding affinity to a generated model of the enzyme UGT8 and investigate the molecular mechanisms of UGT8-ligand interactions of the bisphosphonate zoledronate by a multistep framework combining homology modeling, molecular docking, and molecular dynamics simulations. Diphosphonates 13-28 UDP glycosyltransferase 8 Homo sapiens 163-167 27638613-5 2016 Because some bisphosphonates have been identified as selective galactosyltransferase inhibitors, we verify the binding affinity to a generated model of the enzyme UGT8 and investigate the molecular mechanisms of UGT8-ligand interactions of the bisphosphonate zoledronate by a multistep framework combining homology modeling, molecular docking, and molecular dynamics simulations. Diphosphonates 13-27 UDP glycosyltransferase 8 Homo sapiens 163-167 27611499-2 2016 By using a viologen-functionalized diphosphonate linker, two terbium phosphonate compounds (Tb-1 and Tb-2) have been constructed, which display reversible photochromic reactions in response to UV light and soft X-ray irradiation. Diphosphonates 35-48 receptor accessory protein 5 Homo sapiens 92-105 27376840-2 2016 Although bisphosphonates are safety drugs, they have numerous side-effects such as arthralgia, elevated erythrocyte sedimentation rate and C-reactive protein, gastrointestinal disturbances, and flu-like illness with symptoms of fatigue, fever, chills, malaise, and myalgia. Diphosphonates 9-24 C-reactive protein Homo sapiens 139-157 27041582-4 2016 The treatment of bisphosphonate drugs, either alendronate (ALN) or zoledronic acid (ZOL), opened Cx43 hemichannels in osteocytes. Diphosphonates 17-31 gap junction protein, alpha 3 Mus musculus 97-101 27041582-5 2016 Conditioned media (CM) collected from MLO-Y4 osteocyte cells treated with bisphosphonates inhibited the anchorage-independent growth, migration and invasion of MDA-MB-231 human breast cancer cells and Py8119 mouse mammary carcinoma cells, and this inhibitory effect was attenuated with Cx43(E2), a specific hemichannel-blocking antibody. Diphosphonates 74-89 gap junction protein, alpha 3 Mus musculus 286-290 27450065-6 2016 We also observed the effects of bisphosphonates in OI patients with WNT1 mutations. Diphosphonates 32-47 Wnt family member 1 Homo sapiens 68-72 27477003-0 2016 Atypical femur fracture in an adolescent boy treated with bisphosphonates for X-linked osteoporosis based on PLS3 mutation. Diphosphonates 58-73 plastin 3 Homo sapiens 109-113 27477003-2 2016 We report a case of an 18-year-old patient with juvenile osteoporosis based on X-linked osteoporosis due to a PLS3 mutation who developed a low trauma femoral fracture after seven years of intravenous and two years of oral bisphosphonate use, fulfilling the revised ASBMR diagnostic criteria of an AFF. Diphosphonates 223-237 plastin 3 Homo sapiens 110-114 26624882-0 2016 Bisphosphonates enhance EGFR-TKIs efficacy in advanced NSCLC patients with EGFR activating mutation: A retrospective study. Diphosphonates 0-15 epidermal growth factor receptor Homo sapiens 24-28 26624882-0 2016 Bisphosphonates enhance EGFR-TKIs efficacy in advanced NSCLC patients with EGFR activating mutation: A retrospective study. Diphosphonates 0-15 epidermal growth factor receptor Homo sapiens 75-79 26624882-2 2016 We aimed to evaluate whether the combination of bisphosphonates with tyrosine kinase inhibitors of EGFR (EGFR-TKIs) could obtain a synergistic effect on advanced NSCLC patients with EGFR mutations. Diphosphonates 48-63 epidermal growth factor receptor Homo sapiens 105-114 26624882-2 2016 We aimed to evaluate whether the combination of bisphosphonates with tyrosine kinase inhibitors of EGFR (EGFR-TKIs) could obtain a synergistic effect on advanced NSCLC patients with EGFR mutations. Diphosphonates 48-63 epidermal growth factor receptor Homo sapiens 105-109 26624882-10 2016 CONCLUSIONS: Concomitant use of bisphosphonates and EGFR-TKIs improves therapeutic efficacy and brings survival benefits to NSCLC patients with EGFR mutation and bone metastases. Diphosphonates 32-47 epidermal growth factor receptor Homo sapiens 144-148 27571880-2 2016 The most active compounds were found to be bisphosphonates with electron-withdrawing aryl-alkyl side chains which inhibited the growth of Gram-negative bacteria (Acinetobacter baumannii, Klebsiella pneumoniae, Escherichia coli, and Pseudomonas aeruginosa) at ~1-4 mug mL-1 levels. Diphosphonates 43-58 L1 cell adhesion molecule Mus musculus 268-272 27460418-4 2016 We synthesised non-hydrolysable bisphosphonate analogues and crystallised the analogues in complex with mammalian PPIP5K2 kinase. Diphosphonates 32-46 diphosphoinositol pentakisphosphate kinase 2 Homo sapiens 114-121 27757355-0 2016 Bilateral Maxillary Reconstruction Using Fibular Flap in Bisphosphonate-related Osteonecrosis. Diphosphonates 57-71 arachidonate 5-lipoxygenase activating protein Homo sapiens 49-53 27757355-1 2016 Recent reports have shown successful transfer of vascularized fibular flap in bisphosphonate-induced mandibular osteonecrosis. Diphosphonates 78-92 arachidonate 5-lipoxygenase activating protein Homo sapiens 70-74 27757355-2 2016 We present a case of a 50-year-old patient who presented with bisphosphonate-related osteonecrosis of bilateral maxilla, which is reconstructed using a fibular flap. Diphosphonates 62-76 arachidonate 5-lipoxygenase activating protein Homo sapiens 160-164 27326918-6 2016 The mRNA expression levels of receptor activator of nuclear factor kappa-B ligand and osteoprotegerin were significantly decreased in BP-treated MSCs. Diphosphonates 134-136 TNF superfamily member 11 Rattus norvegicus 30-81 27326918-6 2016 The mRNA expression levels of receptor activator of nuclear factor kappa-B ligand and osteoprotegerin were significantly decreased in BP-treated MSCs. Diphosphonates 134-136 TNF receptor superfamily member 11B Rattus norvegicus 86-101 28228794-1 2016 BACKGROUND: We report on the clinical and biochemical outcomes in a 20-year-old male suffering from active craniofacial monostotic fibrous dysplasia (MFD) of the left mandible treated with the RANK-L inhibitor, denosumab, following unsatisfactory responses to prior long-term bisphosphonates therapy. Diphosphonates 276-291 TNF superfamily member 11 Homo sapiens 193-199 27491573-0 2016 Spontaneous Osteonecrosis of the Jaw During Bisphosphonate Therapy: An Unusual Etiology of the Numb Chin Syndrome. Diphosphonates 44-58 NUMB endocytic adaptor protein Homo sapiens 95-99 27491573-3 2016 The authors present the case of a patient with long-standing multiple myeloma, suffering from numb chin syndrome caused by a spontaneous osteonecrosis of the jaw after bisphosphonate therapy. Diphosphonates 168-182 NUMB endocytic adaptor protein Homo sapiens 94-98 27428767-5 2016 This fluorescence probe was used to reveal the inhibitory mechanism of zoledronate, a bisphosphonate drug that targets human FPPS and possibly GGPPS. Diphosphonates 86-100 farnesyl diphosphate synthase Homo sapiens 125-129 27428767-5 2016 This fluorescence probe was used to reveal the inhibitory mechanism of zoledronate, a bisphosphonate drug that targets human FPPS and possibly GGPPS. Diphosphonates 86-100 geranylgeranyl diphosphate synthase 1 Homo sapiens 143-148 27301549-6 2016 Several studies have evaluated the efficacy of bisphosphonates and their lasting effects as treatment for osteoporosis using bone turnover measured by NaF-PET. Diphosphonates 47-62 C-X-C motif chemokine ligand 8 Homo sapiens 151-154 27491286-10 2016 In the BP group, there was a 13.31 % reduced muscle cross-sectional area around the proximal thigh (p = 0.013); cortical CSA was smaller by 5.3 % (p = 0.043); however, total and medullary CSA, as well as cortical vBMD and the polar bone stress-strain index of the femoral shaft were similar in the two groups. Diphosphonates 7-9 ERCC excision repair 8, CSA ubiquitin ligase complex subunit Homo sapiens 188-191 27491286-13 2016 CONCLUSION: Differences in cortical CSA between BP-treated and BP-naive postmenopausal RA patients were found to be associated only with differences in age, time since menopause and muscle cross-sectional area around the proximal thigh. Diphosphonates 48-50 ERCC excision repair 8, CSA ubiquitin ligase complex subunit Homo sapiens 36-39 27491286-13 2016 CONCLUSION: Differences in cortical CSA between BP-treated and BP-naive postmenopausal RA patients were found to be associated only with differences in age, time since menopause and muscle cross-sectional area around the proximal thigh. Diphosphonates 63-65 ERCC excision repair 8, CSA ubiquitin ligase complex subunit Homo sapiens 36-39 27525578-6 2016 Cathepsin K-inhibiting antibody could be an alternative if approved; although an antiresorptive, it maintains bone formation, in contrast with bisphosphonates, and can be probably used for long-term treatment. Diphosphonates 143-158 cathepsin K Homo sapiens 0-11 27218688-1 2016 A bis(phosphonate) conjugate of 2"-O-methyl oligoribonucleotide (microRNA-21) was synthesized and used as a bone-targeting carrier in the systemic delivery of a (68)Ga-1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA)-chelated 2"-O-methyl oligoribonucleotide (anti-microRNA-21). Diphosphonates 2-18 microRNA 21 Rattus norvegicus 65-76 27218688-1 2016 A bis(phosphonate) conjugate of 2"-O-methyl oligoribonucleotide (microRNA-21) was synthesized and used as a bone-targeting carrier in the systemic delivery of a (68)Ga-1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA)-chelated 2"-O-methyl oligoribonucleotide (anti-microRNA-21). Diphosphonates 2-18 microRNA 21 Rattus norvegicus 267-278 25894100-7 2016 All BPs, except etidronate, were cytotoxic, as indicated by increased caspase-3/7 activity and numbers of Annexin-fluorescein isothiocyanate positive cells in ESCC cell lines. Diphosphonates 4-7 caspase 3 Homo sapiens 70-79 25894100-9 2016 In addition, Cyclin D1 protein expression levels were decreased by second- and third-generation BP treatment. Diphosphonates 96-98 cyclin D1 Homo sapiens 13-22 26984570-9 2016 Insufficient response to bisphosphonate therapy occurred more frequently in T3 than T1-2 (odds ratio = 4.43; 95 % CI = 1.02-21.25). Diphosphonates 25-39 CD6 molecule Homo sapiens 84-88 27049615-8 2016 Serum OC, urine PD and DPD index, as expressed as measured value/upper limit of normal value for age, decreased during the first 3 years of bisphosphonate therapy. Diphosphonates 140-154 bone gamma-carboxyglutamate protein Homo sapiens 6-8 26856585-14 2016 CONCLUSIONS: Our study demonstrated the key role of DKK1, RANKL, and TNF-alpha in regulating bone cell activity of subjects with OI untreated and treated with bisphosphonates. Diphosphonates 159-174 dickkopf WNT signaling pathway inhibitor 1 Homo sapiens 52-56 26856585-14 2016 CONCLUSIONS: Our study demonstrated the key role of DKK1, RANKL, and TNF-alpha in regulating bone cell activity of subjects with OI untreated and treated with bisphosphonates. Diphosphonates 159-174 TNF superfamily member 11 Homo sapiens 58-63 26856585-14 2016 CONCLUSIONS: Our study demonstrated the key role of DKK1, RANKL, and TNF-alpha in regulating bone cell activity of subjects with OI untreated and treated with bisphosphonates. Diphosphonates 159-174 tumor necrosis factor Homo sapiens 69-78 27147578-3 2016 LOX overexpression was positively correlated with resistance to radiation, doxorubin and mitoxantrone, but negatively correlated with resistance to bisphosphonate, PARP1 inhibitors, cisplatin, trabectedin and gemcitabine. Diphosphonates 148-162 lysyl oxidase Homo sapiens 0-3 26103458-0 2016 Simultaneous Application of Bone Morphogenetic Protein-2 and Platelet-Rich Fibrin for the Treatment of Bisphosphonate-Related Osteonecrosis of Jaw. Diphosphonates 103-117 bone morphogenetic protein 2 Homo sapiens 28-56 26927310-1 2016 Bisphosphonates are widely used to treat children with osteogenesis imperfecta (OI), a bone fragility disorder that is most often caused by mutations in COL1A1 or COL1A2. Diphosphonates 0-15 collagen type I alpha 1 chain Homo sapiens 153-159 26927310-1 2016 Bisphosphonates are widely used to treat children with osteogenesis imperfecta (OI), a bone fragility disorder that is most often caused by mutations in COL1A1 or COL1A2. Diphosphonates 0-15 collagen type I alpha 2 chain Homo sapiens 163-169 27112626-10 2016 We observed decrease in PYD and Dpd/creat in both groups; however, OC decreased only under bisph therapy. Diphosphonates 91-96 bone gamma-carboxyglutamate protein Homo sapiens 67-69 26995755-8 2016 Interestingly, bisphosphonates treatment significantly extended PFS and OS in patients with higher level of miR-214 comparing to patients without bisphosphonates treatment. Diphosphonates 15-30 microRNA 214 Homo sapiens 108-115 26954700-6 2016 Incubation of RALA with alendronate, etidronate, risedronate, or zoledronate provoked spontaneous electrostatic formation of cationic nanoparticles that did not exceed 100 nm in diameter and that were stable over a range of temperatures and for up to 6 h. The nanoparticles demonstrated a pH responsiveness, possibly indicative of a conformational change, that could facilitate release of the BP cargo in the endosomal environment. Diphosphonates 393-395 RAS like proto-oncogene A Homo sapiens 14-18 26954700-0 2016 Potentiating the Anticancer Properties of Bisphosphonates by Nanocomplexation with the Cationic Amphipathic Peptide, RALA. Diphosphonates 42-57 RAS like proto-oncogene A Homo sapiens 117-121 26340235-2 2016 In addition, bisphosphonate and the antagonist of transient receptor potential vanilloid type 1 (TRPV1), an acid-sensing nociceptor, improved the threshold value of pain-like behaviors accompanying an improvement in the acidic environment in the bone tissue based on osteoclast inactivation. Diphosphonates 13-27 transient receptor potential cation channel, subfamily V, member 1 Mus musculus 97-102 26874195-2 2016 Cancer-induced bone loss is usually treated with bisphosphonates or denosumab, an antibody against receptor activator of nuclear factor (NF)-kappaB ligand (RANKL). Diphosphonates 49-64 tumor necrosis factor (ligand) superfamily, member 11 Mus musculus 156-161 26777690-0 2016 Ligand Activation of ERRalpha by Cholesterol Mediates Statin and Bisphosphonate Effects. Diphosphonates 65-79 estrogen related receptor alpha Homo sapiens 21-29 26777690-6 2016 In bone, the effects of cholesterol, statin, and bisphosphonate on osteoclastogenesis require ERRalpha; and consequently, cholesterol-induced bone loss or bisphosphonate osteoprotection is lost in ERRalpha knockout mice. Diphosphonates 49-63 estrogen related receptor, alpha Mus musculus 94-102 26777690-6 2016 In bone, the effects of cholesterol, statin, and bisphosphonate on osteoclastogenesis require ERRalpha; and consequently, cholesterol-induced bone loss or bisphosphonate osteoprotection is lost in ERRalpha knockout mice. Diphosphonates 49-63 estrogen related receptor, alpha Mus musculus 197-205 26777690-8 2016 These findings reveal a key step in ERRalpha regulation and explain the actions of two highly prescribed drugs, statins and bisphosphonates. Diphosphonates 124-139 estrogen related receptor alpha Homo sapiens 36-44 26725718-4 2016 STUDY DESIGN: Activated THP-1 cells were exposed to .5 to 50 muM of nitrogen-containing