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Best Practice & Research Clinical Endocrinology & Metabolism
Volume 22, Issue 5
, Pages 831-847
, October 2008
Bisphosphonates: how do they work?
References
- . Bisphosphonates: mechanisms of action and clinical applications. In: Peck WA editors. Bone and mineral research annual 1. Amsterdam: Excerpta Medica; 1982;p. 319–357
- . History of the bisphosphonates: discovery and history of the non medical uses of bisphosphonates. In: Bijvoet OLM, Fleisch HA, Canfield RE, Russell RGG editor. Bisphosphonates on bones. Amsterdam: Elsevier; 1995;p. 111–124
- . The physical chemistry of the diphosphonates-Its relationship to their structural activity. In: Donath A, Courvoisier B editor. Symposium CEMO IV. Nyon Switzerland. Geneva: Editions Medecine est Hygiene; 1982;p. 1–19
- Structural requirements for bisphosphonates actions in vitro. Journal of Bone and Mineral Research. 1994;12:1875–1882
- Binding and antiresorptive properties of heterocycle-containing bisphosphonate analogs: structure-activity relationships. Bone. 1998;23:437–442
- Relative binding affinities of bisphosphonates for human bone and relationship to antiresorptive efficacy. Bone. 2006;38:628–636
- Novel insights into actions of bisphosphonates on bone: differences in interactions with hydroxyapatite. Bone. 2006;38:617–627
- Bisphosphonate binding affinity as assessed by inhibition of carbonated apatite dissolution in vitro. Journal of Biomedical Materials Research. Part A. 2008;85:993–1000
- Mechanisms of action of bisphosphonates: similarities and differences and their potential influence on clinical efficacy. Osteoporosis International. 2008;19:733–759
- Dissociation of binding and antiresorptive properties of hydroxybisphosphonates by substitution of the hydroxyl with an amino group. Journal of Bone and Mineral Research. 1996;11:1492–1497
- Differential effects of aminosubstituted analogs of hydroxy bisphosphonates on the growth of the Dictyostelium discoideum. Journal of Bone and Mineral Research. 1998;13:253–258
- Structure-activity relationships of various bisphosphonates. Calcified Tissue International. 1983;35:87–99
- . New insights into the molecular mechanisms of action of bisphosphonates. Current Pharmaceutical Design. 2003;11:196–214
- . Nitrogen-containig bisphosphonate mechanism of action. Mini Reviews in Medicinal Chemistry. 2004;4:711–719
- Cytosolic entry of bisphosphonate drugs requires acidification of vesicles following fluid-phase endocytosis. Molecular Pharmacology. 2006;69(69):1624–1632
- Visualizing mineral binding and uptake of bisphosphonates by osteoclasts and non-resorbing cells. Bone. 2008;42:848–860
- . From molds and macrophages to mevalonate: a decade of progress in understanding the molecular mode of action of bisphosphonates. Calcified Tissue International. 2004;75:451–461
- . Recent advances in understanding the mechanism of action of bisphosphonates. Current Opinion in Pharmacology. 2006;6:307–312
- Structure-activity relationships for inhibition of pharnesyl diphosphate synthase in vitro and inhibition of bone resorption in vivo by nitrogen-containing bisphosphonates. The Journal of Pharmacology and Experimental Therapeutics. 2001;296:235–242
- A new endogenous ATP analog (ApppI) inhibits the mitochondrial adenine nucleotide translocase (ANT) and is responsible for the apoptosis induced by nitrogen-containing bisphosphonates. British Journal of Pharmacology. 2006;147:437–445
- Prevention of osteocyte and osteoblast apoptosis by bisphosphonates and calcitonin. The Journal of Clinical Investigation. 1999;104:1363–1374
- . Dissociation of the pro-apoptotic effects of bisphosphonates on osteoclasts from their anti-apoptotic effects on osteoblasts/osteocytes with novel analogs. Bone. 2006;39:443–452
- Bisphosphonates and estrogens inhibit osteocyte apoptosis via distinct molecular mechanisms downstream of extracellular signal-regulated kinase activation. The Journal of Biological Chemistry. 2005;280:7317–7325
- Risedronate and alendronate suppress osteocyte apoptosis following cyclic fatigue loading. Bone. 2007;40:1172–1177
- A bisphosphonate analog that lacks anti-remodeling activity prevents osteocyte and osteoblast apoptosis in vivo. Journal of Bone and Mineral Research. 2007;22(Suppl. 1):S4
- Histomorphometric assessment of the long-term effects of alendronate on bone quality and remodeling in patients with osteoporosis. The Journal of Clinical Investigation. 1997;100:1475–1480
- Bone histomorphometric evaluation of pamidronate treatment in clinically manifest osteoporosis. Osteoporosis International. 1999;9:489–493
