Bisphosphonates and nonhealing femoral fractures: Analysis of the FDA adverse event reporting system (FAERS) and international safety efforts: A systematic review from the research on adverse drug events and reports (RADAR) project

Journal of Bone and Joint Surgery

Volumn 95, Issue 4, 2013, Pages 297-307

  Edwards, Beatrice J ^a   Bunta, Andrew D ^a   Lane, Joseph ^b   Odvina, Clarita ^c   Rao, D Sudhaker ^d   Raisch, Dennis W ^e   McKoy, June M ^a   Omar, Imran ^a   Belknap, Steven M ^a   Garg, Vishvas ^e   Hahr, Allison J ^a   Samaras, Athena T ^a   Fisher, Matthew J ^a   West, Dennis P ^a   Langman, Craig B ^f   Stern, Paula H ^a  

^a NORTHWESTERN UNIVERSITY   (United States)

^b WEILL CORNELL MEDICAL COLLEGE   (United States)

^c UNIVERSITY OF TEXAS AT DALLAS   (United States)

^d HENRY FORD HOSPITAL   (United States)

^e UNIVERSITY OF NEW MEXICO   (United States)

^f CHILDREN'S MEMORIAL HOSPITAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALENDRONIC ACID; BISPHOSPHONIC ACID DERIVATIVE; IBANDRONIC ACID; PAMIDRONIC ACID; RISEDRONIC ACID; ZOLEDRONIC ACID; BONE DENSITY CONSERVATION AGENT;

BAYES THEOREM; CASE CONTROL STUDY; DATA BASE; DRUG SAFETY; FEMUR FRACTURE; FOOD AND DRUG ADMINISTRATION; FRACTURE NONUNION; HUMAN; NONHEALING FEMORAL FRACTURE; PRIORITY JOURNAL; REVIEW; SYSTEMATIC REVIEW; CHEMICALLY INDUCED DISORDER; DRUG SURVEILLANCE PROGRAM; FRACTURE HEALING; RISK FACTOR; UNITED STATES;

ADVERSE DRUG REACTION REPORTING SYSTEMS; BAYES THEOREM; BONE DENSITY CONSERVATION AGENTS; DIPHOSPHONATES; FEMORAL FRACTURES; FRACTURE HEALING; HUMANS; RISK FACTORS; UNITED STATES; UNITED STATES FOOD AND DRUG ADMINISTRATION;

MLCS; MLOWN;

EID: 84877929848     PISSN: 00219355     EISSN: 15351386     Source Type: Journal    
DOI: 10.2106/JBJS.K.01181     Document Type: Review

References (118)