bisphosphonates and .5 to 500 muM of clodronate. Diphosphonates 88-103 latexin Homo sapiens 61-64 25039439-9 2016 GMPs (45%) referred patients for dental assessments prior to commencing BPs with 71.9% of GDPs received such referrals. Diphosphonates 72-75 guanine monophosphate synthase Homo sapiens 0-4 26787490-7 2016 The stimulatory effects of HABP on the cohesion and toughness of the cements is hypothesized to derive from the strong affinity between the polymer-grafted bisphosphonate ligands and the calcium ions in the cement matrix. Diphosphonates 156-170 hyaluronan binding protein 2 Homo sapiens 27-31 26827062-5 2016 MATERIAL AND METHODS: This review of literature investigates four basic parameters in patients treated with bisphosphonates - parathyroid hormone (PTH), bisphosphonates, vitamin D, calcium, and jaw osteonecrosis - which are fundamental for assessing bone metabolism and so the efficacy and correct use of the drug. Diphosphonates 108-125 parathyroid hormone Homo sapiens 126-145 26827062-5 2016 MATERIAL AND METHODS: This review of literature investigates four basic parameters in patients treated with bisphosphonates - parathyroid hormone (PTH), bisphosphonates, vitamin D, calcium, and jaw osteonecrosis - which are fundamental for assessing bone metabolism and so the efficacy and correct use of the drug. Diphosphonates 108-123 parathyroid hormone Homo sapiens 126-145 26725718-7 2016 RESULTS: All bisphosphonates inhibited THP-1 cell adherence and survival dose and time dependently, significant for zoledronate, alendronate, pamidronate, and clodronate in high concentrations (50 muM and 500 muM; P < .05). Diphosphonates 13-28 latexin Homo sapiens 209-212 26725718-7 2016 RESULTS: All bisphosphonates inhibited THP-1 cell adherence and survival dose and time dependently, significant for zoledronate, alendronate, pamidronate, and clodronate in high concentrations (50 muM and 500 muM; P < .05). Diphosphonates 13-28 latexin Homo sapiens 197-200 26811636-4 2016 Recent data showing that some BPs inhibit human epidermal growth factor receptor (HER) signaling highlight a potential therapeutic opportunity in digestive cancers, many of which have alterations in the HER axis. Diphosphonates 30-33 epidermal growth factor receptor Homo sapiens 48-80 26610690-1 2016 An in situ cross-linkable hyaluronan hydrogel functionalized with bisphosphonate (BP) groups allows tunable release of bone morphogenetic protein-2 (BMP-2) determined by the amount of BP groups. Diphosphonates 66-80 bone morphogenetic protein 2 Homo sapiens 119-147 26610690-1 2016 An in situ cross-linkable hyaluronan hydrogel functionalized with bisphosphonate (BP) groups allows tunable release of bone morphogenetic protein-2 (BMP-2) determined by the amount of BP groups. Diphosphonates 66-80 bone morphogenetic protein 2 Homo sapiens 149-154 26610690-1 2016 An in situ cross-linkable hyaluronan hydrogel functionalized with bisphosphonate (BP) groups allows tunable release of bone morphogenetic protein-2 (BMP-2) determined by the amount of BP groups. Diphosphonates 82-84 bone morphogenetic protein 2 Homo sapiens 119-147 26610690-1 2016 An in situ cross-linkable hyaluronan hydrogel functionalized with bisphosphonate (BP) groups allows tunable release of bone morphogenetic protein-2 (BMP-2) determined by the amount of BP groups. Diphosphonates 82-84 bone morphogenetic protein 2 Homo sapiens 149-154 26610690-1 2016 An in situ cross-linkable hyaluronan hydrogel functionalized with bisphosphonate (BP) groups allows tunable release of bone morphogenetic protein-2 (BMP-2) determined by the amount of BP groups. Diphosphonates 184-186 bone morphogenetic protein 2 Homo sapiens 119-147 26610690-1 2016 An in situ cross-linkable hyaluronan hydrogel functionalized with bisphosphonate (BP) groups allows tunable release of bone morphogenetic protein-2 (BMP-2) determined by the amount of BP groups. Diphosphonates 184-186 bone morphogenetic protein 2 Homo sapiens 149-154 26610690-2 2016 The high affinity of matrix-anchored BP groups towards BMP-2 permits guided differentiation of entrapped progenitor cells in 3-D cultures. Diphosphonates 37-39 bone morphogenetic protein 2 Homo sapiens 55-60 26721293-10 2016 The presence of Jagged1(+) CTCs was significantly associated with shorter progression-free survival in patients treated with bisphosphonates (P = 0.013). Diphosphonates 125-140 jagged canonical Notch ligand 1 Homo sapiens 16-23 26781029-7 2016 EXPERT OPINION: Notwithstanding their lack of drug-like character, bisphosphonates are still the most advantageous class of inhibitors of the enzymatic activity of farnesyl pyrophosphate synthase. Diphosphonates 67-82 farnesyl diphosphate synthase Homo sapiens 164-195 26757732-10 2016 CONCLUSIONS: The composite biomarker, CAPG and GIPC1 in primary breast tumors, predicted disease outcomes and benefit from zoledronate and may facilitate patient selection for adjuvant bisphosphonate treatment. Diphosphonates 185-199 capping actin protein, gelsolin like Homo sapiens 38-42 26757732-10 2016 CONCLUSIONS: The composite biomarker, CAPG and GIPC1 in primary breast tumors, predicted disease outcomes and benefit from zoledronate and may facilitate patient selection for adjuvant bisphosphonate treatment. Diphosphonates 185-199 GIPC PDZ domain containing family member 1 Homo sapiens 47-52 26608686-0 2016 Numb chin syndrome as initial manifestation of bisphosphonate-related osteomyelitis of the jaw and methotrexate-associated lymphoproliferative disorders: a rare case. Diphosphonates 47-61 NUMB endocytic adaptor protein Homo sapiens 0-4 27252739-3 2016 RESULTS: In drug-naive group (not received osteoporosis medications before the administration, n=70), the concomitant RLX or BP with ELD significantly decreased levels of TRACP-5b without severe suppression. Diphosphonates 125-127 acid phosphatase 5, tartrate resistant Homo sapiens 171-179 27252739-5 2016 CONCLUSION: ELD combined with RLX or BP administered for 6 months to postmenopausal women with osteoporosis who were drug-naive or who had switched medications significantly reduced and maintained TRACP-5b values within the reference range. Diphosphonates 37-39 acid phosphatase 5, tartrate resistant Homo sapiens 197-205 26891809-5 2016 Candidate gene studies suggest that some common polymorphisms of the Wnt pathway and farnesyl diphosphate synthase (FDPS), the target enzyme for bisphosphonates, also influence the response to antiresorptives. Diphosphonates 145-160 farnesyl diphosphate synthase Homo sapiens 85-114 26891809-5 2016 Candidate gene studies suggest that some common polymorphisms of the Wnt pathway and farnesyl diphosphate synthase (FDPS), the target enzyme for bisphosphonates, also influence the response to antiresorptives. Diphosphonates 145-160 farnesyl diphosphate synthase Homo sapiens 116-120 26763447-9 2016 Collectively, these results suggest that bisphosphonate treatment may be beneficial by a dual effect for preventing ectopic soft tissue mineralization while correcting decreased bone mineralization in generalized arterial calcification of infancy caused by ENPP1 mutations. Diphosphonates 41-55 ectonucleotide pyrophosphatase/phosphodiesterase 1 Mus musculus 257-262 27095621-0 2015 Effect of Bisphosphonates on the Levels of Rankl and Opg in Gingival Crevicular Fluid of Patients With Periodontal Disease and Post-menopausal Osteoporosis. Diphosphonates 10-25 TNF superfamily member 11 Homo sapiens 43-48 26967224-9 2016 Bisphosphonate use was more common among people without AD who had comorbidities, asthma/COPD, or rheumatoid arthritis compared with users with AD. Diphosphonates 0-14 