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Review

Bisphosphonates in the treatment of osteoporosis: a review of skeletal safety concerns

Pages 59-71 | Received 18 Jul 2016, Accepted 31 Oct 2016, Published online: 15 Nov 2016

References

  • Fearing Drugs’ Rare Side Effects, Millions Take Their Chances with Osteoporosis. 2016. [cited 2016 June 1]. Available from: http://mobile.nytimes.com/2016/06/02/health/osteoporosis-drugs-bones.html?_r=0&referer=http://www.jwatch.org/fw111641/2016/06/03/patients-avoiding-newer-osteoporosis-drugs-because-rare?query=topic_bone&jwd=000013026366&jspc=END
  • Kim SC, Kim DH, Mogun H, et al. Impact of the US Food and Drug Administration’s safety-related announcements on the use of bisphosphonates after hip fracture. J Bone Miner Res. 2016;31:1536–1540.
  • Jha S, Wang Z, Laucis N, et al. Trends in media reports, oral bisphosphonate prescriptions, and hip fractures 1996-2012: an ecological analysis. J Bone Miner Res. 2015;30:2179–2187.
  • Solomon DH, Johnston SS, Boytsov NN, et al. Osteoporosis medication use after hip fracture in U.S. patients between 2002 and 2011. J Bone Miner Res. 2014;29:1929–1937.
  • Kim SC, Kim MS, Sanfelix-Gimeno G, et al. Use of osteoporosis medications after hospitalization for hip fracture: a cross-national study. Am J Med. 2015;128:519–26 e1.
  • Statement from American Society for Bone and Mineral Research, National Osteoporosis Foundation and National Bone Health Alliance: Nation’s Scientific and Medical Bone Health Experts Call for Action On Dangers of Not Treating Osteoporosis More Aggressively. National Osteoporosis Foundation, National Bone Health Alliance, The American Society of Bone and Mineral Research. [cited 2016 June 24]. Available from: http://us12.campaign-archive1.com/?u=a33be46687c05945eac5c7158&id=6f8d74997d&e=[UNIQID]
  • Watts NB, Diab DL. Long-term use of bisphosphonates in osteoporosis. J Clin Endocrinol Metab. 2010;95:1555–1565.
  • Russell RG. Bisphosphonates: the first 40 years. Bone. 2011;49:2–19.
  • Reaction: Osteonecrosis. Drugs: Pamidronate (Aredia) and Zoledronic Acid (Zometa). 2003. [cited 2016 July 14]. Available from: http://www.fda.gov/ohrms/dockets/ac/05/briefing/2005-4095B2_03_03-FDA-TAB2.pdf
  • Early Communication of an Ongoing Safety Review on Bisphosphonates: Alendronate (Fosamax, Fosamax Plus D), Etidronate (Didronel), Ibandronate (Boniva), Pamidronate (Aredia), Risedronate (Actonel, Actonel W/Calcium), Tiludronate (Skelid), and Zoledronic acid (Reclast, Zometa). 2007. [cited 2016 July 14]. Available from: http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm070303.htm
  • Update of Safety Review Follow-up to the October 1, 2007 early communication about the ongoing safety review of bisphosphonates. 2008. [cited 2016 July 14. Available from: http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm136201.htm
  • FDA Drug Safety Communication: safety update for osteoporosis drugs, bisphosphonates, and atypical fractures. 2010. [cited 2016 July 14]. Available from: http://www.fda.gov/Drugs/DrugSafety/ucm229009.htm.
  • FDA Drug Safety Communication: ongoing safety review of oral bisphosphonates and atypical subtrochanteric femur fractures. 2010. [cited 2016 July 14]. Available from: http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm203891.htm
  • Marx RE. Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic. J Oral Maxillofac Surg. 2003;61:1115–1117.
  • Ruggiero SL, Mehrotra B, Rosenberg TJ, et al. Osteonecrosis of the jaws associated with the use of bisphosphonates: a review of 63 cases. J Oral Maxillofac Surg. 2004;62:527–534.
  • McLeod NM, Brennan PA, Ruggiero SL. Bisphosphonate osteonecrosis of the jaw: a historical and contemporary review. Surgeon. 2012;10:36–42.
