Semin Musculoskelet Radiol 2016; 20(04): 376-381
DOI: 10.1055/s-0036-1593766
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Atypical Fractures Following Bisphosphonate Therapy

Rati N. Patel
3   Department of Radiology, Cleveland Clinic, Cleveland, Ohio
,
Anwar Ashraf
1   Department Musculoskeletal Radiology, Cleveland Clinic Imaging Institute, Cleveland, Ohio
,
Murali Sundaram
2   Department of Radiology, Lerner College of Medicine and Case Western Reserve University, Cleveland, Ohio
3   Department of Radiology, Cleveland Clinic, Cleveland, Ohio
› Author Affiliations
Further Information

Publication History

Publication Date:
14 November 2016 (online)

Abstract

Bisphosphonates have been widely used in the treatment of osteoporosis with well-documented long-term efficacy and safety, particularly in postmenopausal patients. But over the past decade, low-energy atypical subtrochanteric and proximal diaphyseal femoral fractures have emerged as an unexpected complication of prolonged bisphosphonate use. To the radiologist unfamiliar with this entity, the findings may be subtle and often missed, potentially evolving from an early incomplete fracture to a displaced complete fracture with a delay in diagnosis.

In such instances where the radiographic findings are negative or equivocal and patients present with prodromal symptoms of aching or dull groin or thigh pain, additional work-up with advanced imaging techniques, such as magnetic resonance imaging, computed tomography, or bone scintigraphy, may prove diagnostic owing to their multiplanar capabilities and earlier detection of subtle periosteal changes. It is imperative that radiologists develop a search pattern to help identify such fractures and consider imaging evaluation of the contralateral extremity in suspected cases with prodromal symptoms to assess for an incomplete asymptomatic or minimally symptomatic fracture.

 
  • References

  • 1 Crandall CJ, Newberry SJ, Diamant A , et al. Comparative effectiveness of pharmacologic treatments to prevent fractures: an updated systematic review. Ann Intern Med 2014; 161 (10) 711-723
  • 2 Cranney A, Wells G, Willan A , et al; Osteoporosis Methodology Group and The Osteoporosis Research Advisory Group. Meta-analyses of therapies for postmenopausal osteoporosis. II. Meta-analysis of alendronate for the treatment of postmenopausal women. Endocr Rev 2002; 23 (4) 508-516
  • 3 Cranney A, Tugwell P, Adachi J , et al; Osteoporosis Methodology Group and The Osteoporosis Research Advisory Group. Meta-analyses of therapies for postmenopausal osteoporosis. III. Meta-analysis of risedronate for the treatment of postmenopausal osteoporosis. Endocr Rev 2002; 23 (4) 517-523
  • 4 Siris ES, Pasquale MK, Wang Y, Watts NB. Estimating bisphosphonate use and fracture reduction among US women aged 45 years and older, 2001–2008. J Bone Miner Res 2011; 26 (1) 3-11
  • 5 Girgis CM, Seibel MJ. Atypical femur fractures: a review of the evidence and its implication to clinical practice. Ther Adv Musculoskelet Dis 2011; 3 (6) 301-314
  • 6 Shane E, Burr D, Ebeling PR , et al; 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; 25 (11) 2267-2294
  • 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; 90 (3) 1294-1301
  • 8 Lenart BA, Lorich DG, Lane JM. Atypical fractures of the femoral diaphysis in postmenopausal women taking alendronate. N Engl J Med 2008; 358 (12) 1304-1306
  • 9 Girgis CM, Sher D, Seibel MJ. Atypical femoral fractures and bisphosphonate use. N Engl J Med 2010; 362 (19) 1848-1849
  • 10 Schilcher J, Koeppen V, Aspenberg P, Michaëlsson K. Risk of atypical femoral fracture during and after bisphosphonate use. Acta Orthop 2015; 86 (1) 100-107
  • 11 Khow KSF, Yong TY. Atypical femoral fracture in a patient treated with denosumab. J Bone Miner Metab 2015; 33 (3) 355-358
  • 12 Melendez LM, Llorente I, Garcia E, Garcia-Vicuna R, Castaneda Sanz S. SAT0288 Atypical femoral fractures after treatment with bisphosphonates and denosumab in inflammatory and senile osteoporosis. Poster presentation. Ann Rheum Dis 2015; 74: 762-763
  • 13 Aspenberg P. Denosumab and atypical femoral fractures. Acta Orthop 2014; 85 (1) 1
  • 14 Lo JC, Hui RL, Grimsrud CD , et al. The association of race/ethnicity and risk of atypical femur fracture among older women receiving oral bisphosphonate therapy. Bone 2016; 85: 142-147
  • 15 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; 24 (6) 1095-1102
  • 16 Lee P, van der Wall H, Seibel MJ. Looking beyond low bone mineral density: multiple insufficiency fractures in a woman with post-menopausal osteoporosis on alendronate therapy. J Endocrinol Invest 2007; 30 (7) 590-597
  • 17 Somford MP, Draijer F, Thomassen BJ, Chavassieux PM, Boivin G, Papapoulos SE. Bilateral fractures of the femoral 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; 24 (10) 1736-1740
  • 18 Rizzoli R, Akesson K, Bouxsein M , et al. 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; 22 (2) 373-390
  • 19 Porrino Jr JA, Kohl CA, Taljanovic M, Rogers LF. Diagnosis of proximal femoral insufficiency fractures in patients receiving bisphosphonate therapy. AJR Am J Roentgenol 2010; 194 (4) 1061-1064
  • 20 Chesnut IV CH, Chesnut III CH. Can PET-CT imaging and radiokinetic analyses provide useful clinical information on atypical femoral shaft fracture in osteoporotic patients?. Curr Osteoporos Rep 2012; 10 (1) 42-47
  • 21 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; 468 (12) 3393-3398
  • 22 Chiang CY, Zebaze RM, Ghasem-Zadeh A, Iuliano-Burns S, Hardidge A, Seeman E. Teriparatide improves bone quality and healing of atypical femoral fractures associated with bisphosphonate therapy. Bone 2013; 52 (1) 360-365