COPD Homo sapiens 89-93 27095621-7 2015 The aim of this study was to evaluate the levels of RANKL, OPG and their relationship in gingival crevicular fluid (GCF) in patients with periodontal disease and postmenopausal osteoporosis/ osteopenia in relation to consumption of bisphosphonates. Diphosphonates 232-247 TNF superfamily member 11 Homo sapiens 52-57 26457482-3 2015 However, bisphosphonate bone affinity is often considered too strong and cannot be significantly modulated without losing activity on the enzymatic target, farnesyl pyrophosphate synthase (FPPS). Diphosphonates 9-23 farnesyl diphosphate synthase Homo sapiens 156-187 26445021-9 2015 At variance, osteoblast production of alkaline phosphatase and type I pro-collagen were promoted by the presence of bisphosphonate, which also decreased the production of interleukin 6. Diphosphonates 116-130 collagen type I alpha 2 chain Homo sapiens 63-82 26445021-9 2015 At variance, osteoblast production of alkaline phosphatase and type I pro-collagen were promoted by the presence of bisphosphonate, which also decreased the production of interleukin 6. Diphosphonates 116-130 interleukin 6 Homo sapiens 171-184 26081624-0 2015 Bisphosphonate Induces Osteonecrosis of the Jaw in Diabetic Mice via NLRP3/Caspase-1-Dependent IL-1beta Mechanism. Diphosphonates 0-14 NLR family, pyrin domain containing 3 Mus musculus 69-74 26081624-0 2015 Bisphosphonate Induces Osteonecrosis of the Jaw in Diabetic Mice via NLRP3/Caspase-1-Dependent IL-1beta Mechanism. Diphosphonates 0-14 caspase 1 Mus musculus 75-84 26081624-0 2015 Bisphosphonate Induces Osteonecrosis of the Jaw in Diabetic Mice via NLRP3/Caspase-1-Dependent IL-1beta Mechanism. Diphosphonates 0-14 interleukin 1 beta Mus musculus 95-103 26081624-8 2015 Systemic treatment of mice with zoledronate (Zol), a nitrogen-containing bisphosphonate, resulted in a 1.86- and 1.63-fold increase in NLRP3/caspase-1-dependent IL-1beta secretion by db/+ and db/db BMDMs, respectively, compared with BMDMs derived from nontreated mice (p < 0.001). Diphosphonates 73-87 NLR family, pyrin domain containing 3 Mus musculus 135-140 26081624-8 2015 Systemic treatment of mice with zoledronate (Zol), a nitrogen-containing bisphosphonate, resulted in a 1.86- and 1.63-fold increase in NLRP3/caspase-1-dependent IL-1beta secretion by db/+ and db/db BMDMs, respectively, compared with BMDMs derived from nontreated mice (p < 0.001). Diphosphonates 73-87 caspase 1 Mus musculus 141-150 26081624-8 2015 Systemic treatment of mice with zoledronate (Zol), a nitrogen-containing bisphosphonate, resulted in a 1.86- and 1.63-fold increase in NLRP3/caspase-1-dependent IL-1beta secretion by db/+ and db/db BMDMs, respectively, compared with BMDMs derived from nontreated mice (p < 0.001). Diphosphonates 73-87 interleukin 1 beta Mus musculus 161-169 26457482-3 2015 However, bisphosphonate bone affinity is often considered too strong and cannot be significantly modulated without losing activity on the enzymatic target, farnesyl pyrophosphate synthase (FPPS). Diphosphonates 9-23 farnesyl diphosphate synthase Homo sapiens 189-193 26697449-0 2015 Lipophilic bisphosphonates plus rapamycin: a deadly combination for KRAS-mutated lung adenocarcinoma. Diphosphonates 11-26 KRAS proto-oncogene, GTPase Homo sapiens 68-72 26392134-0 2015 Successful long-term mandibular reconstruction and rehabilitation using non-vascularised autologous bone graft and recombinant human BMP-7 with subsequent endosseous implant in a patient with bisphosphonate-related osteonecrosis of the jaw. Diphosphonates 192-206 bone morphogenetic protein 7 Homo sapiens 133-138 26381451-2 2015 Currently available anti-FPPS drugs are active-site-directed bisphosphonate inhibitors, the peculiar pharmacological profile of which is inadequate for therapeutic indications beyond bone diseases. Diphosphonates 61-75 farnesyl diphosphate synthase Homo sapiens 25-29 26381451-0 2015 Discovery of Novel Allosteric Non-Bisphosphonate Inhibitors of Farnesyl Pyrophosphate Synthase by Integrated Lead Finding. Diphosphonates 34-48 farnesyl diphosphate synthase Homo sapiens 63-94 26381451-3 2015 The recent discovery of an allosteric binding site has paved the way toward the development of novel non-bisphosphonate FPPS inhibitors with broader therapeutic potential, notably as immunomodulators in oncology. Diphosphonates 105-119 farnesyl diphosphate synthase Homo sapiens 120-124 26337218-1 2015 Denosumab, a monoclonal antibody against the receptor activator for nuclear factor-kappa B ligand (RANKL), is a recently approved antiresorptive drug that suppresses osteoclast formation by targeting preosteclasts, in contrast to the traditional antiresorptive bisphosphonates that target mature osteoclasts. Diphosphonates 261-276 TNF superfamily member 11 Homo sapiens 45-97 26614482-7 2015 We demonstrated that microinjury to osteocyte networks being treated with bisphosphonates modulates receptor activator of nuclear factor kappa-B ligand and osteoprotegerin activity, and subsequently osteoclastogenesis. Diphosphonates 74-89 TNF superfamily member 11 Homo sapiens 100-151 26614482-7 2015 We demonstrated that microinjury to osteocyte networks being treated with bisphosphonates modulates receptor activator of nuclear factor kappa-B ligand and osteoprotegerin activity, and subsequently osteoclastogenesis. Diphosphonates 74-89 TNF receptor superfamily member 11b Homo sapiens 156-171 26817293-4 2015 PDB is diagnosed on plain radiograph, the extent of disease is delineated by radionuclide bone imaging, the degree of activity is quantified biochemically, and it is treated with a nitrogen-containing bisphosphonate, most effectively by a single intravenous infusion of zoledronate 5mg. Diphosphonates 201-215 PDB1 Homo sapiens 0-3 26337218-1 2015 Denosumab, a monoclonal antibody against the receptor activator for nuclear factor-kappa B ligand (RANKL), is a recently approved antiresorptive drug that suppresses osteoclast formation by targeting preosteclasts, in contrast to the traditional antiresorptive bisphosphonates that target mature osteoclasts. Diphosphonates 261-276 TNF superfamily member 11 Homo sapiens 99-104 26399387-0 2015 A highly sensitive prenylation assay reveals in vivo effects of bisphosphonate drug on the Rab prenylome of macrophages outside the skeleton. Diphosphonates 64-78 RAB11A, member RAS oncogene family Mus musculus 91-94 26415604-1 2015 OBJECTIVES: To measure the effect of proton pump inhibitors (PPIs), with and without concurrent bisphosphonates, on parathyroid hormone (PTH), vitamin D, and calcium. Diphosphonates 96-111 parathyroid hormone Homo sapiens 116-135 25916730-10 2015 CONCLUSIONS: A down-regulated expression of Casp8 compared with controls was observed (p = .014) in patients treated with bisphosphonates. Diphosphonates 122-137 caspase 8 Homo sapiens 44-49 26027865-0 2015 Adipose-derived stem cells and platelet-rich plasma for preventive treatment of bisphosphonate-related osteonecrosis of the jaw in a murine model. Diphosphonates 80-94 WD and tetratricopeptide repeats 1 Mus musculus 0-7 26086871-1 2015 OBJECTIVES: The purpose of this study was to evaluate the association between vascular endothelial growth factor (VEGF) polymorphisms and bisphosphonate-related osteonecrosis of the jaw (BRONJ) in the Korean population. Diphosphonates 138-152 vascular endothelial growth factor A Homo sapiens 78-112 26086871-1 2015 OBJECTIVES: The purpose of this study was to evaluate the association between vascular endothelial growth factor (VEGF) polymorphisms and bisphosphonate-related osteonecrosis of the jaw (BRONJ) in the Korean population. Diphosphonates 