  • Ruggiero SL, Dodson TB, Fantasia J, et al. American Association of Oral and Maxillofacial Surgeons position paper on medication-related osteonecrosis of the jaw – 2014 update. J Oral Maxillofac Surg. 2014;72:1938–1956.
  • Khan AA, Morrison A, Hanley DA, et al. Diagnosis and management of osteonecrosis of the jaw: a systematic review and international consensus. J Bone Miner Res. 2015;30:3–23.
  • Boff RC, Salum FG, Figueiredo MA, et al. Important aspects regarding the role of microorganisms in bisphosphonate-related osteonecrosis of the jaws. Arch Oral Biol. 2014;59:790–799.
  • Khan A, Morrison A, Cheung A, et al. Osteonecrosis of the jaw (ONJ): diagnosis and management in 2015. Osteoporos Int. 2016;27:853–859.
  • Schipmann S, Metzler P, Rossle M, et al. Osteopathology associated with bone resorption inhibitors – which role does Actinomyces play? A presentation of 51 cases with systematic review of the literature. J Oral Pathol Med. 2013;42:587–593.
  • De Ceulaer J, Tacconelli E, Vandecasteele SJ. Actinomyces osteomyelitis in bisphosphonate-related osteonecrosis of the jaw (BRONJ): the missing link? Eur J Clin Microbiol Infect Dis. 2014;33:1873–1880.
  • Fliefel R, Troltzsch M, Kuhnisch J, et al. Treatment strategies and outcomes of bisphosphonate-related osteonecrosis of the jaw (BRONJ) with characterization of patients: a systematic review. Int J Oral Maxillofac Surg. 2015;44:568–585.
  • Solomon DH, Mercer E, Woo SB, et al. Defining the epidemiology of bisphosphonate-associated osteonecrosis of the jaw: prior work and current challenges. Osteoporos Int. 2013;24:237–244.
  • Hellstein JW, Adler RA, Edwards B, et al. Managing the care of patients receiving antiresorptive therapy for prevention and treatment of osteoporosis: executive summary of recommendations from the American Dental Association Council on Scientific Affairs. J Am Dent Assoc. 2011;142:1243–1251.
  • O’Ryan FS, Lo JC. Bisphosphonate-related osteonecrosis of the jaw in patients with oral bisphosphonate exposure: clinical course and outcomes. J Oral Maxillofac Surg. 2012;70:1844–1853.
  • Lo JC, O’Ryan FS, Gordon NP, et al. Prevalence of osteonecrosis of the jaw in patients with oral bisphosphonate exposure. J Oral Maxillofac Surg. 2010;68:243–253.
  • Kuhl S, Walter C, Acham S, et al. Bisphosphonate-related osteonecrosis of the jaws – a review. Oral Oncol. 2012;48:938–947.
  • Baillargeon J, Kuo YF, Lin YL, et al. Osteonecrosis of the jaw in older osteoporosis patients treated with intravenous bisphosphonates. Ann Pharmacother. 2011;45:1199–1206.
  • Pazianas M, Miller P, Blumentals WA, et al. A review of the literature on osteonecrosis of the jaw in patients with osteoporosis treated with oral bisphosphonates: prevalence, risk factors, and clinical characteristics. Clin Ther. 2007;29:1548–1558.
  • Izzotti A, Menini M, Pulliero A, et al. Biphosphonates-associated osteonecrosis of the jaw: the role of gene-environment interaction. J Prev Med Hyg. 2013;54:138–145.
  • Bejhed RS, Kharazmi M, Hallberg P. Identification of risk factors for bisphosphonate-associated atypical femoral fractures and osteonecrosis of the jaw in a pharmacovigilance database. Ann Pharmacother. 2016;50:616–624.
  • Di Fede O, Fusco V, Matranga D, et al. Osteonecrosis of the jaws in patients assuming oral bisphosphonates for osteoporosis: a retrospective multi-hospital-based study of 87 Italian cases. Eur J Intern Med. 2013;24:784–790.
  • Kharazmi M, Hallberg P, Warfvinge G, et al. Risk of atypical femoral fractures and osteonecrosis of the jaw associated with alendronate use compared with other oral bisphosphonates. Rheumatology (Oxford). 2014;53:1911–1913.