1. Browner WS, Pressman AR, Nevitt MC, Cummings SR. Mortality following fractures in older women. The study of osteoporotic fractures. Arch Intern Med. 1996 Jul 22;156 (14):1521-5.
2. Johnell O, Kanis JA, Odén A, Sernbo I, Redlund-Johnell I, Petterson C, De Laet C, Jönsson B. Mortality after osteoporotic fractures. Osteoporos Int. 2004 Jan;15 (1): 38-42. Epub 2003 Oct 30.
3. Cauley JA, Thompson DE, Ensrud KC, Scott JC, Black D. Risk ofmortality following clinical fractures. Osteoporos Int. 2000;11 (7):556-61.
4. US Department of Health and Human Services. Bone health and osteoporosis: a report of the Surgeon General. Rockville, MD: US Department of Health and Human Services, Office of the Surgeon General; 2004.
5. Brauer CA, Coca-PerraillonM, Cutler DM, Rosen AB. Incidence and mortality of hip fractures in the United States. JAMA. 2009 Oct 14;302 (14):1573-9.
6. Mashiba T, Hirano T, Turner CH, Forwood MR, Johnston CC, Burr DB. Suppressed bone turnover by bisphosphonates increases microdamage accumulation and reduces some biomechanical properties in dog rib. J Bone Miner Res. 2000 Apr;15 (4):613-20.
7. Odvina CV, Zerwekh JE, Rao DS, Maalouf N, Gottschalk FA, Pak CY. Severely suppressed bone turnover: a potential complication of alendronate therapy. J Clin Endocrinol Metab. 2005 Mar;90 (3):1294-301. Epub 2004 Dec 14.
8. Sambrook PN, Chen JS, Simpson JM, March LM. Impact of adverse news media on prescriptions for osteoporosis: effect on fractures and mortality. Med J Aust. 2010 Aug 2;193 (3):154-6.
9. Fleisch H, Reszka A, Rodan G, Rogers M. Bisphosphonates: mechanisms of action. In: Bilezikian JP, Raisz LG, Rodan GA, editors. Principles of bone biology. 2nd ed; vol 2. San Diego: Academic Press; 2002. p 1361-85.
10. Gasser AB, Morgan DB, Fleisch HA, Richelle LJ. The influence of two diphosphonates on calcium metabolism in the rat. Clin Sci. 1972 Jul;43 (1):31-45.
11. Jamal SA, Dion N, Ste-Marie LG. Atypical femoral fractures and bone turnover. N Engl J Med. 2011 Sep 29;365 (13):1261-2.
12. Ste-Marie LG, Sod E, Johnson T, Chines A. Five years of treatment with risedronate and its effects on bone safety in women with postmenopausal osteoporosis. Calcif Tissue Int. 2004 Dec;75 (6):469-76. Epub 2004 Oct 14.
13. Black DM, Schwartz AV, Ensrud KE, Cauley JA, Levis S, Quandt SA, Satterfield S, Wallace RB, Bauer DC, Palermo L, Wehren LE, Lombardi A, Santora AC, Cummings SR; FLEX Research Group. Effects of continuing or stopping alendronate after 5 years of treatment: the Fracture Intervention Trial Long-term Extension (FLEX): a randomized trial. JAMA. 2006 Dec 27;296 (24):2927-38.
14. Bennett CL, Nebeker JR, Lyons EA, Samore MH, Feldman MD, McKoy JM, Carson KR, Belknap SM, Trifilio SM, Schumock GT, Yarnold PR, Davidson CJ, Evens AM, Kuzel TM, Parada JP, Cournoyer D, West DP, Sartor O, Tallman MS, Raisch DW. The Research on Adverse Drug Events and Reports (RADAR) project. JAMA. 2005 May 4;293 (17):2131-40.
15. Bennett CL, Luminari S, Nissenson AR, Tallman MS, Klinge SA, McWilliams N, McKoy JM, Kim B, Lyons EA, Trifilio SM, Raisch DW, Evens AM, Kuzel TM, Schumock GT, Belknap SM, Locatelli F, Rossert J, Casadevall N. Pure red-cell aplasia and epoetin therapy. N Engl J Med. 2004 Sep 30;351 (14):1403-8.
16. Bennett CL, Nebeker JR, Yarnold PR, Tigue CC, Dorr DA, McKoy JM, Edwards BJ, Hurdle JF, West DP, Lau DT, Angelotta C, Weitzman SA, Belknap SM, Djulbegovic B, Tallman MS, Kuzel TM, Benson AB, Evens A, Trifilio SM, Courtney DM, Raisch DW. Evaluation of serious adverse drug reactions: a proactive pharmacovigilance program (RADAR) vs safety activities conducted by the Food and Drug Administration and pharmaceutical manufacturers. Arch Intern Med. 2007 May 28;167 (10):1041-9.
