Benefits and risks of bisphosphonate therapy for osteoporosis

Journal of Clinical Endocrinology and Metabolism

Volumn 97, Issue 7, 2012, Pages 2272-2282

  Khosla, Sundeep ^a   Bilezikian, John P ^b   Dempster, David W ^c   Lewiecki, E Michael ^d   Miller, Paul D ^e   Neer, Robert M ^f   Recker, Robert R ^g   Shane, Elizabeth ^b   Shoback, Dolores ^h   Potts, John T ^f  

^a MAYO CLINIC   (United States)

^b Columbia University College of Physicians and Surgeons ^*  (United States)

^c HELEN HAYES HOSPITAL   (United States)

^d UNIVERSITY OF NEW MEXICO SCHOOL OF MEDICINE   (United States)

^e University of Colorado Health Sciences Center   (United States)

^f MASSACHUSETTS GENERAL HOSPITAL   (United States)

^g CREIGHTON UNIVERSITY   (United States)

^h UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALENDRONIC ACID; BISPHOSPHONIC ACID DERIVATIVE; IBANDRONIC ACID; PARACETAMOL; PARATHYROID HORMONE[1-34]; PLACEBO; RISEDRONIC ACID; ZOLEDRONIC ACID;

ARTHRALGIA; BLEEDING; BONE REMODELING; CREATININE BLOOD LEVEL; DRUG ABSORPTION; DRUG EFFICACY; DRUG EXCRETION; DRUG FEVER; DRUG INDUCED HEADACHE; DRUG MECHANISM; DRUG USE; DRUG WITHDRAWAL; ESOPHAGITIS; ESOPHAGUS ULCER; FEMUR SUBTROCHANTERIC FRACTURE; GASTROINTESTINAL SYMPTOM; HEART ATRIUM FIBRILLATION; HIP FRACTURE; HISTOLOGY; HUMAN; JAW OSTEONECROSIS; MALAISE; MYALGIA; NEPHROTOXICITY; OSSIFICATION; OSTEOLYSIS; OSTEOPOROSIS; POSTMENOPAUSE; PRIORITY JOURNAL; REVIEW; RISK ASSESSMENT; RISK BENEFIT ANALYSIS; RISK REDUCTION; SIDE EFFECT; VERTEBRA FRACTURE;

BONE DENSITY CONSERVATION AGENTS; DIPHOSPHONATES; FEMALE; FEMORAL NECK FRACTURES; HUMANS; JAW DISEASES; MALE; MODELS, BIOLOGICAL; OSTEONECROSIS; OSTEOPOROSIS; RISK ASSESSMENT;

EID: 84863587177     PISSN: 0021972X     EISSN: 19457197     Source Type: Journal    
DOI: 10.1210/jc.2012-1027     Document Type: Review

References (97)

