Bisphosphonate therapeutics in bone disease: The hard and soft data on osteoclast inhibition

Molecular Interventions

Volumn 10, Issue 3, 2010, Pages 141-152

  Drake, Matthew T ^a   Cremers, Serge C L M ^b  

^a MAYO CLINIC   (United States)

^b Och Spine at New York Presbyterian Hospitals   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALENDRONIC ACID; ANTIBIOTIC AGENT; BISPHOSPHONIC ACID DERIVATIVE; CALCIUM; CLODRONIC ACID; ETIDRONIC ACID; HYDROXYAPATITE; IBANDRONIC ACID; PAMIDRONIC ACID; RISEDRONIC ACID; TILUDRONIC ACID; VITAMIN D; ZOLEDRONIC ACID;

ABDOMINAL PAIN; ACUTE KIDNEY TUBULE NECROSIS; ARTHRALGIA; BONE DENSITY; BONE DETERIORATION; BONE DEVELOPMENT; BONE DISEASE; BONE METASTASIS; BONE REMODELING; BONE TURNOVER; BREAST CANCER; CALCIUM BLOOD LEVEL; CANCER SURGERY; CLINICAL TRIAL; COMPETITIVE INHIBITION; CONJUNCTIVITIS; CORTICOSTEROID INDUCED OSTEOPOROSIS; COST EFFECTIVENESS ANALYSIS; DENTAL SURGERY; DETERIORATION; DRUG BIOAVAILABILITY; DRUG CYTOTOXICITY; DRUG FEVER; DRUG HALF LIFE; DRUG INDUCED HEADACHE; DRUG MARKETING; DRUG MEGADOSE; DRUG STRUCTURE; DRUG UPTAKE; DRUG WITHDRAWAL; DYSPEPSIA; EPISCLERITIS; ESOPHAGUS CANCER; EYE PAIN; FEMUR SUBTROCHANTERIC FRACTURE; FLU LIKE SYNDROME; FRAGILITY FRACTURE; GASTRITIS; GLOMERULONEPHRITIS; HEART ATRIUM FIBRILLATION; HIGH RISK PATIENT; HIP FRACTURE; HUMAN; HYPERCALCEMIA; HYPOCALCEMIA; INCIDENCE; JAW OSTEONECROSIS; MALAISE; MULTIPLE MYELOMA; MUSCULOSKELETAL PAIN; MYALGIA; NAUSEA; NONHUMAN; OSSIFICATION; OSTEOBLAST; OSTEOCLAST; OSTEOGENESIS IMPERFECTA; OSTEOLYSIS; OSTEOMALACIA; OSTEOPOROSIS; PAGET BONE DISEASE; PARATHYROID HORMONE BLOOD LEVEL; PATIENT COMPLIANCE; PHOTOPHOBIA; POSTMENOPAUSE OSTEOPOROSIS; PRESCRIPTION; PROSTATE CANCER; REVIEW; RISK REDUCTION; SCLERITIS; SIDE EFFECT; SINGLE DRUG DOSE; UVEITIS; VERTEBRA FRACTURE;

BONE DENSITY CONSERVATION AGENTS; BONE DISEASES; DIPHOSPHONATES; GERANYLTRANSTRANSFERASE; HUMANS; MODELS, BIOLOGICAL; OSTEOCLASTS;

EID: 77953517352     PISSN: 15340384     EISSN: 15432548     Source Type: Journal    
DOI: 10.1124/mi.10.3.5     Document Type: Review

References (99)

1. Blomen LJMJ Discovery and history of the non-medical uses of bisphosphonates., in Bisphosphonates on Bone, Bijvoet OLM, Fleisch HA, Canfield RE, Russell RGG, editors. 1995, Elsevier Sciences: Amsterdam. pp. 111-124.