17. Bennett CL, Schumock GT, Desai AA, Kwaan HC, Raisch DW, Newlin R, Stadler W. Thalidomide-associated deep vein thrombosis and pulmonary embolism. Am J Med. 2002 Nov;113 (7):603-6.
18. Bennett CL, Tigue CC, Angelotta C, McKoy JM, Edwards BJ. Adverse effects of drugs used to treat hematologic malignancies: surveillance efforts from the Research on Adverse Drug events And Reports project. Semin Thromb Hemost. 2007 Jun;33 (4):365-72.
19. Evans SJ, Waller PC, Davis S. Use of proportional reporting ratios (PRRs) for signal generation from spontaneous adverse drug reaction reports. Pharmacoepidemiol Drug Saf. 2001 Oct-Nov;10 (6):483-6.
20. Hauben M, Zhou X. Quantitative methods in pharmacovigilance: focus on signal detection. Drug Saf. 2003;26 (3):159-86.
21. DuMouchel W, Smith ET, Beasley R, Nelson H, Yang X, Fram D, Almenoff JS. Association of asthma therapy and Churg-Strauss syndrome: an analysis of postmarketing surveillance data. Clin Ther. 2004 Jul;26 (7):1092-1104.
22. Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA, Janecek E, Domecq C, Greenblatt DJ. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther. 1981 Aug;30 (2):239-45.
23. KellyWN. The quality of published adverse drug event reports. Ann Pharmacother. 2003 Dec;37 (12):1774-8.
24. Goh SK, Yang KY, Koh JS, Wong MK, Chua SY, Chua DT, Howe TS. Subtrochanteric insufficiency fractures in patients on alendronate therapy: a caution. J Bone Joint Surg Br. 2007 Mar;89 (3):349-53.
25. Cheung RK, Leung KK, Lee KC, Chow TC. Sequential non-traumatic femoral shaft fractures in a patient on long-term alendronate. Hong Kong Med J. 2007 Dec; 13 (6):485-9.
26. Neviaser AS, Lane JM, Lenart BA, Edobor-Osula F, Lorich DG. Low-energy femoral shaft fractures associated with alendronate use. J Orthop Trauma. 2008 May- Jun;22 (5):346-50.
27. Koh JS, Goh SK, Png MA, Kwek EB, Howe TS. Femoral cortical stress lesions in long-term bisphosphonate therapy: a herald of impending fracture? J Orthop Trauma. 2010 Feb;24 (2):75-81.
28. Abrahamsen B, Eiken P, Eastell R. Subtrochanteric and diaphyseal femur fractures in patients treated with alendronate: a register-based national cohort study. J Bone Miner Res. 2009 Jun;24 (6):1095-102.
29. Schilcher J, Aspenberg P. Incidence of stress fractures of the femoral shaft in women treated with bisphosphonate. Acta Orthop. 2009 Aug;80 (4):413-5.
30. Schilcher J, Micha?elsson K, Aspenberg P. Bisphosphonate use and atypical fractures of the femoral shaft. N Engl J Med. 2011 May 5;364 (18):1728-37.
31. Kim SY, Schneeweiss S, Katz JN, Levin R, Solomon DH. Oral bisphosphonates and risk of subtrochanteric or diaphyseal femur fractures in a populationbased cohort. J Bone Miner Res. 2011 May;26 (5):993-1001. doi: 10.1002/jbmr.288.
32. Feldstein AC, Black D, Perrin N, Rosales AG, Friess D, Boardman D, Dell R, Santora A, Chandler JM, Rix MM, Orwoll E. Incidence and demography of femur fractures with and without atypical features. J Bone Miner Res. 2012 May;27 (5): 977-86. doi: 10.1002/jbmr.1550.
33. Wang Z, Bhattacharyya T. Trends in incidence of subtrochanteric fragility fractures and bisphosphonate use among the US elderly, 1996-2007. J Bone Miner Res. 2011 Mar;26 (3):553-60. doi: 10.1002/jbmr.233.