138-152 vascular endothelial growth factor A Homo sapiens 114-118 25863230-1 2015 PURPOSE: The clinical significance of bone turnover marker C-terminal cross-linking telopeptide (CTX) levels less than 150 pg/mL among recipients of oral bisphosphonate (OBP) medications who develop osteonecrosis of the jaws (MRONJ) after exodontia is unclear. Diphosphonates 154-168 cytochrome P450 family 27 subfamily A member 1 Homo sapiens 97-100 26314394-0 2015 Protonation State and Hydration of Bisphosphonate Bound to Farnesyl Pyrophosphate Synthase. Diphosphonates 35-49 farnesyl diphosphate synthase Homo sapiens 59-90 26154398-4 2015 The results of this study show structural changes in the eye and mandible as well as biochemical changes including the up-regulation of VEGF in response to the bisphosphonate-associated ischemia. Diphosphonates 160-174 vascular endothelial growth factor A Rattus norvegicus 136-140 25944731-2 2015 Compared with placebo, bisphosphonates could reduce the risk of vertebral and non-vertebral fractures, reduce bone-specific alkaline phosphatase (BSAP) and C-terminal telopeptide of type I collagen (CTX), and increase bone mineral density (BMD). Diphosphonates 23-38 paired box 5 Homo sapiens 110-144 25944731-2 2015 Compared with placebo, bisphosphonates could reduce the risk of vertebral and non-vertebral fractures, reduce bone-specific alkaline phosphatase (BSAP) and C-terminal telopeptide of type I collagen (CTX), and increase bone mineral density (BMD). Diphosphonates 23-38 paired box 5 Homo sapiens 146-150 25944731-2 2015 Compared with placebo, bisphosphonates could reduce the risk of vertebral and non-vertebral fractures, reduce bone-specific alkaline phosphatase (BSAP) and C-terminal telopeptide of type I collagen (CTX), and increase bone mineral density (BMD). Diphosphonates 23-38 cytochrome P450 family 27 subfamily A member 1 Homo sapiens 199-202 25944731-9 2015 The efficacy of bisphosphonates on reducing BSAP [MD (95 % CI) -24.41 (-26.19, -22.62), P < 0.01) and CTX [MD (95 % CI) -34.51 (-41.03, -27.98), P < 0.01)] was significant. Diphosphonates 16-31 paired box 5 Homo sapiens 44-48 25944731-9 2015 The efficacy of bisphosphonates on reducing BSAP [MD (95 % CI) -24.41 (-26.19, -22.62), P < 0.01) and CTX [MD (95 % CI) -34.51 (-41.03, -27.98), P < 0.01)] was significant. Diphosphonates 16-31 cytochrome P450 family 27 subfamily A member 1 Homo sapiens 105-108 25944731-12 2015 CONCLUSION: Compared with placebo, bisphosphonates could decrease the risk of vertebral and non-vertebral fractures, reduce BSAP and CTX, and increase BMD in men with osteoporosis. Diphosphonates 35-50 paired box 5 Homo sapiens 124-128 25944731-12 2015 CONCLUSION: Compared with placebo, bisphosphonates could decrease the risk of vertebral and non-vertebral fractures, reduce BSAP and CTX, and increase BMD in men with osteoporosis. Diphosphonates 35-50 cytochrome P450 family 27 subfamily A member 1 Homo sapiens 133-136 23651067-2 2015 We hypothesized that the cyclooxygenase (COX)-2 inhibitor, meloxicam, with the bisphosphonate, zoledronic acid (ZOL), would inhibit tumour growth, osteolysis and invasion in feline OSCC xenografts in mice. Diphosphonates 79-93 cytochrome c oxidase II, mitochondrial Mus musculus 25-47 25534961-10 2015 The changes in levels of ALP correlated well with the changes in BAP levels before and after bisphosphonate therapy. Diphosphonates 93-107 alkaline phosphatase, placental Homo sapiens 25-28 25534961-12 2015 DISCUSSION: Bisphosphonate treatment lowered ALP levels, and this decrease was strongly correlated with a decrease in BAP. Diphosphonates 12-26 alkaline phosphatase, placental Homo sapiens 45-48 25534961-12 2015 DISCUSSION: Bisphosphonate treatment lowered ALP levels, and this decrease was strongly correlated with a decrease in BAP. Diphosphonates 12-26 prohibitin 2 Homo sapiens 118-121 26222035-4 2015 We covalently bonded BP to functionalised HA (HA-BP) and found that HA-BP conjugates were highly specific to osteoclastic cells and reduced mature osteoclast numbers significantly more than free BP. Diphosphonates 21-23 hyaluronan binding protein 2 Homo sapiens 46-51 26240717-3 2015 OVERVIEW OF LITERATURE: We reported that daily subcutaneous injection of teriparatide (parathyroid hormone) significantly improved bone union after instrumented lumbar posterolateral fusion (PLF) in women with postmenopausal osteoporosis when compared with oral administration of bisphosphonate. Diphosphonates 280-294 parathyroid hormone Homo sapiens 87-106 26222035-4 2015 We covalently bonded BP to functionalised HA (HA-BP) and found that HA-BP conjugates were highly specific to osteoclastic cells and reduced mature osteoclast numbers significantly more than free BP. Diphosphonates 21-23 hyaluronan binding protein 2 Homo sapiens 68-73 26085098-3 2015 The traditional bisphosphonate (BP) alendronate (Aln) or IG9402, a BP analog that does not inhibit resorption, prevented the increase in osteocyte apoptosis and osteocytic RANKL expression. Diphosphonates 16-30 tumor necrosis factor (ligand) superfamily, member 11 Mus musculus 172-177 26073627-6 2015 The free acid form of a PyrBP and a known bisphosphonate inhibitor of vertebrate FPPS, alendronate, had little to no effect on larval M. sexta; however, the topical application of more lipophilic ester PyrBPs caused decreased growth, incomplete larval molting, cuticle darkening at the site of application, and for those insects that survived, the formation of larval-pupal hybrids. Diphosphonates 42-56 Farnesyl pyrophosphate synthase Drosophila melanogaster 81-85 26085098-3 2015 The traditional bisphosphonate (BP) alendronate (Aln) or IG9402, a BP analog that does not inhibit resorption, prevented the increase in osteocyte apoptosis and osteocytic RANKL expression. Diphosphonates 32-34 tumor necrosis factor (ligand) superfamily, member 11 Mus musculus 172-177 26161381-11 2015 CONCLUSION: Low concentration bisphosphonate and rhBMP-2 have synergic effect on bone regeneration and this is result from the decreased activity of RANKL of osteoblast. Diphosphonates 30-44 TNF superfamily member 11 Rattus norvegicus 149-154 25945831-1 2015 The in vivo hydrolytic pathway of a dual-function bone-targeting EP4 receptor agonist-bisphosphonate pro-drug was deduced from radiolabeling experiments. Diphosphonates 86-100 prostaglandin E receptor 4 Rattus norvegicus 65-68 25467232-0 2015 BRONJ-related jaw bone is associated with increased Dlx-5 and suppressed osteopontin-implication in the site-specific alteration of angiogenesis and bone turnover by bisphosphonates. Diphosphonates 166-181 secreted phosphoprotein 1 Homo sapiens 73-84 25963272-4 2015 Newer antiresorptive therapies, in the form of denosumab and cathepsin K inhibitors, might increase efficacy and possibly circumvent some of the safety concerns associated with bisphosphonate use (for example, gastrointestinal and renal complications). Diphosphonates 177-191 cathepsin K Homo sapiens 61-72 26037791-13 2015 After starting treatment with bisphosphonate, there was moderate to strong correlation with disease activity with all markers except bone ALP (correlation coefficients ranging from 0.43 to 0.70). Diphosphonates 30-44 ATHS Homo sapiens 138-141 25989268-3 2015 Time-dependent Cox regression models investigated colorectal cancer-specific mortality in post-diagnostic bisphosphonate users. Diphosphonates 106-120 cytochrome c oxidase subunit 8A Homo sapiens 15-18 25613175-5 2015 Using a fluorescently-labeled bisphosphonate, we show that early binding kinetics monitored in vivo using fluorescent molecular tomography (FMT) can monitor changes in bone