  • Oteri G, Bramanti E, Nigrone V, et al. Decayed, missing, and filled teeth index and periodontal health in osteoporotic patients affected by BRONJ: an observational study. J Osteoporos. 2013;2013:231289.
  • Zhang X, Hamadeh IS, Song S, et al. Osteonecrosis of the jaw in the United States Food and Drug Administration’s Adverse Event Reporting System (FAERS). J Bone Miner Res. 2016;31:336–340.
  • Vescovi P, Merigo E, Meleti M, et al. Bisphosphonates-related osteonecrosis of the jaws: a concise review of the literature and a report of a single-centre experience with 151 patients. J Oral Pathol Med. 2012;41:214–221.
  • Pichardo SE, van Merkesteyn JP. Bisphosphonate related osteonecrosis of the jaws: spontaneous or dental origin? Oral Surg Oral Med Oral Pathol Oral Radiol. 2013;116:287–292.
  • Fedele S, Bedogni G, Scoletta M, et al. Up to a quarter of patients with osteonecrosis of the jaw associated with antiresorptive agents remain undiagnosed. Br J Oral Maxillofac Surg. 2015;53:13–17.
  • Bedogni A, Fedele S, Bedogni G, et al. Staging of osteonecrosis of the jaw requires computed tomography for accurate definition of the extent of bony disease. Br J Oral Maxillofac Surg. 2014;52:603–608.
  • Nisi M, La Ferla F, Karapetsa D, et al. Risk factors influencing BRONJ staging in patients receiving intravenous bisphosphonates: a multivariate analysis. Int J Oral Maxillofac Surg. 2015;44:586–591.
  • Ristow O, Otto S, Troeltzsch M, et al. Treatment perspectives for medication-related osteonecrosis of the jaw (MRONJ). J Craniomaxillofac Surg. 2015;43:290–293.
  • Adler RA, El-Hajj Fuleihan G, Bauer DC, et al. Managing osteoporosis in patients on long-term bisphosphonate treatment: report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res. 2016;31:16–35.
  • Moretti F, Pelliccioni GA, Montebugnoli L, et al. A prospective clinical trial for assessing the efficacy of a minimally invasive protocol in patients with bisphosphonate-associated osteonecrosis of the jaws. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2011;112:777–782.
  • Rupel K, Ottaviani G, Gobbo M, et al. A systematic review of therapeutical approaches in bisphosphonates-related osteonecrosis of the jaw (BRONJ). Oral Oncol. 2014;50:1049–1057.
  • Scoletta M, Arata V, Arduino PG, et al. Tooth extractions in intravenous bisphosphonate-treated patients: a refined protocol. J Oral Maxillofac Surg. 2013;71:994–999.
  • Hasegawa T, Ri S, Umeda M, et al. The observational study of delayed wound healing after tooth extraction in patients receiving oral bisphosphonate therapy. J Craniomaxillofac Surg. 2013;41:558–563.
  • Shane E, Burr D, Abrahamsen B, et al. Atypical subtrochanteric and diaphyseal femoral fractures: second report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res. 2014;29:1–23.
  • Dell RM, Adams AL, Greene DF, et al. Incidence of atypical nontraumatic diaphyseal fractures of the femur. J Bone Miner Res. 2012;27:2544–2550.
  • 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;26:553–560.
  • Lee YK, Ha YC, Park C, et al. Bisphosphonate use and increased incidence of subtrochanteric fracture in South Korea: results from the National Claim Registry. Osteoporos Int. 2013;24:707–711.
  • Hsiao FY, Huang WF, Chen YM, et al. Hip and subtrochanteric or diaphyseal femoral fractures in alendronate users: a 10-year, nationwide retrospective cohort study in Taiwanese women. Clin Ther. 2011;33:1659–1667.
  • Thompson RN, Phillips JR, McCauley SH, et al. Atypical femoral fractures and bisphosphonate treatment: experience in two large United Kingdom teaching hospitals. J Bone Joint Surg Br. 2012;94:385–390.