34. Black DM, Kelly MP, Genant HK, Palermo L, Eastell R, Bucci-Rechtweg C, Cauley J, Leung PC, Boonen S, Santora A, de Papp A, Bauer DC; Fracture Intervention Trial Steering Committee; HORIZON Pivotal Fracture Trial Steering Committee. Bisphosphonates and fractures of the subtrochanteric or diaphyseal femur. N Engl J Med. 2010 May 13;362 (19):1761-71. Epub 2010 Mar 24.
35. Isaacs JD, Shidiak L, Harris IA, Szomor ZL. Femoral insufficiency fractures associated with prolonged bisphosphonate therapy. Clin Orthop Relat Res. 2010 Dec;468 (12):3384-92. Epub 2010 Aug 31.
36. American Dental Association Council on Scientific Affairs. Dental management of patients receiving oral bisphosphonate therapy: expert panel recommendations. J Am Dent Assoc. 2006 Aug;137 (8):1144-50.
37. Edwards BJ. Risedronate exposure 2001-2010. Chicago: Warner Chilcott Labs; 2010.
38. Shane E, Burr D, Ebeling PR, Abrahamsen B, Adler RA, Brown TD, Cheung AM, Cosman F, Curtis JR, Dell R, Dempster D, Einhorn TA, Genant HK, Geusens P, Klaushofer K, Koval K, Lane JM, McKiernan F, McKinney R, Ng A, Nieves J, O'Keefe R, Papapoulos S, Sen HT, van der Meulen MC, Weinstein RS, Whyte M; American Society for Bone and Mineral Research. Atypical subtrochanteric and diaphyseal femoral fractures: report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res. 2010 Nov;25 (11):2267-94.
39. Dell RM, Adams AL, Greene DF, Funahashi TT, Silverman SL, Eisemon EO, Zhou H, Burchette RJ, Ott SM. Incidence of all atypical nontraumatic diaphyseal fractures of the femur. J Bone Miner Res. 2012 Jul 26. doi: 10.1002/jbmr. 1719. [Epub ahead of print].
40. Lenart BA, Neviaser AS, Lyman S, Chang CC, Edobor-Osula F, Steele B, van der Meulen MC, Lorich DG, Lane JM. Association of low-energy femoral fractures with prolonged bisphosphonate use: a case control study. Osteoporos Int. 2009 Aug; 20 (8):1353-62. Epub 2008 Dec 9.
41. Vestergaard P, Schwartz F, Rejnmark L, Mosekilde L. Risk of femoral shaft and subtrochanteric fractures among users of bisphosphonates and raloxifene. Osteoporos Int. 2011 Mar;22 (3):993-1001. Epub 2010 Dec 17.
42. Shakir SA, Layton D. Causal association in pharmacovigilance and pharmacoepidemiology: thoughts on the application of the Austin Bradford-Hill criteria. Drug Saf. 2002;25 (6):467-71.
43. Tan SC, Koh SB, Goh SK, Howe TS. Atypical femoral stress fractures in bisphosphonate-free patients. Osteoporos Int. 2011 Jul;22 (7):2211-2. Epub 2010 Sep 14.
44. Boskey AL, DiCarlo E, Paschalis E, West P, Mendelsohn R. Comparison of mineral quality and quantity in iliac crest biopsies from high- and low-turnover osteoporosis: an FT-IR microspectroscopic investigation. Osteoporos Int. 2005 Dec;16 (12):2031-8. Epub 2005 Aug 9.
45. Boskey AL, Marks SC Jr. Mineral and matrix alterations in the bones of incisorsabsent (ia/ia) osteopetrotic rats. Calcif Tissue Int. 1985 May;37 (3):287-92.
46. Boskey AL, Wright TM, Blank RD. Collagen and bone strength. J BoneMiner Res. 1999 Mar;14 (3):330-5.
47. European Medicines Agency. Assessment report for Fosavance. 2009 Feb 19. http://www.ema.europa.eu/docs/en-GB/document-library/EPAR-Assessment- Report-Variation/human/000619/WC500024252.pdf. Accessed 2010 Nov 20.
48. Whyte MP, McAlister WH, Novack DV, Clements KL, Schoenecker PL, Wenkert D. Bisphosphonate-induced osteopetrosis: novel bone modeling defects, metaphyseal osteopenia, and osteosclerosis fractures after drug exposure ceases. J Bone Miner Res. 2008 Oct;23 (10):1698-707.