2. Fleisch H, Russell RG, and Francis MD (1969) Diphosphonates inhibit hydroxyapatite dissolution in vitro and bone resorption in tissue culture and in vivo. Science 165:1262-1264.
3. Fleisch H, Russell RG, and Straumann F (1966) Effect of pyrophosphate on hydroxyapatite and its implications in calcium homeostasis. Nature 212:901-903.
4. Russell RG, Mühlbauer RC, Bisaz S, Williams DA, and Fleisch H (1970) The influence of pyrophosphate, condensed phosphates, phosphonates and other phosphate compounds on the dissolution of hydroxyapatite in vitro and on bone resorption induced by parathyroid hormone in tissue culture and in thyroparathyroidectomised rats. Calcif Tissue Res 6:183-196.
5. Ebetino FH and Dansereau, SM Bisphosphonate antiresorptive structure-activity relationships, in Bisphosphonates on Bone, Bijvoet OLM, Fleisch HA, Canfield RE, Russell RGG, editors. 1995, Elsevier Sciences: Amsterdam. pp. 139-153.
6. Russell RG, Watts NB, Ebetino FH, and Rogers MJ (2008) Mechanisms of action of bisphosphonates: Similarities and differences and their potential influence on clinical efficacy. Osteoporos Int. 19:733-759.
7. Russell RG (2006) Bisphosphonates: From bench to bedside. Ann NY Acad Sci 1068:367-401.
8. Dunford JE, Thompson K, Coxon FP, Luckman SP, Hahn FM, Poulter CD, Ebetino FH, and Rogers MJ (2001) Structure-activity relationships for inhibition of farnesyl diphosphate synthase in vitro and inhibition of bone resorption in vivo by nitrogen-containing bisphosphonates. J Pharmacol Exp Ther 296:235-242. (Pubitemid 32112446)
9. Thompson K, Rogers MJ, Coxon FP, and Crockett JC (2006) Cytosolic entry of bisphosphonate drugs requires acidification of vesicles after fluid-phase endocytosis. Mol Pharmacol 69:1624-1632.
10. Roelofs AJ, Coxon FP, Ebetino FH, Lundy MW, Henneman ZJ, Nancollas GH, Sun S, Blazewska KM, Bala JLF, Kashemirov BA, et al. (2009) Fluorescent risedronate analogs reveal bisphosphonate uptake by bone marrow monocytes and localization around osteocytes in vivo. J Bone Miner Res Oct 12. [Epub ahead of print]
11. Plotkin LI, Weinstein RS, Parfitt AM, Roberson PK, Manolagas SC, and Bellido T (1999) Prevention of osteocyte and osteoblast apoptosis by bisphosphonates and calcitonin. J Clin Invest 104:1363-1374.
12. Follet H, Li J, Phipps RJ, Hui S, Condon K, and Burr DB (2007) Risedronate and alendronate suppress osteocyte apoptosis following cyclic fatigue loading. Bone 40:1172-1177.
13. Plotkin LI, Manolagas SC, and Bellido T (2006) Dissociation of the pro-apoptotic effects of bisphosphonates on osteoclasts from their anti-apoptotic effects on osteoblasts/osteocytes with novel analogs. Bone 39:443-52.
14. Frith JC, Mönkkönen J, Blackburn GM, Russell RG, and Rogers MJ (1997) Clodronate and liposome-encapsulated clodronate are metabolized to a toxic ATP analog, adenosine 5′-(beta, gamma-dichloromethylene) triphosphate, by mammalian cells in vitro. J Bone Miner Res 12:1358-1367.
15. Kavanagh KL, Guo K, Dunford JE, Wu X, Knapp S, Ebetino FH, Rogers MJ, Russell RG, and Oppermann U (2006) The molecular mechanism of nitrogen-containing bisphosphonates as antiosteoporosis drugs. Proc Natl Acad Sci USA 103:7829-7834.