- Effects of long-term risedronate on bone quality and bone turnover in women with postmenopausal osteoporosis. Bone. 2002;31:620–625
- Histomorphometric evaluation of daily and intermittent oral ibandronate in women with post-menopausal osteoporosis: results from the BONE study. Osteoporosis International. 2004;15:231–237
- Trabecular bone microarchitecture after alendronate treatment of osteoporotic women. Current Medical Research and Opinion. 2005;21:185–194
- Effects of intravenous zoledronic acid once yearly on bone remodeling and bone structure. Journal of Bone and Mineral Research. 2008;23:6–16
- Alendronate increases degree and uniformity of mineralization in cancellous bone and decreases the porosity in cortical bone of osteoporotic women. Bone. 2001;29:185–191
- Alendronate increases bone strength by increasing the mean degree of mineralization of bone tissue in osteoporotic women. Bone. 2000;27:687–694
- The effect of risedronate on bone mineralization as measured by micro-computed tomography with synchrotron radiation: correlation to histomorphometric indices of turnover. Bone. 2005;37:1–9
- Long-term risedronate treatment normalizes mineralization and continues to preserve trabecular architecture: sequential triple biopsy studies with micro-computed tomography. Bone. 2006;39:345–352
- Mineralization status of bone matrix in postmenopausal women during a 10-year alendronate treatment period. Journal of Bone and Mineral Research. 2007;22(Suppl. 1):S129
- Suppressed bone turnover by bisphosphonates increases microdamage accumulation and reduces some biomechanical properties in dog rib. Journal of Bone and Mineral Research. 2000;15:613–620
- Effects of suppressed bone turnover by bisphosphonates on microdamage accumulation and biomechanical properties in clinically relevant skeletal sites in beagles. Bone. 2001;28:524–531
- Long-term treatment of incadronate disodium accumulates microdamage but improves trabecular bone microarchitecture in dog vertebra. Journal of Bone and Mineral Research. 2003;18:512–520
- Alterations in canine vertebral bone turnover, microdamage accumulation, and biomechanical properties following 1-year treatment with clinical treatment doses of risedronate or alendronate. Bone. 2006;39:872–879
- Microcrack frequency and bone remodeling in postmenopausal osteoporotic women on long-term bisphosphonates: a bone biopsy study. Journal of Bone and Mineral Research. 2007;22:1502–1509
- Low bone mineral density is associated with with bone microdamage accumulation in postmenopausal women with osteoporosis. Bone. 2007;41:378–385
- . Pharmacokinetics/pharmacodynamics of bisphosphonates: use for optimization of intermittent therapy for osteoporosis. Clinical Pharmacokinetics. 2005;44:551–570
- Skeletal retention of bisphosphonate (pamidronate) and its relation to the rate of bone resorption in patients with breast cancer and bone metastases. Journal of Bone and Mineral Research. 2005;20:1543–1547
- Comparison of risedronate and alendronate pharmacokinetics at clinical doses. Osteoporosis International. 2003;14(Suppl. 7):S38
- Treatment with once-weekly alendronate compared to once-weekly risedronate in women with postmenopausal osteoporosis: a randomized, double-blind study. Journal of Bone and Mineral Research. 2005;20:141–151
- . Prolonged bisphosphonate release after treatment in children. The New England Journal of Medicine. 2007;356:1075–1076
- Elimination and biochemical responses to intravenous alendronate in postmenopausal osteoporosis. Journal of Bone and Mineral Research. 1997;12:1700–1707
- A pharmacokinetic and pharmacodynamic model for intravenous bisphosphonate (pamidronate) in osteoporosis. European Journal of Clinical Pharmacology. 2002;57:883–890
- Ten years' experience with alendronate for osteoporosis in postmenopausal women. The New England Journal of Medicine. 2004;350:1189–1199
- Changes in bone density and turnover explain the reductions in incidence of nonvertebral fractures that occur during treatment with antiresorptive agents. The Journal of Clinical Endocrinology and Metabolism. 2002;87:1586–1592
- Change in bone turnover and hip, non-spine, and vertebral fracture in alendronate-treated women: the fracture intervention trial. Journal of Bone and Mineral Research. 2004;19:1250–1258
- . Relationship of early changes in bone resorption to the reduction in fracture risk with risedronate. Journal of Bone and Mineral Research. 2003;18:1051–1056