49. Whyte MP, Wenkert D, Clements KL, McAlister WH, Mumm S. Bisphosphonateinduced osteopetrosis. N Engl J Med. 2003 Jul 31;349 (5):457-63.
50. Yang KH, Won JH, Yoon HK, Ryu JH, Choo KS, Kim JS. High concentrations of pamidronate in bone weaken the mechanical properties of intact femora in a rat model. Yonsei Med J. 2007 Aug 31;48 (4):653-8.
51. Mashiba T, Mori S, Burr DB, Komatsubara S, Cao Y, Manabe T, Norimatsu H. The effects of suppressed bone remodeling by bisphosphonates on microdamage accumulation and degree of mineralization in the cortical bone of dog rib. J Bone Miner Metab. 2005;23 Suppl:36-42.
52. Boivin G, Meunie PJ. Changes in bone remodeling rate influence the degree of mineralization of bone which is a determinant of bone strength: therapeutic implications. Adv Exp Med Biol. 2001;496:123-7.
53. Somford MP, Draijer FW, Thomassen BJ, Chavassieux PM, Boivin G, Papapoulos SE. Bilateral fractures of the femur diaphysis in a patient with rheumatoid arthritis on long-term treatment with alendronate: clues to the mechanism of increased bone fragility. J Bone Miner Res. 2009 Oct;24 (10):1736-40.
54. Benford HL, McGowan NW, Helfrich MH, Nuttall ME, Rogers MJ. Visualization of bisphosphonate-induced caspase-3 activity in apoptotic osteoclasts in vitro. Bone. 2001 May;28 (5):465-73.
55. Idris AI, Rojas J, Greig IR, Van't Hof RJ, Ralston SH. Aminobisphosphonates cause osteoblast apoptosis and inhibit bone nodule formation in vitro. Calcif Tissue Int. 2008 Mar;82 (3):191-201. Epub 2008 Feb 8.
56. Allen MR, Gineyts E, Leeming DJ, Burr DB, Delmas PD. Bisphosphonates alter trabecular bone collagen cross-linking and isomerization in beagle dog vertebra. Osteoporos Int. 2008 Mar;19 (3):329-37. Epub 2007 Dec 18.
57. Gourion-Arsiquaud S, Allen MR, Burr DB, Vashishth D, Tang SY, Boskey AL. Bisphosphonate treatment modifies canine bone mineral and matrix properties and their heterogeneity. Bone. 2010 Mar;46 (3):666-72. Epub 2009 Nov 17.
58. Viguet-Carrin S, Garnero P, Delmas PD. The role of collagen in bone strength. Osteoporos Int. 2006;17 (3):319-36. Epub 2005 Dec 9.
59. Burr DB. The contribution of the organic matrix to bone's material properties. Bone. 2002 Jul;31 (1):8-11.
60. YamauchiM, Young DR, Chandler GS, Mechanic GL. Cross-linking and new bone collagen synthesis in immobilized and recovering primate osteoporosis. Bone. 1988;9 (6):415-8.
61. Yamauchi M, Woodley DT, Mechanic GL. Aging and cross-linking of skin collagen. Biochem Biophys Res Commun. 1988 Apr 29;152 (2):898-903.
62. Wu P, Koharski C, Nonnenmann H, Vashishth D. Loading on non-enzymatically glycated and damaged bone results in an instantaneous fracture. Trans Orthop Res Soc. 2003;28:404.
63. Gourion-Arsiquaud S, Faibish D, Myers E, Spevak L, Compston J, Hodsman A, Shane E, Recker RR, Boskey ER, Boskey AL. Use of FTIR spectroscopic imaging to identify parameters associated with fragility fracture. J Bone Miner Res. 2009 Sep;24 (9):1565-71.
64. Wang X, Li X, Shen X, Agrawal CM. Age-related changes of noncalcified collagen in human cortical bone. Ann Biomed Eng. 2003 Dec;31 (11):1365-71.
65. Compston J. Pathophysiology of atypical femoral fractures and osteonecrosis of the jaw. Osteoporos Int. 2011 Dec;22 (12):2951-61. Epub 2011 Oct 14. Erratum in: Osteoporos Int. 2012 Feb;23 (2):793.
66. Burr DB. Bone material properties and mineral matrix contributions to fracture risk or age in women and men. J Musculoskelet Neuronal Interact. 2002 Mar;2 (3):201-4.