  • Gedmintas L, Solomon DH, Kim SC. Bisphosphonates and risk of subtrochanteric, femoral shaft, and atypical femur fracture: a systematic review and meta-analysis. J Bone Miner Res. 2013;28:1729–1737.
  • Lee S, Yin RV, Hirpara H, et al. Increased risk for atypical fractures associated with bisphosphonate use. Fam Pract. 2015;32:276–281.
  • Liu J, Zhang HX, Lu XX, et al. Bisphosphonates and risk of subtrochanteric, femoral shaft, and atypical femur fracture: sensitivity and trim and fill studies. Genet Test Mol Biomarkers. 2014;18:117–122.
  • Schilcher J, Michaelsson K, Aspenberg P. Bisphosphonate use and atypical fractures of the femoral shaft. N Engl J Med. 2011;364:1728–1737.
  • Schilcher J, Koeppen V, Aspenberg P, et al. Risk of atypical femoral fracture during and after bisphosphonate use. Acta Orthop. 2015;86:100–107.
  • Erviti J, Alonso A, Oliva B, et al. Oral bisphosphonates are associated with increased risk of subtrochanteric and diaphyseal fractures in elderly women: a nested case-control study. BMJ Open. 2013;3:e002091. doi:10.1136/bmjopen-2012-002091.
  • Abrahamsen B, Eiken P, Prieto-Alhambra D, et al. Risk of hip, subtrochanteric, and femoral shaft fractures among mid and long term users of alendronate: nationwide cohort and nested case-control study. BMJ. 2016;353:i3365.
  • Abrahamsen B, Eiken P, Eastell R. 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. 2010;95:5258–5265.
  • Feldstein AC, Black D, Perrin N, et al. Incidence and demography of femur fractures with and without atypical features. J Bone Miner Res. 2012;27:977–986.
  • Rydholm A. Highly different risk estimates for atypical femoral fracture with use of bisphosphonates – debate must be allowed! Acta Orthop. 2012;83:319–320.
  • Meier RP, Perneger TV, Stern R, et al. Increasing occurrence of atypical femoral fractures associated with bisphosphonate use. Arch Intern Med. 2012;172:930–936.
  • Meling T, Nawab A, Harboe K, et al. A typical femoral fractures in elderly women: a fracture registry-based cohort study. Bone Joint J. 2014;96-B:1035–1040.
  • Tamminen IS, Yli-Kyyny T, Isaksson H, et al. Incidence and bone biopsy findings of atypical femoral fractures. J Bone Miner Metab. 2013;31:585–594.
  • Schilcher J, Koeppen V, Ranstam J, et al. Atypical femoral fractures are a separate entity, characterized by highly specific radiographic features. A comparison of 59 cases and 218 controls. Bone. 2013;52:389–392.
  • Juby AG, Crowther S, Cree M. Identifying atypical femoral fractures – a retrospective review. Calcif Tissue Int. 2014;95:405–412.
  • Schilcher J, Sandberg O, Isaksson H, et al. Histology of 8 atypical femoral fractures: remodeling but no healing. Acta Orthop. 2014;85:280–286.
  • Aspenberg P. Denosumab and atypical femoral fractures. Acta Orthop. 2014;85:1.
  • Bottai V, Giannotti S, Dell’osso G, et al. Atypical femoral fractures: retrospective radiological study of 319 femoral fractures and presentation of clinical cases. Osteoporos Int. 2014;25:993–997.
  • Donnelly E, Meredith DS, Nguyen JT, et al. Reduced cortical bone compositional heterogeneity with bisphosphonate treatment in postmenopausal women with intertrochanteric and subtrochanteric fractures. J Bone Miner Res. 2012;27:672–678.
  • Aspenberg P, Schilcher J. Atypical femoral fractures, bisphosphonates, and mechanical stress. Curr Osteoporos Rep. 2014;12:189–193.
  • Ettinger B, Burr DB, Ritchie RO. Proposed pathogenesis for atypical femoral fractures: lessons from materials research. Bone. 2013;55:495–500.
  • van der Meulen MC, Boskey AL. Atypical subtrochanteric femoral shaft fractures: role for mechanics and bone quality. Arthritis Res Ther. 2012;14:220.