metabolism in response to bone loss, stimulated by ovariectomy (OVX), or bone gain, resulting from treatment with the anabolic bone agent parathyroid hormone (PTH), and is capable of distinguishing different, metabolically distinct skeletal sites. Diphosphonates 30-44 parathyroid hormone Mus musculus 311-330 25164156-7 2015 In general, a significantly decreased expression of CD54, CD80, and HLA-DR membrane antigens was observed after 24 h of treatment with each nitrogen-containing bisphosphonate (p < 0.05), but there was no significant difference in phagocytic activity versus controls. Diphosphonates 160-174 intercellular adhesion molecule 1 Homo sapiens 52-56 25164156-7 2015 In general, a significantly decreased expression of CD54, CD80, and HLA-DR membrane antigens was observed after 24 h of treatment with each nitrogen-containing bisphosphonate (p < 0.05), but there was no significant difference in phagocytic activity versus controls. Diphosphonates 160-174 CD80 molecule Homo sapiens 58-62 26101727-1 2015 Although kidney injury associated with intravenous bisphosphonate therapy is well documented, there are very few reported instances of oral bisphosphonate therapy leading to focal segmental glomerulosclerosis (FSGS) and kidney failure. Diphosphonates 140-154 actinin alpha 4 Homo sapiens 210-214 25338093-10 2015 Since increased bone turnover is the primary contributor of osteoporosis in NF1, antiresorptive agents such as bisphosphonates can be considered for treatment. Diphosphonates 111-126 neurofibromin 1 Homo sapiens 76-79 25532478-11 2015 In conclusion as previously observed for bisphosphonates (ZOL), a RANKL-blocking antibody induced a transient arrest in long bone and skull bone growth and a blockage of tooth eruption with however disparities between mouse strains with regard to this last effect. Diphosphonates 41-56 tumor necrosis factor (ligand) superfamily, member 11 Mus musculus 66-71 26101727-4 2015 This case report and the literature review highlight the fact that oral bisphosphonates may be associated with a risk of developing FSGS. Diphosphonates 72-87 actinin alpha 4 Homo sapiens 132-136 25764158-1 2015 The present study investigated the effect of two single nucleotide polymorphisms (SNPs) of the vitamin D receptor (VDR) gene, rs1544410 A/G and rs2228570 C/T, in modulating bone mineral density (BMD) and the response to treatment with bisphosphonates or strontium ranelate in postmenopausal osteoporosis (PMO). Diphosphonates 235-250 vitamin D receptor Homo sapiens 95-113 25764158-1 2015 The present study investigated the effect of two single nucleotide polymorphisms (SNPs) of the vitamin D receptor (VDR) gene, rs1544410 A/G and rs2228570 C/T, in modulating bone mineral density (BMD) and the response to treatment with bisphosphonates or strontium ranelate in postmenopausal osteoporosis (PMO). Diphosphonates 235-250 vitamin D receptor Homo sapiens 115-118 25573204-2 2015 This study investigated the value of serum YKL-40, previously shown to be associated with radiographic progression of bone destruction, as a predictor for time to clinical progression, i.e. skeletal-related events (SREs), in 230 newly diagnosed patients with multiple myeloma receiving intravenous bisphosphonates. Diphosphonates 298-313 chitinase 3 like 1 Homo sapiens 43-49 25395071-6 2015 At baseline, sema4D and plexin-B1 levels were higher in patients pre-treated with bisphosphonates compared to naive ones (p < 0.001 and p = 0.001, respectively). Diphosphonates 82-97 semaphorin 4D Homo sapiens 13-19 25395071-6 2015 At baseline, sema4D and plexin-B1 levels were higher in patients pre-treated with bisphosphonates compared to naive ones (p < 0.001 and p = 0.001, respectively). Diphosphonates 82-97 plexin B1 Homo sapiens 24-33 25395071-8 2015 CONCLUSIONS: Sema4D levels are independently associated with previous bisphosphonate treatment, intact parathyroid hormone and 25(OH)D levels. Diphosphonates 70-84 semaphorin 4D Homo sapiens 13-19 25349053-12 2015 In sub-cohorts, compared to none, lowest cumulative bisphosphonate use (one to nine pills) was associated with higher risk of endoscopy (OR 1.11, 95% CI 1.08-1.14) and antacid initiation (OR 1.13, 95% CI 1.10-1.16); higher intensity conferred no increased risk. Diphosphonates 52-66 olfactory receptor family 7 subfamily E member 10 pseudogene Homo sapiens 137-144 25349053-12 2015 In sub-cohorts, compared to none, lowest cumulative bisphosphonate use (one to nine pills) was associated with higher risk of endoscopy (OR 1.11, 95% CI 1.08-1.14) and antacid initiation (OR 1.13, 95% CI 1.10-1.16); higher intensity conferred no increased risk. Diphosphonates 52-66 olfactory receptor family 7 subfamily E member 12 pseudogene Homo sapiens 188-195 25815158-4 2015 With the bisphosphonate inhibitor 8, two molecules bind to Trypanosoma brucei FPPS, one molecule in the allylic site (S1) and the other close to S2, the first observation of two bisphosphonate molecules bound to FPPS. Diphosphonates 9-23 farnesyl diphosphate synthase Homo sapiens 78-82 25815158-4 2015 With the bisphosphonate inhibitor 8, two molecules bind to Trypanosoma brucei FPPS, one molecule in the allylic site (S1) and the other close to S2, the first observation of two bisphosphonate molecules bound to FPPS. Diphosphonates 178-192 farnesyl diphosphate synthase Homo sapiens 78-82 26297076-7 2015 RESULTS: MPR over 5 years was 20.8 and 60.9 % for daily and weekly BPs (p < 0.001), respectively. Diphosphonates 67-70 progesterone receptor membrane component 1 Homo sapiens 9-12 26297076-8 2015 MPR over 1 year was 38.6, 70.6, and 77.7 % for daily, weekly, and monthly BPs (P < 0.001), respectively. Diphosphonates 74-77 progesterone receptor membrane component 1 Homo sapiens 0-3 25535905-7 2015 After bisphosphonate treatment, BAP significantly decreased to 18.1 +- 7.2 U/L at 3 years (p < 0.001). Diphosphonates 6-20 prohibitin 2 Homo sapiens 32-35 25630225-1 2015 In order to explore the interactions of bisphosphonate ligands with the active site and an allosteric pocket of the human farnesyl pyrophosphate synthase (hFPPS), substituted indole and azabenzimidazole bisphosphonates were designed as chameleon ligands. Diphosphonates 40-54 farnesyl diphosphate synthase Homo sapiens 122-153 25630225-1 2015 In order to explore the interactions of bisphosphonate ligands with the active site and an allosteric pocket of the human farnesyl pyrophosphate synthase (hFPPS), substituted indole and azabenzimidazole bisphosphonates were designed as chameleon ligands. Diphosphonates 40-54 farnesyl diphosphate synthase Homo sapiens 155-160 25820558-0 2015 RANK/RANKL/OPG signaling pathways in necrotic jaw bone from bisphosphonate-treated subjects. Diphosphonates 60-74 TNF superfamily member 11 Homo sapiens 5-10 25820558-0 2015 RANK/RANKL/OPG signaling pathways in necrotic jaw bone from bisphosphonate-treated subjects. Diphosphonates 60-74 basic transcription factor 3 pseudogene 11 Homo sapiens 11-14 25820558-3 2015 The aim of the present study was to investigate the role of RANK/RANKL/OPG signaling pathway and, in parallel, to evaluate angiogenic and matrix mineralization processes in jaw bone necrotic samples obtained from bisphosphonate-treated subjects with established ONJ. Diphosphonates 213-227 TNF superfamily member 11 Homo sapiens 65-70 25607347-0 2015 The effects of bisphosphonates on ectopic soft tissue mineralization caused by mutations in the ABCC6 gene. Diphosphonates 15-30 ATP-binding cassette, sub-family C (CFTR/MRP), member 6 Mus musculus 96-101 25607347-4 2015 We explored the potential efficacy of bisphosphonates to prevent ectopic calcification caused