1. 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 2010 Atypical subtrochanteric and diaphyseal femoral fractures: report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res 25:2267-2294
2. Cremers S, Papapoulos S 2011 Pharmacology of bisphosphonates. Bone 49:42-49
3. Rogers MJ, Crockett JC, Coxon FP, Mönkkönen J 2011 Biochemical and molecular mechanisms of action of bisphosphonates. Bone 49:34-41
4. Ebetino FH, Hogan AM, Sun S, Tsoumpra MK, Duan X, Triffitt JT, Kwaasi AA, Dunford JE, Barnett BL, Oppermann U, Lundy MW, Boyde A, Kashemirov BA, McKenna CE, Russell RG 2011 The relationship between the chemistry and biological activity of the bisphosphonates. Bone 49:20-33
5. Chavassieux PM, Arlot ME, Reda C, Wei L, Yates AJ, Meunier PJ 1997 Histomorphometric assessment of the long-term effects of alendronate on bone quality and remodeling in patients with osteoporosis. J Clin Invest 100:1475-1480 (Pubitemid 27425772)
6. Burr DB 2002 Targeted and nontargeted remodeling. Bone 30:2-4 (Pubitemid 34044293)
7. Li J, Mashiba T, Burr DB 2001 Bisphosphonate treatment suppresses not only stochastic remodeling but also the targeted repair of microdamage. Calcif Tissue Int 69:281-286 (Pubitemid 33140938)
8. Recker R, Lappe J, Davies KM, Heaney R 2004 Bone remodeling increases substantially in the years after menopause and remains increased in older osteoporosis patients. J Bone Miner Res 19:1628-1633 (Pubitemid 41094325)
9. Eriksen EF, Melsen F, Sod E, Barton I, Chines A 2002 Effects of long-term risedronate on bone quality and bone turnover in women with postmenopausal osteoporosis. Bone 31:620-625 (Pubitemid 35449706)
10. Recker RR, Weinstein RS, Chesnut 3rd CH, Schimmer RC, Mahoney P, Hughes C, Bonvoisin B, Meunier PJ 2004 Histomorphometric evaluation of daily and intermittent oral ibandronate in women with postmenopausal osteoporosis: results from the BONE study. Osteoporos Int 15:231-237 (Pubitemid 38391539)
11. Recker RR, Delmas PD, Halse J, Reid IR, Boonen S, García-Hernandez PA, Supronik J, Lewiecki EM, Ochoa L, Miller P, Hu H, Mesenbrink P, Hartl F, Gasser J, Eriksen EF 2008 Effects of intravenous zoledronic acid once yearly on bone remodeling and bone structure. J Bone Miner Res 23:6-16
12. Bone HG, Hosking D, Devogelaer JP, Tucci JR, Emkey RD, Tonino RP, Rodriguez-Portales JA, Downs RW, Gupta J, Santora AC, Liberman UA 2004 Ten years' experience with alendronate for osteoporosis in postmenopausal women. N Engl J Med 350:1189-1199 (Pubitemid 38339363)
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 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 (Pubitemid 46021497)
14. Miller PD 2008 Anti-resorptives in the management of osteoporosis. Best Pract Res Clin Endocrinol Metab 22:849-868
15. Black DM, Cummings SR, Karpf DB, Cauley JA, Thompson DE, Nevitt MC, Bauer DC, Genant HK, Haskell WL, Marcus R, Ott SM, Torner JC, Quandt SA, Reiss TF, Ensrud KE 1996 Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Lancet 348:1535-1541 (Pubitemid 26411651)
16. Cummings SR, Black DM, Thompson DE, Applegate WB, Barrett-Connor E, Musliner TA, Palermo L, Prineas R, Rubin SM, Scott JC, Vogt T, Wallace R, Yates AJ, LaCroix AZ 1998 Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures. JAMA 280:2077-2082 (Pubitemid 29014065)
17. Reginster J, Minne HW, Sorensen OH, Hooper M, Roux C, Brandi ML, Lund B, Ethgen D, Pack S, Roumagnac I, Eastell R 2000 Randomized trial of the effects of risedronate on vertebral fractures in women with established postmenopausal osteoporosis. Osteoporos Int 11:83-91 (Pubitemid 30099515)
18. Harris ST, Watts NB, Genant HK, McKeever CD, Hangartner T, Keller M, Chesnut 3rd CH, Brown J, Eriksen EF, Hoseyni MS, Axelrod DW, Miller PD 1999 Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis. JAMA 282:1344-1352 (Pubitemid 29483192)