16. Luckman SP, Hughes DE, Coxon FP, Graham R, Russell G, and Rogers MJ (1998) Nitrogen-containing bisphosphonates inhibit the mevalonate pathway and prevent post-translational prenylation of GTP-binding proteins, including Ras. J Bone Miner Res 13:581-589.
17. van Beek ER, Cohen LH, Leroy IM, Ebetino FH, Löwik CW, and Papapoulos SE (2003) Differentiating the mechanisms of antiresorptive action of nitrogen containing bisphosphonates. Bone 33:805-811.
18. Mao J, Mukherjee S, Zhang Y, Cao R, Sanders JM, Song Y, Zhang Y, Meints GA, Gao YG, Mukkamala D, et al. (2006) Solid-state NMR, crystallographic, and computational investigation of bisphosphonates and farnesyl diphosphate synthase-bisphosphonate complexes. J Am Chem Soc 128:14485-14497.
19. Hall A (1998) Rho GTPases and the actin cytoskeleton. Science 279:509-514.
20. Weinstein RS, Roberson PK, and Manolagas SC, (2009) Giant osteoclast formation and long-term oral bisphosphonate therapy. N Engl J Med 360:53-62.
21. Cremers SC, Pillai G, and Papapoulos SE (2005) Pharmacokinetics/ pharmacodynamics of bisphosphonates: Use for optimisation of intermittent therapy for osteoporosis. Clin Pharmacokinet 44:551-570.
22. Cremers S and Garnero P (2006) Biochemical markers of bone turnover in the clinical development of drugs for osteoporosis and metastatic bone disease: Potential uses and pitfalls. Drugs 66:2031-2058.
23. Rizzoli R, Greenspan SL, Bone G 3rd, Schnitzer TJ, Watts NB, Adami S, Foldes AJ, Roux C, Levine MA, Uebelhart B, et al. (2002) Two-year results of once-weekly administration of alendronate 70 mg for the treatment of postmenopausal osteoporosis. J Bone Miner Res 17:1988-1996.
24. Brown JP, Kendler DL, McClung MR, Emkey RD, Adachi JD, Bolognese MA, Li Z, Balske A, and Lindsay R (2002) The efficacy and tolerability of risedronate once a week for the treatment of postmenopausal osteoporosis. Calcif Tissue Int 71:103-111.
25. Reid IR, Brown JP, Burckhardt P, Horowitz Z, Richardson P, Trechsel U, Widmer A, Devogelaer JP, Kaufman JM, Jaeger P, et al. (2002) Intravenous zoledronic acid in postmenopausal women with low bone mineral density. N Engl J Med 346:653-661. (Pubitemid 34815869)
26. Black DM, Delmas PD, Eastell R, Reid IR, Boonen S, Cauley JA, Cosman F, Lakatos P, Leung PC, Man Z, et al. (2007) Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med 356:1809-1822.
27. Sato M, Grasser W, Endo N, Akins R, Simmons H, Thompson DD, Golub E, and Rodan GA (1991) Bisphosphonate action. Alendronate localization in rat bone and effects on osteoclast ultrastructure. J Clin Invest 88:2095-2105.
28. Khan SA, Kanis JA, Vasikaran S, Kline WF, Matuszewski BK, McCloskey EV, Beneton MN, Gertz BJ, Sciberras DG, Holland SD, et al. (1997) Elimination and biochemical responses to intravenous alendronate in postmenopausal osteoporosis. J Bone Miner Res 12:1700-1707.
29. Lin JH (1996) Bisphosphonates: A review of their pharmacokinetic properties. Bone 18:75-85.
30. Yood RA, Emani S, Reed JI, Lewis BE, Charpentier M, and Lydick E (2003) Compliance with pharmacologic therapy for osteoporosis. Osteoporos Int 14:965-968.
31. Siris ES, Harris ST, Rosen CJ, Barr CE, Arvesen JN, Abbott TA, and Silverman S (2006) Adherence to bisphosphonate therapy and fracture rates in osteoporotic women: Relationship to vertebral and nonvertebral fractures from 2 US claims databases. Mayo Clin Proc 81:1013-1022.