by ABCC6 mutations by feeding Abcc6(-/-) mice with diet containing etidronate disodium (ETD) or alendronate sodium trihydrate (AST) in quantities corresponding to 1x, 5x, or 12x of the doses used to treat osteoporosis in humans. Diphosphonates 38-53 ATP-binding cassette, sub-family C (CFTR/MRP), member 6 Mus musculus 97-102 25607347-6 2015 We found that ETD, but not AST, at the 12x dosage, significantly reduced mineralization, suggesting that selected bisphosphonates may be helpful for prevention of mineral deposits in PXE and GACI caused by mutations in the ABCC6 gene, when combined with careful monitoring of efficacy and potential side-effects. Diphosphonates 114-129 ATP-binding cassette, sub-family C (CFTR/MRP), member 6 Mus musculus 223-228 26118456-3 2015 Gp2 received bisphosphonates following standard practice. Diphosphonates 13-28 glycoprotein 2 Homo sapiens 0-3 25746831-1 2015 INTRODUCTION: Zoledronic acid (ZA), a bisphosphonate, increases the levels of cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha), and reactive oxygen species (ROS) in subjects without cancer. Diphosphonates 38-52 interleukin 6 Rattus norvegicus 97-110 25746831-1 2015 INTRODUCTION: Zoledronic acid (ZA), a bisphosphonate, increases the levels of cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha), and reactive oxygen species (ROS) in subjects without cancer. Diphosphonates 38-52 interleukin 6 Rattus norvegicus 112-116 25746831-1 2015 INTRODUCTION: Zoledronic acid (ZA), a bisphosphonate, increases the levels of cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha), and reactive oxygen species (ROS) in subjects without cancer. Diphosphonates 38-52 tumor necrosis factor Rattus norvegicus 122-149 25746831-1 2015 INTRODUCTION: Zoledronic acid (ZA), a bisphosphonate, increases the levels of cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha), and reactive oxygen species (ROS) in subjects without cancer. Diphosphonates 38-52 tumor necrosis factor Rattus norvegicus 151-160 25453078-2 2014 Having shown that bisphosphonates, a class of drugs used widely for the therapy of osteoporosis and metastatic bone disease, reduce cancer cell viability by targeting HER1, we explored their potential utility in the prevention and therapy of HER-driven cancers. Diphosphonates 18-33 epidermal growth factor receptor Homo sapiens 167-171 25453078-3 2014 We show that bisphosphonates inhibit colony formation by HER1(DeltaE746-A750)-driven HCC827 NSCLCs and HER1(wt)-expressing MB231 triple negative breast cancers, but not by HER(low)-SW620 colon cancers. Diphosphonates 13-28 epidermal growth factor receptor Homo sapiens 103-107 25453078-3 2014 We show that bisphosphonates inhibit colony formation by HER1(DeltaE746-A750)-driven HCC827 NSCLCs and HER1(wt)-expressing MB231 triple negative breast cancers, but not by HER(low)-SW620 colon cancers. Diphosphonates 13-28 epidermal growth factor receptor Homo sapiens 57-61 25453078-7 2014 In silico docking, together with molecular dynamics and anisotropic network modeling, showed that bisphosphonates bind to TKIs within the HER1 kinase domain. Diphosphonates 98-113 epidermal growth factor receptor Homo sapiens 138-142 25453081-3 2014 Using connectivity mapping, we identified human epidermal growth factor receptors (human EGFR or HER) as a potential new molecular entity for bisphosphonate action. Diphosphonates 142-156 epidermal growth factor receptor Homo sapiens 89-93 25628928-6 2015 In this study, we found that bisphosphonates and statins inhibited MIP-1alpha mRNA and MIP-1alpha secretion and suppressed extracellular signal-regulated kinase 1/2 (ERK1/2) and Akt phosphorylation by inhibiting Ras prenylation. Diphosphonates 29-44 C-C motif chemokine ligand 3 Homo sapiens 87-97 25628928-6 2015 In this study, we found that bisphosphonates and statins inhibited MIP-1alpha mRNA and MIP-1alpha secretion and suppressed extracellular signal-regulated kinase 1/2 (ERK1/2) and Akt phosphorylation by inhibiting Ras prenylation. Diphosphonates 29-44 mitogen-activated protein kinase 1 Homo sapiens 123-164 25628928-0 2015 Bisphosphonates and statins inhibit expression and secretion of MIP-1alpha via suppression of Ras/MEK/ERK/AML-1A and Ras/PI3K/Akt/AML-1A pathways. Diphosphonates 0-15 C-C motif chemokine ligand 3 Homo sapiens 64-74 25628928-6 2015 In this study, we found that bisphosphonates and statins inhibited MIP-1alpha mRNA and MIP-1alpha secretion and suppressed extracellular signal-regulated kinase 1/2 (ERK1/2) and Akt phosphorylation by inhibiting Ras prenylation. Diphosphonates 29-44 mitogen-activated protein kinase 3 Homo sapiens 166-172 25628928-0 2015 Bisphosphonates and statins inhibit expression and secretion of MIP-1alpha via suppression of Ras/MEK/ERK/AML-1A and Ras/PI3K/Akt/AML-1A pathways. Diphosphonates 0-15 mitogen-activated protein kinase kinase 7 Homo sapiens 98-101 25628928-6 2015 In this study, we found that bisphosphonates and statins inhibited MIP-1alpha mRNA and MIP-1alpha secretion and suppressed extracellular signal-regulated kinase 1/2 (ERK1/2) and Akt phosphorylation by inhibiting Ras prenylation. Diphosphonates 29-44 AKT serine/threonine kinase 1 Homo sapiens 178-181 25628928-0 2015 Bisphosphonates and statins inhibit expression and secretion of MIP-1alpha via suppression of Ras/MEK/ERK/AML-1A and Ras/PI3K/Akt/AML-1A pathways. Diphosphonates 0-15 mitogen-activated protein kinase 1 Homo sapiens 102-105 25628928-0 2015 Bisphosphonates and statins inhibit expression and secretion of MIP-1alpha via suppression of Ras/MEK/ERK/AML-1A and Ras/PI3K/Akt/AML-1A pathways. Diphosphonates 0-15 AKT serine/threonine kinase 1 Homo sapiens 126-129 25628928-6 2015 In this study, we found that bisphosphonates and statins inhibited MIP-1alpha mRNA and MIP-1alpha secretion and suppressed extracellular signal-regulated kinase 1/2 (ERK1/2) and Akt phosphorylation by inhibiting Ras prenylation. Diphosphonates 29-44 C-C motif chemokine ligand 3 Homo sapiens 67-77 25628928-7 2015 Moreover, bisphosphonates and statins suppressed the expression of acute myeloid leukemia-1A (AML-1A) mRNA, a MIP-1alpha transcription factor. Diphosphonates 10-25 C-C motif chemokine ligand 3 Homo sapiens 110-120 25628928-8 2015 These results indicate that bisphosphonates and statins suppress the Ras/mitogen-activated protein kinase kinase/ERK/AML-1A and Ras/phosphatidylinositol-3 kinase/Akt/AML-1A pathways, thereby inhibiting MIP-1alpha secretion by MM cells. Diphosphonates 28-43 mitogen-activated protein kinase 1 Homo sapiens 113-116 25628928-8 2015 These results indicate that bisphosphonates and statins suppress the Ras/mitogen-activated protein kinase kinase/ERK/AML-1A and Ras/phosphatidylinositol-3 kinase/Akt/AML-1A pathways, thereby inhibiting MIP-1alpha secretion by MM cells. Diphosphonates 28-43 AKT serine/threonine kinase 1 Homo sapiens 162-165 25628928-8 2015 These results indicate that bisphosphonates and statins suppress the Ras/mitogen-activated protein kinase kinase/ERK/AML-1A and Ras/phosphatidylinositol-3 kinase/Akt/AML-1A pathways, thereby inhibiting MIP-1alpha secretion by MM cells. Diphosphonates 28-43 C-C motif chemokine ligand 3 Homo sapiens 202-212 25496233-8 2014 RESULTS: Treatment of MDA-MB-231 with BP induced caspase 3/7 activity, with zoledronic acid being the most effective. Diphosphonates 38-40 caspase 3 Homo sapiens 49-58 25496233-10 2014 Co-treatment with probenecid enhanced BP effects on cell viability, IPP/ApppI accumulation as measurable in MCF-7 and T47D cells, caspase 3/7 activity and target gene expression. Diphosphonates 38-40 caspase 3 Homo sapiens 130-139 25496233-12 2014 CONCLUSIONS: In summary, we