  • Patntirapong S, Singhatanadgit W, Arphavasin S. Alendronate-induced atypical bone fracture: evidence that the drug inhibits osteogenesis. J Clin Pharm Ther. 2014;39:349–353.
  • Kharazmi M, Michaelsson K, Hallberg P. Prodromal symptoms in patients with bisphosphonate-associated atypical fractures of the femur. J Bone Miner Metab. 2015;33:516–522.
  • Edwards BJ, Bunta AD, Lane J, et al. 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. J Bone Joint Surg Am. 2013;95:297–307.
  • Schneider JP, Hinshaw WB, Su C, et al. Atypical femur fractures: 81 individual personal histories. J Clin Endocrinol Metab. 2012;97:4324–4328.
  • Kang JS, Won YY, Kim JO, et al. Atypical femoral fractures after anti-osteoporotic medication: a Korean multicenter study. Int Orthop. 2014;38:1247–1253.
  • Zanchetta MB, Diehl M, Buttazzoni M, et al. Assessment of bone microarchitecture in postmenopausal women on long-term bisphosphonate therapy with atypical fractures of the femur. J Bone Miner Res. 2014;29:999–1004.
  • Rosenberg ZS, La Rocca Vieira R, Chan SS, et al. Bisphosphonate-related complete atypical subtrochanteric femoral fractures: diagnostic utility of radiography. AJR Am J Roentgenol. 2011;197:954–960.
  • Marcano A, Taormina D, Egol KA, et al. Are race and sex associated with the occurrence of atypical femoral fractures? Clin Orthop Relat Res. 2014;472:1020–1027.
  • Saita Y, Ishijima M, Mogami A, et al. The incidence of and risk factors for developing atypical femoral fractures in Japan. J Bone Miner Metab. 2015;33:311–318.
  • Franceschetti P, Bondanelli M, Caruso G, et al. Risk factors for development of atypical femoral fractures in patients on long-term oral bisphosphonate therapy. Bone. 2013;56:426–431.
  • Shkolnikova J, Flynn J, Choong P. Burden of bisphosphonate-associated femoral fractures. ANZ J Surg. 2013;83:175–181.
  • Wang Z, Ward MM, Chan L, et al. Adherence to oral bisphosphonates and the risk of subtrochanteric and femoral shaft fractures among female Medicare beneficiaries. Osteoporos Int. 2014;25:2109–2116.
  • Velasco S, Kim S, Bleakney R, et al. The clinical characteristics of patients with hip fractures in typical locations and atypical femoral fractures. Arch Osteoporos. 2014;9:171.
  • Lovy AJ, Koehler SM, Keswani A, et al. Atypical femur fracture during bisphosphonate drug holiday: a case series. Osteoporos Int. 2015;26:1755–1758.
  • Markman LH, Allison MB, Rosenberg ZS, et al. A retrospective review of patients with atypical femoral fractures while on long-term bisphosphonates: including pertinent biochemical and imaging studies. Endocr Pract. 2013;19:456–461.
  • Ng AC, Koh JS, Howe TS. Vitamin D and atypical femoral fractures. Osteoporos Int. 2013;24:1767.
  • Koeppen VA, Schilcher J, Aspenberg P. Atypical fractures do not have a thicker cortex. Osteoporos Int. 2012;23:2893–2896.
  • Chen F, Wang Z, Bhattacharyya T. Absence of femoral cortical thickening in long-term bisphosphonate users: implications for atypical femur fractures. Bone. 2014;62:64–66.
  • Niimi R, Kono T, Nishihara A, et al. Cortical thickness of the femur and long-term bisphosphonate use. J Bone Miner Res. 2015;30:225–231.
  • Unnanuntana A, Ashfaq K, Ton QV, et al. The effect of long-term alendronate treatment on cortical thickness of the proximal femur. Clin Orthop Relat Res. 2012;470:291–298.
  • Mohan PC, Howe TS, Koh JS, et al. Radiographic features of multifocal endosteal thickening of the femur in patients on long-term bisphosphonate therapy. Eur Radiol. 2013;23:222–227.
  • Taormina DP, Marcano AI, Karia R, et al. Symptomatic atypical femoral fractures are related to underlying hip geometry. Bone. 2014;63:1–6.