19. Black DM, Delmas PD, Eastell R, Reid IR, Boonen S, Cauley JA, Cosman F, Lakatos P, Leung PC, Man Z, Mautalen C, Mesenbrink P, Hu H, Caminis J, Tong K, Rosario-Jansen T, Krasnow J, Hue TF, Sellmeyer D, Eriksen EF, Cummings SR 2007 Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med 356:1809-1822 (Pubitemid 46698462)
20. Chesnut III CH, Skag A, Christiansen C, Recker R, Stakkestad JA, Hoiseth A, Felsenberg D, Huss H, Gilbride J, Schimmer RC, Delmas PD 2004 Effects of oral ibandronate administered daily or intermittently on fracture risk in postmenopausal osteoporosis. J Bone Miner Res 19:1241-1249 (Pubitemid 41094364)
21. McClung MR, Geusens P, Miller PD, Zippel H, Bensen WG, Roux C, Adami S, Fogelman I, Diamond T, Eastell R, Meunier PJ, Reginster JY 2001 Effect of risedronate on the risk of hip fracture in elderly women. N Engl J Med 344:333-340 (Pubitemid 32107641)
22. Harris ST, Blumentals WA, Miller PD 2008 Ibandronate and the risk of non-vertebral and clinical fractures in women with postmenopausal osteoporosis: results of a meta-analysis of phase III studies. Curr Med Res Opin 24:237-245 (Pubitemid 351160255)
23. Silverman SL, Watts NB, Delmas PD, Lange JL, Lindsay R 2007 Effectiveness of bisphosphonates on nonvertebral and hip fractures in the first year of therapy: the risedronate and alendronate (REAL) cohort study. Osteoporos Int 18:25-34 (Pubitemid 44885493)
24. Silverman SL 2010 Osteoporosis therapies: evidence from healthcare databases and observational population studies. Calcif Tissue Int 87:375-384
25. Miller PD 2010 All bisphosphonates are (or may not be) the same: potential reasons for clinical differences. J Womens Health (Larchmt) 19:665-669
26. Miller PD 2008 Non-vertebral fracture risk reduction with oral bisphosphonates: challenges with interpreting clinical trial data. Curr Med Res Opin 24:107-119 (Pubitemid 351160244)
27. Miller PD 2005 Bone density and markers of bone turnover in predicting fracture risk and how changes in these measures predict fracture risk reduction. Curr Osteoporos Rep 3:103-110
28. Watts NB, Lewiecki EM, Bonnick SL, Laster AJ, Binkley N, Blank RD, Geusens PP, Miller PD, Petak SM, Recker RR, Saag KG, Schousboe J, Siris ES, Bilezikian JP 2009 Perspective: clinical value of monitoring BMD in patients treated with bisphosphonates for osteoporosis. J Bone Miner Res 24:1643-1646
29. Bonnick SL, Shulman L 2006 Monitoring osteoporosis therapy: bone mineral density, bone turnover markers, or both? Am J Med 119(4 Suppl 1):S25-S31
30. Miller PD, Delmas PD, Huss H, Patel KM, Schimmer RC, Adami S, Recker RR 2010 Increases in hip and spine bone mineral density are predictive for vertebral antifracture efficacy with ibandronate. Calcif Tissue Int 87:305-313
31. Davison KS, Siminoski K, Adachi JD, Hanley DA, Goltzman D, Hodsman AB, Josse R, Kaiser S, Olszynski WP, Papaioannou A, Ste-Marie LG, Kendler DL, Tenenhouse A, Brown JP 2006 The effects of antifracture therapies on the components of bone strength: assessment of fracture risk today and in the future. Semin Arthritis Rheum 36:10-21 (Pubitemid 44144500)
32. Fuchs RK, Faillace ME, Allen MR, Phipps RJ, Miller LM, Burr DB 2011 Bisphosphonates do not alter the rate of secondary mineralization. Bone 49:701-705
33. Seeman E, Delmas PD 2006 Bone quality-the material and structural basis of bone strength and fragility. N Engl J Med 354:2250-2261
34. Lewiecki EM, Bilezikian JP, Khosla S, Marcus R, McClung MR, Miller PD, Watts NB, Maricic M 2011 Osteoporosis update from the 2010 Santa Fe Bone Symposium. J Clin Densitom 14:1-21
35. Schafer AL, Vittinghoff E, Ramachandran R, Mahmoudi N, Bauer DC 2010 Laboratory reproducibility of biochemical markers of bone turnover in clinical practice. Osteoporos Int 21:439-445
36. Bergmann P, Body JJ, Boonen S, Boutsen Y, Devogelaer JP, Goemaere S, Kaufman JM, Reginster JY, Gangji V 2009 Evidence-based guidelines for the use of biochemical markers of bone turnover in the selection and monitoring of bisphosphonate treatment in osteoporosis: a consensus document of the Belgian Bone Club. Int J Clin Pract 63:19-26