demonstrate effects of various bisphosphonates on caspase 3/7 activity, cell viability and expression of tumor suppressor genes in breast cancer cells. Diphosphonates 59-74 caspase 3 Homo sapiens 78-87 25501755-5 2014 Pulmonary metastasis was diagnosed at 4 years after the initial surgery.Despite treatment with intravenous bisphosphonates, her calcium and parathyroid hormone (PTH) levels remained elevated, and leg amputation was performed following the development of arteriosclerosis obliterans at 6 years after the initial neck resection. Diphosphonates 107-122 parathyroid hormone Homo sapiens 140-159 25551094-0 2014 Effect of recombinant human bone morphogenetic protein-2 on bisphosphonate-treated osteoblasts. Diphosphonates 60-74 bone morphogenetic protein 2 Homo sapiens 28-56 25146376-2 2014 Depletion of brain PVM in SIV-infected monkeys by intrathecal injection of liposome-encapsulated bisphosphonates eliminated CD206-expressing cells in the brain, confirming their perivascular location and phagocytic capacity. Diphosphonates 97-112 mannose receptor C-type 1 Homo sapiens 124-129 25501755-5 2014 Pulmonary metastasis was diagnosed at 4 years after the initial surgery.Despite treatment with intravenous bisphosphonates, her calcium and parathyroid hormone (PTH) levels remained elevated, and leg amputation was performed following the development of arteriosclerosis obliterans at 6 years after the initial neck resection. Diphosphonates 107-122 parathyroid hormone Homo sapiens 161-164 25411474-6 2014 Bisphosphonate treatment of cells initiated autophagy but was ultimately unsuccessful and led to p62 accumulation and concomitant nuclear factor kappaB (NF-kappaB) activation, resulting in dampened efficacy in vivo. Diphosphonates 0-14 nuclear factor kappa B subunit 1 Homo sapiens 145-151 25411474-6 2014 Bisphosphonate treatment of cells initiated autophagy but was ultimately unsuccessful and led to p62 accumulation and concomitant nuclear factor kappaB (NF-kappaB) activation, resulting in dampened efficacy in vivo. Diphosphonates 0-14 nuclear factor kappa B subunit 1 Homo sapiens 153-162 25411474-8 2014 Overall, these results suggest that using lipophilic bisphosphonates in combination with rapamycin may provide an effective strategy for targeting lung adenocarcinomas harboring KRAS mutations. Diphosphonates 53-68 KRAS proto-oncogene, GTPase Homo sapiens 178-182 25173134-1 2014 Drug-induced osteonecrosis of the jaw (ONJ) is a detrimental intraoral lesion that often occurs after dental-related interventions in patients undergoing treatment with bisphosphonates or denosumab, the neutralizing human anti-receptor activator of NF-kappaB ligand (RANKL) antibody (Ab). Diphosphonates 169-184 TNF superfamily member 11 Homo sapiens 222-265 25173134-1 2014 Drug-induced osteonecrosis of the jaw (ONJ) is a detrimental intraoral lesion that often occurs after dental-related interventions in patients undergoing treatment with bisphosphonates or denosumab, the neutralizing human anti-receptor activator of NF-kappaB ligand (RANKL) antibody (Ab). Diphosphonates 169-184 TNF superfamily member 11 Homo sapiens 267-272 25473406-2 2014 Collapsing focal segmental glomerulosclerosis (FSGS) is known to occur uncommonly with exposure to bisphosphonates, specifically pamidronate and alendronate; it has rarely and equivocally been reported with zoledronate therapy. Diphosphonates 99-114 actinin alpha 4 Homo sapiens 11-45 25473406-2 2014 Collapsing focal segmental glomerulosclerosis (FSGS) is known to occur uncommonly with exposure to bisphosphonates, specifically pamidronate and alendronate; it has rarely and equivocally been reported with zoledronate therapy. Diphosphonates 99-114 actinin alpha 4 Homo sapiens 47-51 25232075-14 2014 CONCLUSIONS: Administration of BMP-2 with bisphosphonate best decreased bone resorption and increased new bone formation during non-weight-bearing treatment of ischemic osteonecrosis in a pig model, but heterotopic ossification is a concern. Diphosphonates 42-56 bone morphogenetic protein 2 Sus scrofa 31-36 25232075-15 2014 CLINICAL RELEVANCE: This preclinical study provides new evidence that BMP-2 with bisphosphonate can effectively prevent the extreme bone loss associated with the non-weight-bearing treatment and increase new bone formation in the femoral head in this animal model of ischemic osteonecrosis. Diphosphonates 81-95 bone morphogenetic protein 2 Sus scrofa 70-75 25411474-0 2014 A combination therapy for KRAS-driven lung adenocarcinomas using lipophilic bisphosphonates and rapamycin. Diphosphonates 76-91 KRAS proto-oncogene, GTPase Homo sapiens 26-30 25411474-5 2014 Lipophilic bisphosphonates inhibit both farnesyl and geranylgeranyldiphosphate synthases, effectively blocking prenylation of KRAS and other small G proteins (heterotrimeric GTP-binding protein, heterotrimeric guanine nucleotide-binding proteins) critical for tumor growth and cell survival. Diphosphonates 11-26 KRAS proto-oncogene, GTPase Homo sapiens 126-130 25411474-6 2014 Bisphosphonate treatment of cells initiated autophagy but was ultimately unsuccessful and led to p62 accumulation and concomitant nuclear factor kappaB (NF-kappaB) activation, resulting in dampened efficacy in vivo. Diphosphonates 0-14 nucleoporin 62 Homo sapiens 97-100 25047677-15 2014 Cox regression showed a reduced risk of revision surgery in bisphosphonate users (hazard ratio 0.41 [95% confidence interval 0.27-0.61]). Diphosphonates 60-74 cytochrome c oxidase subunit 8A Homo sapiens 0-3 25122553-1 2014 Bisphosphonates inhibit osteoclast differentiation/function via inhibition of Rap1A isoprenylation. Diphosphonates 0-15 RAS-related protein 1a Mus musculus 78-83 25314942-8 2014 Meanwhile, after bisphosphonates treatment, bone mineral density, intact parathyroid hormone, and 1,25-dihydroxyvitamin D increased, and serum ionized calcium, urinary deoxypyridinoline decreased compared with the placebo group. Diphosphonates 17-32 parathyroid hormone Homo sapiens 73-92 25003812-2 2014 We compared the effects of two bisphosphonate treatments on two Wnt-inhibitors Sclerostin (SOST) and Dickkopf-related protein 1 (DKK1). Diphosphonates 31-45 sclerostin Homo sapiens 79-89 25003812-2 2014 We compared the effects of two bisphosphonate treatments on two Wnt-inhibitors Sclerostin (SOST) and Dickkopf-related protein 1 (DKK1). Diphosphonates 31-45 sclerostin Homo sapiens 91-95 25003812-2 2014 We compared the effects of two bisphosphonate treatments on two Wnt-inhibitors Sclerostin (SOST) and Dickkopf-related protein 1 (DKK1). Diphosphonates 31-45 dickkopf WNT signaling pathway inhibitor 1 Homo sapiens 101-127 25003812-2 2014 We compared the effects of two bisphosphonate treatments on two Wnt-inhibitors Sclerostin (SOST) and Dickkopf-related protein 1 (DKK1). Diphosphonates 31-45 dickkopf WNT signaling pathway inhibitor 1 Homo sapiens 129-133 25010833-5 2014 Intravenous bisphosphonate treatment of four children with homozygous or compound heterozygous WNT1 mutations was associated with increasing lumbar spine areal bone mineral density z-scores, as measured by dual energy X-ray absorptiometry, but the effect was smaller than what had previously been reported for children with classical osteogenesis imperfecta. Diphosphonates 12-26 Wnt family member 1 Homo sapiens 95-99 25274386-7 2014 Novel pharmaceutical therapy approaches with human monoclonal RANKL antibodies interfere in this osteodestructive process in an inhibitory manner and can represent alternative treatment options just as the osteosupportive therapy with bisphosphonates. Diphosphonates 235-250 TNF superfamily member 11 Homo sapiens 62-67