- The effect of 2-year treatment with the aminobisphosphonate alendronate on bone metabolism, bone histomorphometry and bone strength in overiectomized nonhuman primates. The Journal of Clinical Investigation. 1993;92:2577–2586
- Lifelong administration of high doses of ibandronate increases bone mass and maintains bone quality of lumbar vertebrae in rats. Osteoporosis International. 1998;8:97–103
- Improvement in spine bone density and reduction in risk of vertebral fractures during treatments with antiresorptive drugs. The American Journal of Medicine. 2002;112:281–289
- . Antifracture efficacy of antiresorptive agents are related to changes in bone density. The Journal of Clinical Endocrinology and Metabolism. 2000;85:231–236
- Larger increases in bone mineral density during alendronate therapy are associated with lower risk of new vertebral fractures in women with postmenopausal osteoporosis. Arthritis and Rheumatism. 1999;42:1246–1254
- . A method to assess the proportion of treatment effect explained by a surrogate end point. Statistics in Medicine. 2001;20:3175–3188
- . Relationship between changes in bone mineral density and fracture risk reduction with antiresorptive drags: some issues with meta-analysis. Journal of Bone and Mineral Research. 2004;19:330–337
- . Determinants of bone strength and clinical practice; effects of bisphosphonates. Bone. 2007;41:S3–S7
- Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Fracture Intervention Trial Research Group. Lancet. 1996;348:1535–1541
- Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures: results from the Fracture Intervention Trial. JAMA : The Journal of the American Medical Association. 1998;280:2077–2082
- Effect of oral alendronate on bone mineral density and the incidence of fractures in postmenopausal osteoporosis. The Alendronate Phase III Osteoporosis Treatment Study Group. The New England Journal of Medicine. 1995;333:1437–1443
- Multinational, placebo-controlled, randomized trial of the effects of alendronate on bone density and fracture risk in postmenopausal women with low bone mass: results of the FOSIT study. Fosamax International Trial Study Group. Osteoporosis International. 1999;9:461–468 Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis: a randomized controlled trial. Vertebral Efficacy With Risedronate Therapy (VERT) Study Group. JAMA : The Journal of the American Medical Association. 1999;282:1344–1352
- Effect of risedronate on the risk of hip fracture in elderly women. Hip Intervention Program Study Group. The New England Journal of Medicine. 2001;344:333–340
- Randomized trial of the effects of risedronate on vertebral fractures in women with established postmenopausal osteoporosis. Vertebral Efficacy with Risedronate Therapy (VERT) study group. Osteoporosis International. 2000;11:83–91
- Effects of oral ibandronate administered daily or intermittently on fracture risk in postmenopausal osteoporosis. Journal of Bone and Mineral Research. 2004;19:1241–1249
- Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. The New England Journal of Medicine. 2007;356:1809–1822
- Zoledronic acid in reducing clinical fracture and mortality after hip fracture. The New England Journal of Medicine. 2007;357:nihpa40967
- Daily oral pamidronate in women and men with osteoporosis: a 3-year randomized placebo-controlled clinical trial with a 2-year open extension. Journal of Bone and Mineral Research. 2002;17:1057–1064
- Clodronate reduces vertebral fracture risk in women with postmenopausal or secondary osteoporosis: results of a double-blind, placebo-controlled 3-year study. Journal of Bone and Mineral Research. 2004;19:728–736
- Clodronate reduces the incidence of fractures in community-dwelling elderly women unselected for osteoporosis: results of a double-blind, placebo-controlled randomized study. Journal of Bone and Mineral Research. 2007;22:135–141
- Prevention of nonvertebral fractures by alendronate. A meta-analysis. Alendronate Osteoporosis Treatment Study Groups. JAMA : The Journal of the American Medical Association. 1997;277:1159–1164
- Meta-analyses of therapies for postmenopausal osteoporosis. II. Meta-analysis of alendronate for the treatment of postmenopausal women. Endocrine Reviews. 2002;23:508–516
- Meta-analyses of therapies for postmenopausal osteoporosis. III. Meta-analysis of risedronate for the treatment of postmenopausal osteoporosis. Endocrine Reviews. 2002;23:517–523
- Meta-analysis of the efficacy of alendronate for the prevention of hip fractures in postmenopausal women. Osteoporosis International. 2005;16:468–474