37. Eastell R, Hannon RA, Wenderoth D, Rodriguez-Moreno J, Sawicki A 2011 Effect of stopping risedronate after long-term treatment on bone turnover. J Clin Endocrinol Metab 96:3367-3373
38. Miller PD, Recker RR, Reginster JY, Riis BJ, Czerwinski E, Masanauskaite D, Kenwright A, Lorenc R, Stakkestad JA, Lakatos P 28 September 2011 Efficacy of monthly oral ibandronate is sustained over 5 years: the MOBILE long-term extension study. Osteoporos Int doi: 10.1007/s00198-011-1773-0
39. Black DM, Reid IR, Boonen S, Bucci-Rechtweg C, Cauley JA, Cosman F, Cummings SR, Hue TF, Lippuner K, Lakatos P, Leung PC, Man Z, Martinez RL, Tan M, Ruzycky ME, Su G, Eastell R 2012 The effect of 3 versus 6 years of zoledronic acid treatment of osteoporosis: a randomized extension to the HORIZON-Pivotal Fracture Trial (PFT). J Bone Miner Res 27:243-254
40. Bliuc D, Nguyen ND, Milch VE, Nguyen TV, Eisman JA, Center JR 2009 Mortality risk associated with low-trauma osteoporotic fracture and subsequent fracture in men and women. JAMA 301:513-521
41. Lyles KW, Colón-Emeric CS, Magaziner JS, Adachi JD, Pieper CF, Mautalen C, Hyldstrup L, Recknor C, Nordsletten L, Moore KA, Lavecchia C, Zhang J, Mesenbrink P, Hodgson PK, Abrams K, Orloff JJ, Horowitz Z, Eriksen EF, Boonen S 2007 Zoledronic acid and clinical fractures and mortality after hip fracture. N Engl J Med 357:1799-1809 (Pubitemid 350044800)
42. Sambrook PN, Cameron ID, Chen JS, March LM, Simpson JM, Cumming RG, Seibel MJ 2011 Oral bisphosphonates are associated with reduced mortality in frail older people: a prospective five-year study. Osteoporos Int 22:2551-2556
43. Lewiecki EM, Miller PD 2007 Renal safety of intravenous bisphosphonates in the treatment of osteoporosis. Expert Opin Drug Saf 6:663-672 (Pubitemid 351308278)
44. Perazella MA, Markowitz GS 2008 Bisphosphonate nephrotoxicity. Kidney Int 74:1385-1393
45. Miller PD 2011 The kidney and bisphosphonates. Bone 49:77-81
46. Boonen S, Sellmeyer DE, Lippuner K, Orlov-Morozov A, Abrams K, Mesenbrink P, Eriksen EF, Miller PD 2008 Renal safety of annual zoledronic acid infusions in osteoporotic postmenopausal women. Kidney Int 74:641-648
47. Morag Y, Morag-Hezroni M, Jamadar DA, Ward BB, Jacobson JA, Zwetchkenbaum SR, Helman J 2009 Bisphosphonate-related osteonecrosis of the jaw: a pictorial review. RadioGraphics 29:1971-1984
48. Schwartz AV, Bauer DC, Cummings SR, Cauley JA, Ensrud KE, Palermo L, Wallace RB, Hochberg MC, Feldstein AC, Lombardi A, Black DM 2010 Efficacy of continued alendronate for fractures in women with and without prevalent vertebral fracture; The FLEX trial. J Bone Miner Res 25:976-982
49. Miller PD, Ward P, Pfister T, Leigh C, Body JJ 2008 Renal tolerability of intermittent intravenous ibandronate treatment for patients with postmenopausal osteoporosis: a review. Clin Exp Rheumatol 26:1125-1133
50. Favus MJ 2010 Bisphosphonates for osteoporosis. N Engl J Med 363:2027-2035
51. Wysowski DK 2009 Reports of esophageal cancer with oral bisphosphonate use. N Engl J Med 360:89-90
52. Green J, Czanner G, Reeves G, Watson J, Wise L, Beral V 2010 Oral bisphosphonates and risk of cancer of oesophagus, stomach, and colorectum: case-control analysis within a UK primary care cohort. BMJ 341:c4444
53. Abrahamsen B, Eiken P, Eastell R 2009 More on reports of esophageal cancer with oral bisphosphonates use. N Engl J Med 360:1789
54. Solomon DH, Patrick A, Brookhart MA 2009 More on reports of esophageal cancer with oral bisphosphonate use. N Engl J Med 360:1789-1790
55. Cardwell CR, Abnet CC, Cantwell MM, Murray LJ 2010 Exposure to oral bisphosphonates and risk of esophageal cancer. JAMA 304: 657-663
56. Hamdy RC 2010 Zoledronic acid: clinical utility and patient considerations in osteoporosis and low bone mass. Drug Des Devel Ther 4:321-335
57. Heckbert SR, Li G, Cummings SR, Smith NL, Psaty BM 2008 Use of alendronate and risk of incident atrial fibrillation in women. Arch Intern Med 168:826-831 (Pubitemid 351649266)