32. Black DM, Cummings SR, Karpf DB, Cauley JA, Thompson DE, Nevitt MC, Bauer DC, Genant HK, Haskell WL, Marcus R, et al. (1996) Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Fracture Intervention Trial Research Group. Lancet 348:1535-1541.
33. Cummings SR, Black DM, Thompson DE, Applegate WB, Barrett-Connor E, Musliner TA, Palermo L, Prineas R, Rubin SM, Scott JC, et al. (1998) Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures: Results from the Fracture Intervention Trial. JAMA 280:2077-2082.
34. Harris ST, Watts NB, Genant HK, McKeever CD, Hangartner T, Keller M, Chesnut CH 3rd, Brown J, Eriksen EF, Hoseyni MS, et al. (1999) 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 282:1344-1352.
35. McClung MR, Geusens P, Miller PD, Zippel H, Bensen WG, Roux C, Adami S, Fogelman I, Diamond T, Eastell R, et al. (2001) Effect of risedronate on the risk of hip fracture in elderly women. Hip Intervention Program Study Group. N Engl J Med 344:333-340.
36. Delmas PD, Recker RR, Chesnut CH 3rd, Skag A, Stakkestad JA, Emkey R, Gilbride J, Schimmer RC, and Christiansen C (2004) Daily and intermittent oral ibandronate normalize bone turnover and provide significant reduction in vertebral fracture risk: Results from the BONE study. Osteoporos Int 15:792-798.
37. Chesnut CH 3rd, Skag A, Christiansen C, Recker R, Stakkestad JA, Hoiseth A, Felsenberg D, Huss H, Gilbride J, Schimmer RC, et al. (2004) Effects of oral ibandronate administered daily or intermittently on fracture risk in postmenopausal osteoporosis. J Bone Miner Res 19:1241-1249.
38. Orwoll E, Ettinger M, Weiss S, Miller P, Kendler D, Graham J, Adami S, Weber K, Lorenc R, Pietschmann P, et al., (2000) Alendronate for the treatment of osteoporosis in men. N Engl J Med 343:604-610.
39. Finkelstein JS, Leder BZ, Burnett SM, Wyland JJ, Lee H, de la Paz AV, Gibson K, and Neer RM (2006) Effects of teriparatide, alendronate, or both on bone turnover in osteoporotic men. J Clin Endocrinol Metab 91:2882-2887.
40. Kurland ES, Heller SL, Diamond B, McMahon DJ, Cosman F, and Bilezikian JP (2004) The importance of bisphosphonate therapy in maintaining bone mass in men after therapy with teriparatide [human parathyroid hormone(1-34)]. Osteoporos Int 15:992-997.
41. Curtis JR, Westfall AO, Allison J, Becker A, Melton ME, Freeman A, Kiefe CI, MacArthur M, Ockershausen T, Stewart E, et al. (2007) Challenges in improving the quality of osteoporosis care for long-term glucocorticoid users: A prospective randomized trial. Arch Intern Med 167:591-596.
42. de Nijs RN, Jacobs JW, Lems WF, Laan RF, Algra A, Huisman AM, Buskens E, de Laet CE, Oostveen AC, Geusens PP, et al. (2006) Alendronate or alfacalcidol in glucocorticoid-induced osteoporosis. N Engl J Med 355:675-864.
43. van Staa TP, Geusens P, Zhang B, Leufkens HG, Boonen A, and Cooper C (2007) Individual fracture risk and the cost-effectiveness of bisphosphonates in patients using oral glucocorticoids. Rheumatology (Oxford) 46:460-466.
44. Coco M, Glicklich D, Faugere MC, Burris L, Bognar I, Durkin P, Tellis V, Greenstein S, Schechner R, Figueroa K, et al. (2003) Prevention of bone loss in renal transplant recipients: A prospective, randomized trial of intravenous pamidronate. J Am Soc Nephrol 14:2669-2676.