  • Saita Y, Ishijima M, Mogami A, et al. The fracture sites of atypical femoral fractures are associated with the weight-bearing lower limb alignment. Bone. 2014;66:105–110.
  • Bronson WH, Kaye ID, Egol KA. Atypical femur fractures: a review. Curr Osteoporos Rep. 2014;12:446–453.
  • Miyakoshi N, Aizawa T, Sasaki S, et al. Healing of bisphosphonate-associated atypical femoral fractures in patients with osteoporosis: a comparison between treatment with and without teriparatide. J Bone Miner Metab. 2015;33:553–559.
  • Teo BJ, Koh JS, Goh SK, et al. Post-operative outcomes of atypical femoral subtrochanteric fracture in patients on bisphosphonate therapy. Bone Joint J. 2014;96-B:658–664.
  • La Rocca Vieira R, Rosenberg ZS, Allison MB, et al. Frequency of incomplete atypical femoral fractures in asymptomatic patients on long-term bisphosphonate therapy. AJR Am J Roentgenol. 2012;198:1144–1151.
  • Ward WG Sr., Carter CJ, Wilson SC, et al. Femoral stress fractures associated with long-term bisphosphonate treatment. Clin Orthop Relat Res. 2012;470:759–765.
  • Napoli N, Schwartz AV, Palermo L, et al. Risk factors for subtrochanteric and diaphyseal fractures: the study of osteoporotic fractures. J Clin Endocrinol Metab. 2013;98:659–667.
  • Kharazmi M, Hallberg P. Bisphosphonate-associated atypical femoral fractures and one-year mortality. Ups J Med Sci. 2014;119:357–358.
  • McClung M, Harris ST, Miller PD, et al. Bisphosphonate therapy for osteoporosis: benefits, risks, and drug holiday. Am J Med. 2013;126:13–20.
  • Rizzoli R, Reginster JY, Boonen S, et al. Adverse reactions and drug-drug interactions in the management of women with postmenopausal osteoporosis. Calcif Tissue Int. 2011;89:91–104.
  • Bolland MJ, Grey AB, Gamble GD, et al. Effect of osteoporosis treatment on mortality: a meta-analysis. J Clin Endocrinol Metab. 2010;95:1174–1181.
  • Cosman F, De Beur SJ, LeBoff MS, et al. Clinician’s guide to prevention and treatment of osteoporosis. Osteoporos Int. 2014;25:2359–2381.
  • Chapurlat R. Cathepsin K inhibitors and antisclerostin antibodies. The next treatments for osteoporosis? Joint Bone Spine. 2016;83:254–256.
  • Selga J, Nunez JH, Minguell J, et al. Simultaneous bilateral atypical femoral fracture in a patient receiving denosumab: case report and literature review. Osteoporos Int. 2016;27:827–832.
  • Papapoulos S, Lippuner K, Roux C, et al. The effect of 8 or 5 years of denosumab treatment in postmenopausal women with osteoporosis: results from the FREEDOM extension study. Osteoporos Int. 2015;26:2773–2783.
  • Bone HG, Chapurlat R, Brandi ML, et al. The effect of three or six years of denosumab exposure in women with postmenopausal osteoporosis: results from the FREEDOM extension. J Clin Endocrinol Metab. 2013;98:4483–4492.
  • Drampalos E, Skarpas G, Barbounakis N, et al. Atypical femoral fractures bilaterally in a patient receiving denosumab. Acta Orthop. 2014;85:3–5.
  • Khow KS, Yong TY. Atypical femoral fracture in a patient treated with denosumab. J Bone Miner Metab. 2015;33:355–358.
  • Thompson RN, Armstrong CL, Heyburn G. Bilateral atypical femoral fractures in a patient prescribed denosumab - a case report. Bone. 2014;61:44–47.
  • Neuprez A, Coste S, Rompen E, et al. Osteonecrosis of the jaw in a male osteoporotic patient treated with denosumab. Osteoporos Int. 2014;25:393–395.
  • Rachner TD, Platzbecker U, Felsenberg D, et al. Osteonecrosis of the jaw after osteoporosis therapy with denosumab following long-term bisphosphonate therapy. Mayo Clin Proc. 2013;88:418–419.

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