58. Bundred NJ, Campbell ID, Davidson N, DeBoer RH, Eidtmann H, Monnier A, Neven P, von Minckwitz G, Miller JC, Schenk NL, Coleman RE 2008 Effective inhibition of aromatase inhibitor-associated bone loss by zoledronic acid in postmenopausal women with early breast cancer receiving adjuvant letrozole: ZO-FAST Study results. Cancer 112:1001-1010 (Pubitemid 351304583)
59. Hershman DL, McMahon DJ, Crew KD, Cremers S, Irani D, Cucchiara G, Brafman L, Shane E 2008 Zoledronic acid prevents bone loss in premenopausal women undergoing adjuvant chemotherapy for early-stage breast cancer. J Clin Oncol 26:4739-4745
60. Smith MR, Eastham J, Gleason DM, Shasha D, Tchekmedyian S, Zinner N 2003 Randomized controlled trial of zoledronic acid to prevent bone loss in men receiving androgen deprivation therapy for nonmetastatic prostate cancer. J Urol 169:2008-2012 (Pubitemid 36576705)
61. Cummings SR, Schwartz AV, Black DM 2007 Alendronate and atrial fibrillation. N Engl J Med 356:1895-1896
62. Karam R, Camm J, McClung M 2007 Yearly zoledronic acid in postmenopausal osteoporosis. N Engl J Med 357:712-713; author reply 714-715
63. Lewiecki EM, Cooper C, Thompson E, Hartl F, Mehta D, Papapoulos SE 2010 Ibandronate does not increase risk of atrial fibrillation in analysis of pivotal clinical trials. Int J Clin Pract 64:821-826
64. Bunch TJ, Anderson JL, May HT, Muhlestein JB, Horne BD, Crandall BG, Weiss JP, Lappé DL, Osborn JS, Day JD 2009 Relation of bisphosphonate therapies and risk of developing atrial fibrillation. Am J Cardiol 103:824-828
65. Sørensen HT, Christensen S, Mehnert F, Pedersen L, Chapurlat RD, Cummings SR, Baron JA 2008 Use of bisphosphonates among women and risk of atrial fibrillation and flutter: population based case-control study. BMJ 336:813-816 (Pubitemid 351548223)
66. Abrahamsen B, Eiken P, Brixen K 2009 Atrial fibrillation in fracture patients treated with oral bisphosphonates. J Intern Med 265:581-592
67. Grosso A, Douglas I, Hingorani A, MacAllister R, Smeeth L 2009 Oral bisphosphonates and risk of atrial fibrillation and flutter in women: a self-controlled case-series safety analysis. PloS ONE 4:e4720
68. U.S. Food and Drug Administration Update of safety review follow-up to the October 1, 2007 early communication about the ongoing safety review of bisphosphonates http://www.fda.gov/Drugs/DrugSafety/ PostmarketDrugSafetyInformationforPatientsand Providers/ DrugSafetyInformationforHeathcareProfessionals/ucm136201.htm
69. Marx RE 2003 Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic. J Oral Maxillofac Surg 61:1115-1117 (Pubitemid 37064711)
70. Khosla S, Burr D, Cauley J, Dempster DW, Ebeling PR, Felsenberg D, Gagel RF, Gilsanz V, Guise T, Koka S, McCauley LK, McGowan J, McKee MD, Mohla S, Pendrys DG, Raisz LG, Ruggiero SL, Shafer DM, Shum L, Silverman SL, Van Poznak CH, Watts N, Woo SB, Shane E 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 (Pubitemid 351229318)
71. Felsenberg D, Hoffmeister B, Amling M, Mundlos S, Fratzl P 2006 Onkologie: kiefernekrosen nach hoch dosierter bisphosphonattherapie. Dtsch Arztebl 46:A3078-A3080
72. Mavrokokki T, Cheng A, Stein B, Goss A 2007 Nature and frequency of bisphosphonate-associated osteonecrosis of the jaws in Australia. J Oral Maxillofac Surg 65:415-423 (Pubitemid 46343586)
73. Lo JC, O'Ryan FS, Gordon NP, Yang J, Hui RL, Martin D, Hutchinson M, Lathon PV, Sanchez G, Silver P, Chandra M, McCloskey CA, Staffa JA, Willy M, Selby JV, Go AS 2010 Prevalence of osteonecrosis of the jaw in patients with oral bisphosphonate exposure. J Oral Maxillofac Surg 68:243-253
74. Khan AA, Rios LP, Sándor GK, Khan N, Peters E, Rahman MO, Clokie CM, Dore E, Dubois S 2011 Bisphosphonate-associated osteonecrosis of the jaw in Ontario: a survey of oral and maxillofacial surgeons. J Rheumatol 38:1396-1402
75. Marx RE, Cillo Jr JE, Ulloa JJ 2007 Oral bisphosphonate-induced osteonecrosis: risk factors, prediction of risk using serum CTX testing, prevention and treatment. J Oral Maxillofac Surg 65:2397-2410 (Pubitemid 350100982)