67. Boskey AL, Spevak L, Weinstein RS. Spectroscopic markers of bone quality in alendronate-treated postmenopausal women. Osteoporos Int. 2009 May;20 (5): 793-800. Epub 2008 Sep 4.
68. Gladnick BP, Donnelly E, Lorich DG, Unnanuntana A, DiCarlo EF, Doty F, Boskey AL, Lane JM, Kane SM, Wolinsky PR. The effects of long-term bisphosphonate use on bone quality. Read at the Annual Meeting of the American Academy of Orthopaedic Surgeons; 2010 Mar 9-13; New Orleans, LA.
69. Geusens P. Bisphosphonates for postmenopausal osteoporosis: determining duration of treatment. Curr Osteoporos Rep. 2009 Mar;7 (1):12-7.
70. Renders GA, Mulder L, Langenbach GE, van Ruijven LJ, van Eijden TM. Biomechanical effect of mineral heterogeneity in trabecular bone. J Biomech. 2008 Sep 18;41 (13):2793-8. Epub 2008 Aug 22.
71. Keaveny TM, Hayes WC. A 20-year perspective on the mechanical properties of trabecular bone. J Biomech Eng. 1993 Nov;115 (4B):534-42.
72. Calton EF, Macleay J, Boskey AL. Fourier transform infrared imaging analysis of cancellous bone in alendronate- and raloxifene-treated osteopenic sheep. Cells Tissues Organs. 2011;194 (2-4):302-6. Epub 2011 May 19.
73. Whyte MP. Hypophosphatasia. In: Scriver CR, Beaudet AL, Valle D, Sly WS, editors. The metabolic & molecular bases of inherited disease. 8th ed. New York: McGraw-Hill; 2001. p 5313-29.
74. Whyte MP. Hypophosphatasia: nature's window on alkaline phosphatase function in humans. In: Bilezikian JP, Raisz LG, Martin TJ, editors. Principles of bone biology. 3rd ed. San Diego, CA: Academic Press; 2008. p 1573-98.
75. Whyte MP. Atypical femoral fractures, bisphosphonates, and adult hypophosphatasia. J Bone Miner Res. 2009 Jun;24 (6):1132-4.
76. Sama AA, Khan SN, Myers ER, Huang RC, Cammisa FP Jr, Sandhu HS, Lane JM. High-dose alendronate uncouples osteoclast and osteoblast function: a study in a rat spine pseudarthrosis model. Clin Orthop Relat Res. 2004 Aug; (425):135-42.
77. Cao Y, Mori S, Mashiba T, Westmore MS, Ma L, Sato M, Akiyama T, Shi L, Komatsubara S, Miyamoto K, Norimatsu H. Raloxifene, estrogen, and alendronate affect the processes of fracture repair differently in ovariectomized rats. J Bone Miner Res. 2002 Dec;17 (12):2237-46.
78. Saito M, Shiraishi A, Ito M, Sakai S, Hayakawa N, Mihara M, Marumo K. Comparison of effects of alfacalcidol and alendronate on mechanical properties and bone collagen cross-links of callus in the fracture repair rat model. Bone. 2010 Apr; 46 (4):1170-9. Epub 2009 Dec 22.
79. Kidd LJ, Cowling NR, Wu AC, Kelly WL, Forwood MR. Bisphosphonate treatment delays stress fracture remodeling in the rat ulna. J Orthop Res. 2011 Dec;29 (12): 1827-33. doi: 10.1002/jor.21464. Epub 2011 May 19.
80. McDonald MM, Dulai S, Godfrey C, Amanat N, Sztynda T, Little DG. Bolus or weekly zoledronic acid administration does not delay endochondral fracture repair but weekly dosing enhances delays in hard callus remodeling. Bone. 2008 Oct;43 (4):653-62. Epub 2008 Jun 3.
81. Shimizu E, Tamasi J, Partridge NC. Alendronate affects osteoblast functions by crosstalk through EphrinB1-EphB. J Dent Res. 2012 Mar;91 (3):268-74. Epub 2011 Dec 15.
82. Peter CP, Cook WO, Nunamaker DM, Provost MT, Seedor JG, Rodan GA. Effect of alendronate on fracture healing and bone remodeling in dogs. J Orthop Res. 1996 Jan;14 (1):74-9.
83. Rozental TD, Vazquez MA, Chacko AT, Ayogu N, Bouxsein ML. Comparison of radiographic fracture healing in the distal radius for patients on and off bisphosphonate therapy. J Hand Surg Am. 2009 Apr;34 (4):595-602.