45. Aris RM, Lester GE, Renner JB, Winders A, Denene Blackwood A, Lark RK, and Ontjes DA (2000) Efficacy of pamidronate for osteoporosis in patients with cystic fibrosis following lung transplantation. Am J Respir Crit Care Med 162(3 Pt 1):941-946.
46. Grotz W, Nagel C, Poeschel D, Cybulla M, Petersen KG, Uhl M, Strey C, Kirste G, Olschewski M, Reichelt A, et al. (2001) Effect of ibandronate on bone loss and renal function after kidney transplantation. J Am Soc Nephrol 12:1530-1537. (Pubitemid 32666337)
47. Giannini S, D'Angelo A, Carraro G, Nobile M, Rigotti P, Bonfante L, Marchini F, Zaninotto M, Dalle Carbonare L, Sartori L, et al. (2001) Alendronate prevents further bone loss in renal transplant recipients. J Bone Miner Res 16:2111-2117. (Pubitemid 32995403)
48. Krieg MA, Seydoux C, Sandini L, Goy JJ, Berguer DG, Thiébaud D, and Burckhardt P (2001) Intravenous pamidronate as treatment for osteoporosis after heart transplantation: A prospective study. Osteoporos Int 12:112-116.
49. Grigg AP, Shuttleworth P, Reynolds J, Schwarer AP, Szer J, Bradstock K, Hui C, Herrmann R, and Ebeling PR (2006) Pamidronate reduces bone loss after allogeneic stem cell transplantation. J Clin Endocrinol Metab 91:3835-3843. (Pubitemid 44536852)
50. D'Souza AB, Grigg AP, Szer J, and Ebeling PR (2006) Zoledronic acid prevents bone loss after allogeneic haemopoietic stem cell transplantation. Intern Med J 36:600-603. (Pubitemid 44179835)
51. Yao S, McCarthy PL, Dunford LM, Roy DM, Brown K, Paplham P, Syta M, Lamonica D, Smiley S, Battiwalla M, et al. (2008) High prevalence of early-onset osteopenia/osteoporosis after allogeneic stem cell transplantation and improvement after bisphosphonate therapy. Bone Marrow Transplant 41:393-398.
52. Whyte MP (2006) Clinical practice. Paget's disease of bone. N Engl J Med 355:593-600.
53. Reid IR, Miller P, Lyles K, Fraser W, Brown JP, Saidi Y, Mesenbrink P, Su G, Pak J, Zelenakas K, et al., (2005) Comparison of a single infusion of zoledronic acid with risedronate for Paget's disease. N Engl J Med 353:898-908.
54. Body JJ Treatment and prevention of bone metastases and myeloma in bone disease, in Primer on the metabolic diseases and disorders of mineral metabolism, M.J. Favus, Editor. 2006, American Society for Bone and Mineral Research: Washington, D.C. p. 383-390.
55. Hortobagyi GN, Theriault RL, Lipton A, Porter L, Blayney D, Sinoff C, Wheeler H, Simeone JF, Seaman JJ, Knight RD, et al. (1998) Long-term prevention of skeletal complications of metastatic breast cancer with pamidronate. Protocol 19 Aredia Breast Cancer Study Group. J Clin Oncol 16:2038-2044.