- Vertebral fracture risk reduction with risedronate in post-menopausal women with osteoporosis: a meta-analysis of individual patient data. Aging Clinical and Experimental Research. 2005;17:150–156
- Effect of osteoporosis treatments on risk of non-vertebral fractures: review and meta-analysis of intention-to-treat studies. Osteoporosis International. 2005;16:1291–1298
- Alendronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women. Cochrane Database of Systematic Reviews. 2008;(1):CD001155
- Risedronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women. Cochrane Database of Systematic Reviews. 2008;(1):CD004523
- . Anti-hip fracture efficacy of biophosphonates: a Bayesian analysis of clinical trials. Journal of Bone and Mineral Research. 2006;21:340–349
- Ibandronate for the prevention of non-vertebral fractures: A pooled analysis of individual patient data. Osteoporosis International,. 29 July 2008;[Epub ahead of print]
- . A single IV injection of equipotent doses of alendronate, risedronate, ibandronate and zoledronic acid exerts a bone protective effect of similar magnitude and duration in ovariectomized rats. Journal of Bone and Mineral Research. 2004;19(Suppl. 1):S307
- . Changes in bone remodelling and antifracture efficacy of intermittent bisphosphonate therapy: implications from clinical studies with ibandronate. Annals of the Rheumatic Diseases. 2007;66:853–858
- Early Postmenopausal Intervention Cohort Study. Prevention of postmenopausal bone loss: six-year results from the Early Postmenopausal Intervention Cohort Study. The Journal of Clinical Endocrinology and Metabolism. 2004;89:4879–4885
- Changes in bone mineral density and turnover after alendronate or estrogen withdrawal. Menopause. 2004;11:622–630
- Alendronate has a residual effect on bone mass in post-menopausal Danish women up to 7 years after treatment withdrawal. Bone. 2003;33:301–307
- Skeletal metabolism in patients with osteoporosis after discontinuation of long-term treatment with oral pamidronate. The Journal of Clinical Endocrinology and Metabolism. 1995;80:3465–3468
- Effects of continuing or stopping alendronate after 5 years of treatment: the Fracture Intervention Trial Long-term Extension (FLEX): a randomized trial. JAMA : The Journal of the American Medical Association. 2006;296:2927–2938
- Fracture risk remains reduced one year after discontinuation of risedronate. Osteoporosis International. 2008;19:365–372
- Effect of 1 year of discontinuation of raloxifene or estrogen therapy on bone mineral density after 5 years of treatment in healthy postmenopausal women. Bone. 2002;30:599–603
- Efficacy of continued alendronate for fractures in women without vertebral fracture. Journal of Bone and Mineral Research. 2007;22(Suppl. 1):S16–S17
- Seven years of treatment with risedronate in women with postmenopausal osteoporosis. Calcified Tissue International. 2004;75:462–468
- Severely suppressed bone turnover: a potential complication of alendronate therapy. The Journal of Clinical Endocrinology and Metabolism. 2005;90:1294–1301
- Subtrochanteric insufficiency fractures in patients on alendronate therapy: a caution. The Journal of Bone and Joint Surgery. British Volume. 2007;89:349–353
- An emerging pattern of subtrochanteric stress fractures: a long-term complication of alendronate therapy?. Injury. 2008;39:224–231
- . Atypical fractures of the femoral diaphysis in postmenopausal women taking alendronate. The New England Journal of Medicine. 2008;358:1304–1305
- Effects of prior antiresorptive therapy on markers of bone formation after 6 months of teriparatide treatment in postmenopausal women with osteoporosis: results from the Eurofors trial. Calcified Tissue International. 2007;80(Suppl. 1):s137
- Bone turnover markers demonstrate greater earlier responsiveness to teriparatide following treatment with risedronate compared with alendronate: the OPTAMISE study. Journal of Bone and Mineral Research. 2007;22(Suppl. 1):S27
- Intravenous zoledronic acid 5 mg in the treatment of postmenopausal women with low bone density previously treated with alendronate. Bone. 2007;41:122–128
- Bisphosphonate-associated osteonecrosis of the jaw: report of a task force of the American Society for Bone and Mineral Research. Journal of Bone and Mineral Research. 2007;22:1479–1491
- Osteonecrosis of the jaw and bisphosphonate treatment for osteoporosis. Bone. 2008;42:841–847
PII: S1521-690X(08)00079-1
doi: 10.1016/j.beem.2008.07.001
© 2008 Elsevier Ltd. All rights reserved.
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Best Practice & Research Clinical Endocrinology & Metabolism
Volume 22, Issue 5
, Pages 831-847
, October 2008