84. Gerstenfeld LC, Sacks DJ, Pelis M, Mason ZD, Graves DT, Barrero M, Ominsky MS, Kostenuik PJ, Morgan EF, Einhorn TA. Comparison of effects of the bisphosphonate alendronate versus the RANKL inhibitor denosumab on murine fracture healing. J Bone Miner Res. 2009 Feb;24 (2):196-208.
85. Nagahama K, Kanayama M, Togawa D, Hashimoto T, Minami A. Does alendronate disturb the healing process of posterior lumbar interbody fusion? A prospective randomized trial. J Neurosurg Spine. 2011 Apr;14 (4):500-7. Epub 2011 Jan 28.
86. Ha YC, Cho MR, Park KH, Kim SY, Koo KH. Is surgery necessary for femoral insufficiency fractures after long-term bisphosphonate therapy? Clin Orthop Relat Res. 2010 Dec;468 (12):3393-8. Epub 2010 Sep 24.
87. Weil YA, Rivkin G, Safran O, Liebergall M, Foldes AJ. The outcome of surgically treated femur fractures associated with long-term bisphosphonate use. J Trauma. 2011 Jul;71 (1):186-90.
88. Lane J. Subtrochanteric fractures: healing characteristics. In: Edwards BJ, editor. Chicago: ;2010. p
89. Adverse Drug Advisory Committee (ADRAC). Bisphosphonate and fractures medicines summary. 2010 Oct 26.
90. US Food and Drug Administration. FDA Drug Safety Communication: Ongoing safety review of oral bisphosphonates and atypical subtrochanteric femur fractures. 2010 Mar 10. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafety InformationforPatientsandProviders/ucm203891.htm. Accessed 2010 Mar 11.
91. US Food and Drug Administration. Bisphosphonates (osteoporosis drugs): label change - atypical fractures update. 2010 Oct 13. http://www.fda.gov/ Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm229244. htm. Accessed 2010 Oct 19.
92. Health Canada. Safety review of bisphosphonate drugs and the possible risk of rare but serious thigh bone fractures. 2010 Oct 14. http://www.hc-sc.gc. ca/ahc-asc/media/advisories-avis/-2010/2010-175-eng.php. Accessed 2010 Oct 19.
93. Rizzoli R, Akesson K, Bouxsein M, Kanis JA, Napoli N, Papapoulos S, Reginster JY, Cooper C. Subtrochanteric fractures after long-term treatment with bisphosphonates: a European Society on Clinical and Economic Aspects of Osteoporosis and Osteoarthritis, and International Osteoporosis Foundation Working Group Report. Osteoporos Int. 2011 Feb;22 (2):373-90. Epub 2010 Nov 18.
94. Ing-Lorenzini K, Desmeules J, Plachta O, Suva D, Dayer P, Peter R. Low-energy femoral fractures associated with the long-term use of bisphosphonates: a case series from a Swiss university hospital. Drug Saf. 2009;32 (9):775-85. doi: 10. 2165/00002018-200932090-00002.
95. Armamento-Villareal R, Napoli N, Panwar V, Novack D. Suppressed bone turnover during alendronate therapy for high-turnover osteoporosis. N Engl J Med. 2006 Nov 9;355 (19):2048-50.
96. Visekruna M, Wilson D, McKiernan FE. Severely suppressed bone turnover and atypical skeletal fragility. J Clin Endocrinol Metab. 2008 Aug;93 (8):2948-52. Epub 2008 Jun 3.
97. Black DM, Thompson DE, Bauer DC, Ensrud K, Musliner T, Hochberg MC, Nevitt MC, Suryawanshi S, Cummings SR; Fracture Intervention Trial. Fracture risk reduction with alendronate in women with osteoporosis: the Fracture Intervention Trial. FIT Research Group. J Clin Endocrinol Metab. 2000 Nov;85 (11):4118-24.
98. Lasser KE, Allen PD, Woolhandler SJ, Himmelstein DU, Wolfe SM, Bor DH. Timing of new black box warnings and withdrawals for prescription medications. JAMA. 2002 May 1;287 (17):2215-20.
99. Ioannidis JP, Lau J. Completeness of safety reporting in randomized trials: an evaluation of 7 medical areas. JAMA. 2001 Jan 24-31;285 (4):437-43.