56. Lipton A, Theriault RL, Hortobagyi GN, Simeone J, Knight RD, Mellars K, Reitsma DJ, Heffernan M, and Seaman JJ (2000) Pamidronate prevents skeletal complications and is effective palliative treatment in women with breast carcinoma and osteolytic bone metastases: Long term follow-up of two randomized, placebo-controlled trials. Cancer 88:1082-1090. (Pubitemid 30127670)
57. Rosen LS, Gordon D, Tchekmedyian NS, Yanagihara R, Hirsh V, Krzakowski M, Pawlicki M, De Souza P, Zheng M, Urbanowitz G, et al. (2004) Long-term efficacy and safety of zoledronic acid in the treatment of skeletal metastases in patients with nonsmall cell lung carcinoma and other solid tumors: a randomized, Phase III, double-blind, placebo-controlled trial. Cancer 100:2613-2621. (Pubitemid 38715767)
58. Clemons MJ, Dranitsaris G, Ooi WS, Yogendran G, Sukovic T, Wong BY, Verma S, Pritchard KI, Trudeau M, and Cole DE (2006) Phase II trial evaluating the palliative benefit of second-line zoledronic acid in breast cancer patients with either a skeletal-related event or progressive bone metastases despite first-line bisphosphonate therapy. J Clin Oncol 24:4895-4900. (Pubitemid 46630917)
59. Body JJ, Diel IJ, Lichinitser MR, Kreuser ED, Dornoff W, Gorbunova VA, Budde M, and Bergström B; MF 4265 Study Group. (2003) Intravenous ibandronate reduces the incidence of skeletal complications in patients with breast cancer and bone metastases. Ann Oncol 14:1399-1405.
60. Gnant MF, Mlineritsch B, Luschin-Ebengreuth G, Grampp S, Kaessmann H, Schmid M, Menzel C, Piswanger-Soelkner JC, Galid A, Mittlboeck M, et al. (2007) Zoledronic acid prevents cancer treatment-induced bone loss in premenopausal women receiving adjuvant endocrine therapy for hormone-responsive breast cancer: a report from the Austrian Breast and Colorectal Cancer Study Group. J Clin Oncol 25:820-828.
61. Confavreux CB, Fontana A, Guastalla JP, Munoz F, Brun J, and Delmas PD (2007) Estrogen-dependent increase in bone turnover and bone loss in postmenopausal women with breast cancer treated with anastrozole. Prevention with bisphosphonates. Bone 41:346-352.
62. Gnant M, Mlineritsch B, Schippinger W, Luschin-Ebengreuth G, Pöstlberger S, Menzel C, Jakesz R, Seifert M, Hubalek M, Bjelic-Radisic V, et al. (2009) Endocrine therapy plus zoledronic acid in premenopausal breast cancer. N Engl J Med 360:679-691.
63. McCloskey, E., Paterson A, Kanis J, Tähtelä R, and Powles T (2010) Effect of oral clodronate on bone mass, bone turnover and subsequent metastases in women with primary breast cancer. Eur J Cancer 46:558-565.
64. Garnero P, Buchs N, Zekri J, Rizzoli R, Coleman RE, and Delmas PD (2000) Markers of bone turnover for the management of patients with bone metastases from prostate cancer. Br J Cancer 82:858-864.
65. Saad F, Gleason DM, Murray R, Tchekmedyian S, Venner P, Lacombe L, Chin JL, Vinholes JJ, Goas JA, Chen B, et al., (2002) A randomized, placebo-controlled trial of zoledronic acid in patients with hormonerefractory metastatic prostate carcinoma. J Natl Cancer Inst 94:1458-1468.
66. Saad F, Gleason DM, Murray R, Tchekmedyian S, Venner P, Lacombe L, Chin JL, Vinholes JJ, Goas JA, Zheng M, et al. (2004) Long-term efficacy of zoledronic acid for the prevention of skeletal complications in patients with metastatic hormone-refractory prostate cancer. J Natl Cancer Inst 96:879-882. (Pubitemid 38807610)
67. Saad F, Abrahamsson PA, and Miller K (2009) Preserving bone health in patients with hormone-sensitive prostate cancer: The role of bisphosphonates. BJU Int 104:1573-1579.