76. Lau AN, Adachi JD 2009 Resolution of osteonecrosis of the jaw after teriparatide [recombinant human PTH-(1-34)] therapy. J Rheumatol 36:1835-1837
77. Cheung A, Seeman E 2010 Teriparatide therapy for alendronate-associated osteonecrosis of the jaw. N Engl J Med 363:2473-2474
78. Nieves JW, Bilezikian JP, Lane JM, Einhorn TA, Wang Y, Steinbuch M, Cosman F 2010 Fragility fractures of the hip and femur: incidence and patient characteristics. Osteoporos Int 21:399-408
79. Wang Z, Bhattacharyya T 2011 Trends in incidence of subtrochanteric fragility fractures and bisphosphonate use among the US elderly. J Bone Miner Res 26:553-560
80. Giusti A, Hamdy NA, Dekkers OM, Ramautar SR, Dijkstra S, Papapoulos SE 2011 Atypical fractures and bisphosphonate therapy: a cohort study of patients with femoral fracture with radiographic adjudication of fracture site and features. Bone 48:966-971
81. Lenart BA, Neviaser AS, Lyman S, Chang CC, Edobor-Osula F, Steele B, van der Meulen MC, Lorich DG, Lane JM 2009 Association of low-energy femoral fractures with prolonged bisphosphonate use: a case control study. Osteoporos Int 20:1353-1362
82. Schilcher J, Aspenberg P 2009 Incidence of stress fractures of the femoral shaft in women treated with bisphosphonate. Acta Orthop 80:413-415
83. 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 2010 Bisphosphonates and fractures of the subtrochanteric or diaphyseal femur. N Engl J Med 362:1761-1771
84. Abrahamsen B, Eiken P, 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
85. Kim SY, Schneeweiss S, Katz JN, Levin R, Solomon DH 2011 Oral bisphosphonates and risk of subtrochanteric or diaphyseal femur fractures in a population-based cohort. J Bone Miner Res 26:993-1001
86. Vestergaard P, Schwartz F, Rejnmark L, Mosekilde L 2011 Risk of femoral shaft and subtrochanteric fractures among users of bisphosphonates and raloxifene. Osteoporos Int 22:993-1001
87. Abrahamsen B, Eiken P, Eastell R 2010 Cumulative alendronate dose and the long-term absolute risk of subtrochanteric and diaphyseal femur fractures: a register-based national cohort analysis. J Clin Endocrinol Metab 95:5258-5265
88. Park-Wyllie LY, Mamdani MM, Juurlink DN, Hawker GA, Gunraj N, Austin PC, Whelan DB, Weiler PJ, Laupacis A 2011 Bisphosphonate use and the risk of subtrochanteric or femoral shaft fractures in older women. JAMA 305:783-789
89. Schilcher J, Michaëlsson K, Aspenberg P 2011 Bisphosphonate use and atypical fractures of the femoral shaft. N Engl J Med 364:1728-1737
90. Carvalho NN, Voss LA, Almeida MO, Salgado CL, Bandeira F 2011 Atypical femoral fractures during prolonged use of bisphosphonates: short-term responses to strontium ranelate and teriparatide. J Clin Endocrinol Metab 96:2675-2680
91. Gomberg SJ, Wustrack RL, Napoli N, Arnaud CD, Black DM 2011 Teriparatide, vitamin D, and calcium healed bilateral subtrochanteric stress fractures in a postmenopausal woman with a 13-year history of continuous alendronate therapy. J Clin Endocrinol Metab 96:1627-1632
92. Compston J 2011 Pathophysiology of atypical femoral fractures and osteonecrosis of the jaw. Osteoporos Int 22:2951-2961
93. Bonnick SL 2011 Going on a drug holiday? J Clin Densitom 14: 377-383
94. Watts NB, Diab DL 2010 Long-term use of bisphosphonates in osteoporosis. J Clin Endocrinol Metab 95:1555-1565
95. 2004 The frequency of bone disease. Bone health and osteoporosis: a report of the Surgeon General. Chap 4. Rockville, MD: U.S. Department of Health and Human Services, Office of the Surgeon General; 68-87
96. Siris ES, Pasquale MK, Wang Y, Watts NB 2011 Estimating bisphosphonate use and fracture reduction among US women aged 45 years and older. J Bone Miner Res 26:3-11
97. Dawson-Hughes B 2008 A revised clinician's guide to the prevention and treatment of osteoporosis. J Clin Endocrinol Metab 93:2463-2465 (Pubitemid 352008504)