100. Juby AG, De Geus-Wenceslau CM. Evaluation of osteoporosis treatment in seniors after hip fracture. Osteoporos Int. 2002 Mar;13 (3):205-10.
101. Kennedy CC, Papaioannou A, Adachi JD. Treating osteoporosis: economic aspects of bisphosphonate therapy. Expert Opin Pharmacother. 2006 Aug; 7 (11):1457-67.
102. Center JR, Bliuc D, Nguyen ND, Nguyen TV, Eisman JA. Osteoporosis medication and reduced mortality risk in elderly women and men. J Clin Endocrinol Metab. 2011 Apr;96 (4):1006-14. Epub 2011 Feb 2.
103. Beaupre LA, Morrish DW, Hanley DA, Maksymowych WP, Bell NR, Juby AG, Majumdar SR. Oral bisphosphonates are associated with reduced mortality after hip fracture. Osteoporos Int. 2011 Mar;22 (3):983-91. Epub 2010 Nov 4.
104. Cree MW, Juby AG, Carriere KC. Mortality and morbidity associated with osteoporosis drug treatment following hip fracture. Osteoporos Int. 2003 Sep;14 (9): 722-7. Epub 2003 Aug 7.
105. Saad F, Lipton A. Clinical benefits and considerations of bisphosphonate treatment in metastatic bone disease. Semin Oncol. 2007 Dec;34 (6 Suppl 4):S17-23.
106. Coleman R. On the horizon: can bisphosphonates prevent bone metastases? Breast. 2007 Dec;16 Suppl 3:S21-7. Epub 2007 Nov 7.
107. Lipton A. Improving progression-free and overall survival in patients with cancer: a potential role for bisphosphonates. Expert Opin Pharmacother. 2011 Apr; 12 (5):749-62. Epub 2011 Jan 20.
108. Lipton A. Zoledronic acid: multiplicity of use across the cancer continuum. Expert Rev Anticancer Ther. 2011 Jul;11 (7):999-1012.
109. Costa L, Harper P, Coleman RE, Lipton A. Anticancer evidence for zoledronic acid across the cancer continuum. Crit Rev Oncol Hematol. 2011 Feb;77 Suppl 1:S31-7.
110. Wilkinson JM, Little DG. Bisphosphonates in orthopedic applications. Bone. 2011 Jul;49 (1):95-102. Epub 2011 Jan 20.
111. Watts NB, Diab DL. Long-term use of bisphosphonates in osteoporosis. Clin Endocrinol Metab. 2010 Apr;95 (4):1555-65. Epub 2010 Feb 19.
112. Edwards BJ, Gounder M, McKoy JM, Boyd I, Farrugia M, Migliorati C, Marx R, Ruggiero S, Dimopoulos M, Raisch DW, Singhal S, Carson K, Obadina E, Trifilio S, West D, Mehta J, Bennett CL. Pharmacovigilance and reporting oversight in US FDA fast-track process: bisphosphonates and osteonecrosis of the jaw. Lancet Oncol. 2008 Dec;9 (12):1166-72.
113. Fisher MJ, Bennett CL, Brown J. Lack of coordinated pharmacovigilance adversely affects veteran care. 2009 National meeting of the Health Services Research and Development Service, Veterans Administration; 2009 May 1-3; Chicago, IL. Paper no. 3005.
114. McKoy JM, Stonecash RE, Cournoyer D, Rossert J, Nissenson AR, Raisch DW, Casadevall N, Bennett CL. Epoetin-associated pure red cell aplasia: past, present, and future considerations. Transfusion. 2008 Aug;48 (8):1754-62. Epub 2008 May 14.
115. Bennett CL, Connors JM, Carwile JM, Moake JL, Bell WR, Tarantolo SR, McCarthy LJ, Sarode R, Hatfield AJ, Feldman MD, Davidson CJ, Tsai HM. Thrombotic thrombocytopenic purpura associated with clopidogrel. N Engl J Med. 2000 Jun 15; 342 (24):1773-7.
116. Russell RG, Croucher PI, Rogers MJ. Bisphosphonates: pharmacology, mechanisms of action and clinical uses. Osteoporos Int. 1999;9 Suppl 2:S66-80.
117. Rodan GA, Reszka AA. Bisphosphonate mechanism of action. Curr Mol Med. 2002 Sep;2 (6):571-7.
118. Hazell L, Shakir SA. Under-reporting of adverse drug reactions: a systematic review. Drug Saf. 2006;29 (5):385-96.