68. Berenson JR, Lichtenstein A, Porter L, Dimopoulos MA, Bordoni R, George S, Lipton A, Keller A, Ballester O, Kovacs MJ, et al. (1996) Efficacy of pamidronate in reducing skeletal events in patients with advanced multiple myeloma. Myeloma Aredia Study Group. N Engl J Med 334:488-493. (Pubitemid 26067736)
69. Berenson JR, Rosen LS, Howell A, Porter L, Coleman RE, Morley W, Dreicer R, Kuross SA, Lipton A, and Seaman JJ (2001) Zoledronic acid reduces skeletal-related events in patients with osteolytic metastases. Cancer 91:1191-1200.
70. Rosen LS, Gordon D, Kaminski M, Howell A, Belch A, Mackey J, Apffelstaedt J, Hussein M, Coleman RE, Reitsma DJ, et al. (2001) Zoledronic acid versus pamidronate in the treatment of skeletal metastases in patients with breast cancer or osteolytic lesions of multiple myeloma: A phase III, double-blind, comparative trial. Cancer J 7:377-387. (Pubitemid 33759002)
71. Lipton A, Zheng M, and Seaman J (2003) Zoledronic acid delays the onset of skeletal-related events and progression of skeletal disease in patients with advanced renal cell carcinoma. Cancer 98:962-969.
72. Castillo H and Samson-Fang L (2009) Effects of bisphosphonates in children with osteogenesis imperfecta: an AACPDM systematic review. Dev Med Child Neurol 51:17-29.
73. Zeitlin L, Fassier F, and Glorieux FH (2003) Modern approach to children with osteogenesis imperfecta. J Pediatr Orthop B 12:77-87.
74. Kennel KA and Drake MT (2009) Adverse effects of bisphosphonates: implications for osteoporosis management. Mayo Clin Proc 84:632-637; quiz 638.
75. Wysowski DK (2009) Reports of esophageal cancer with oral bisphosphonate use. N Engl J Med 360:89-90.
76. U.S. Food and Drug Administration. FDA Alert: Information for Healthcare Professionals: Bisphosphonates (marketed as Actonel, Actonel+Ca, Aredia, Boniva, Didronel, Fosamax, Fosamax+D, Reclast, Skelid, and Zometa). 2008 March 11, 2010 [cited; Available from: http://www.fda.gov/Drugs/DrugSafety/ PostmarketDrugSafetyInformationforPatientsandProviders/ucm124165.htm.
77. Dicuonzo G, Vincenzi B, Santini D, Avvisati G, Rocci L, Battistoni F, Gavasci M, Borzomati D, Coppola R, and Tonini G (2003) Fever after zoledronic acid administration is due to increase in TNF-alpha and IL-6. J Interferon Cytokine Res 23:649-654.
78. Thompson K and Rogers MJ (2004) Statins prevent bisphosphonate-induced gamma,delta-T-cell proliferation and activation in vitro. J Bone Miner Res 19:278-288.
79. Khosla S, Burr D, Cauley J, Dempster DW, Ebeling PR, Felsenberg D, Gagel RF, Gilsanz V, Guise T, Koka S, et al. (2007) Bisphosphonate-associated osteonecrosis of the jaw: Report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res 22:1479-1491.
80. Woo SB, Hellstein JW, and Kalmar JR (2006) Narrative [corrected] review: Bisphosphonates and osteonecrosis of the jaws. Ann Intern Med 144:753-761. (Pubitemid 46780635)
81. Montefusco V, Gay F, Spina F, Miceli R, Maniezzo M, Teresa Ambrosini M, Farina L, Piva S, Palumbo A, Boccadoro M, et al., (2008) Antibiotic prophylaxis before dental procedures may reduce the incidence of osteonecrosis of the jaw in patients with multiple myeloma treated with bisphosphonates. Leuk Lymphoma 49:2156-2162.
82. Cummings SR, Schwartz AV, and Black DM (2007) Alendronate and atrial fibrillation. N Engl J Med 356:1895-1896.
83. Sørensen HT, Christensen S, Mehnert F, Pedersen L, Chapurlat RD, Cummings SR, and Baron JA. (2008) Use of bisphosphonates among women and risk of atrial fibrillation and flutter: Population based case-control study. BMJ 336:813-81.
84. Karam R, Camm J, and McClung M (2007) Yearly zoledronic acid in postmenopausal osteoporosis. N Engl J Med 357:712-713.
85. Bhuriya, R., Singh M, Molnar J, Arora R, Khosla S (2010) Bisphosphonate use in women and the risk of atrial fibrillation: A systematic review and meta-analysis. Int J Cardiol. Jan 3. [Epub ahead of print]
86. Odvina CV, Zerwekh JE, Rao DS, Maalouf N, Gottschalk FA, and Pak CY (2005) Severely suppressed bone turnover: A potential complication of alendronate therapy. J Clin Endocrinol Metab 90:1294-1301.
87. Armamento-Villareal R, Napoli N, Panwar V, and Novack D (2006) Suppressed bone turnover during alendronate therapy for high-turnover osteoporosis. N Engl J Med 355:2048-2050.
88. Bone HG, Hosking D, Devogelaer JP, Tucci JR, Emkey RD, Tonino RP, Rodriguez-Portales JA, Downs RW, Gupta J, Santora AC, et al. (2004) Ten years' experience with alendronate for osteoporosis in postmenopausal women. N Engl J Med 350:1189-1199.
89. Black DM, Schwartz AV, Ensrud KE, Cauley JA, Levis S, Quandt SA, Satterfield S, Wallace RB, Bauer DC, Palermo L, et al. (2006) Effects of continuing or stopping alendronate after 5 years of treatment: The Fracture Intervention Trial Long-term Extension (FLEX): A randomized trial. JAMA 296:2927-2938.
90. Abrahamsen B, Eiken P, and Eastell R (2009) Subtrochanteric and diaphyseal femur fractures in patients treated with alendronate: A register-based national cohort study. J Bone Miner Res 24:1095-1102.
91. Schneider JP (2009) Bisphosphonates and low-impact femoral fractures: current evidence on alendronate-fracture risk. Geriatrics 64:18-23.
92. Lenart BA, Neviaser AS, Lyman S, Chang CC, Edobor-Osula F, Steele B, van der Meulen MC, Lorich DG, and Lane JM (2009) Association of low-energy femoral fractures with prolonged bisphosphonate use: A case control study. Osteoporos Int 20:1353-1362.
93. Lenart BA, Lorich DG, and Lane JM (2008) Atypical fractures of the femoral diaphysis in postmenopausal women taking alendronate. N Engl J Med 358:1304-1306.
94. Kwek EB, Koh JS, and Howe TS (2008) More on atypical fractures of the femoral diaphysis. N Engl J Med 359:316-317.
95. FDA Drug Safety Communication: Ongoing safety review of oral bisphosphonates and atypical subtrochanteric femur fractures. 2010 March 11, 2010 [cited; Available from: http://www.fda.gov/Drugs/DrugSafety/ PostmarketDrugSafetyInformationforPatientsandProviders/ucm203891.htm.
96. Black DM, Kelly MP, Genant HK, Palermo L, Eastell R, Bucci- Rechtweg C, Cauley J, Leung PC, Boonen S, Santora A et al. (2010) Bisphosphonates and fractures of the subtrochanteric or diaphyseal femur. N Engl J Med 362:1825-1827.
97. Smetana, S., Michlin A, Rosenman E, Biro A, Boaz M, and Katzir Z. (2004) Pamidronate-induced nephrotoxic tubular necrosis - A case report. Clin Nephrol 61:63-67. (Pubitemid 38100846)
98. Chang JT, Green L, and Beitz J (2003) Renal failure with the use of zoledronic acid. N Engl J Med 349:1676-1679.
99. Body JJ (2006) The risk of cumulative renal effects of intravenous bisphosphonates. Support Cancer Ther 3:77-83.