Skip to main content

Advertisement

SpringerLink
Log in

Atypical Femur Fractures: A Review

  • Orthopedic Management of Fractures (D Little and T Miclau, Section Editors)
  • Published:
Current Osteoporosis Reports Aims and scope Submit manuscript

Abstract

Bisphosphonates are one of the most commonly prescribed medications for the treatment of osteoporosis. Their use has greatly decreased the number of osteoporosis-related vertebral and nonvertebral fractures. Recently, however, a relationship between long-term bisphosphonate use and subtrochanteric and femoral shaft fractures has been elucidated. These low-energy fractures, termed atypical femur fractures, exhibit unique characteristics in their pathophysiology, presentation, and radiographic appearance compared with more traditional high-energy femur fractures. Here we provide a review based on the most recent literature of the pathophysiology, presentation, evaluation, and management of these fractures. Despite an abundance of literature, atypical femur fractures remain difficult to treat, and surgeons must be aware of the tricks and complications associated with their management.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Kanis JA. Assessment of Osteoporosis at the Primary Health-Care Level, WHO Technical Report. Sheffield, UK:WHO Scientific Group, World Health Organization Collaborating Centre for Metabolic Bone Diseases, University of Sheffield; 2007.

  2. Nieves JW, Cosman F. Atypical subtrochanteric and femoral shaft fractures and possible association with bisphosphonates. Curr Osteoporos Rep. 2010;8:34–9.

    Article  PubMed  Google Scholar 

  3. Poor G, Atkinson EJ, O’Fallon WM, Melton LJ. Determinants of reduced survival following hip fractures in men. Clin Orthop Relat Res. 1995;319:260–5.

    PubMed  Google Scholar 

  4. Melton III LJ. Adverse outcomes of osteoporotic fractures in the general population. J Bone Min Res. 2003;18:1139–41.

    Article  Google Scholar 

  5. Dell R, Greene D. Is osteoporosis diseases management cost effective? Curr Osteoporos Rep. 2010;8:49–55.

    Article  PubMed  Google Scholar 

  6. Cummings SR, Melton LJ. Epidemiology and outcomes of osteoporotic fractures. Lancet. 2002;359:1761–7.

    Article  PubMed  Google Scholar 

  7. Black DM, Delmas PD, Eastell R, Reid IR, Boonen S, Cauley JA, et al. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med. 2007;356:1809–22.

    Article  PubMed  CAS  Google Scholar 

  8. Unnanuntana A, Saleh A, Mensah KA, Kleimeyer JP, Lane JM. Atypical femoral fractures: what do we know about them? AAOS Exhibit Selection. J Bone Joint Surg Am. 2013;95:e8 1–13.

    Article  Google Scholar 

  9. De Das S, Setiobudi T, Shen L. A rational approach to management of alendronate-related subtrochanteric fractures. J Bone Joint Surg (Br). 2010;92:679–86.

    Article  Google Scholar 

  10. Girgis CM, Seibel MJ. Guilt by association? Examining the role of bisphosphonate therapy in the development of atypical femur fractures. Bone. 2011;48:963–5.

    Article  PubMed  CAS  Google Scholar 

  11. 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;24:1736–40.

    Article  PubMed  Google Scholar 

  12. Odvina CV, Zerwekh JE, Rao DS, et al. Severely suppressed bone turnover: a potential complication of alendronate therapy. J Clin Endocrinol Metab. 2005;90:1294–301.

    Article  PubMed  CAS  Google Scholar 

  13. Capeci CM, Tejwani NC. Bilateral low-energy simultaneous or sequential femoral fractures in patients on long-term alendronate therapy. J Bone Joint Surg Am. 2009;91:2556–61.

    Article  PubMed  Google Scholar 

  14. Hollick RJ, Reid DM. Role of bisphosphonates in the management of postmenopausal osteoporosis: an update on recent safety anxieties. Menopaus Int. 2011;17:66–72.

    Google Scholar 

  15. Neviaser AS, Lane JM, Lenart BA, Edobor-Osula F, Lorich DG. Low-energy femoral shaft fractures associated with alendronate use. J Orthop Trauma. 2008;22:346–50.

    Article  PubMed  Google Scholar 

  16. Yoon RS, Hwang JS, Beebe KS. Long-term bisphosphonate usage and subtrochanteric insufficiency fractures: a cause for concern? J Bone Joint Surg (Br). 2011;93:1289–95.

    Article  CAS  Google Scholar 

  17. Shane E, Burr D, Ebeling PR, Abrahamsen B, Adler RA, Brown TD, 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):2267–94.

    Article  PubMed  Google Scholar 

  18. Shane E, Burr D, Abrahamsen B, Adler R, Brown T, Cheung A, 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):1–23. Reviews the latest evidence related to the epidemiology, pathogenesis, and medical management of atypical femur fractures, as well as sets an updated, accepted definition.

    Article  PubMed  Google Scholar 

  19. Compston J. Pathophysiology of atypical femoral fractures and osteonecrosis of the jaw. Osteoporos Int. 2011;22:2951–61.

    Article  PubMed  CAS  Google Scholar 

  20. Watts N, Diab D. Long-term use of bisphosphonates in osteoporosis. J Clin Endocrinol Metab. 2010;95:1555–65.

    Article  PubMed  CAS  Google Scholar 

  21. 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;15:613–20.

    Article  PubMed  CAS  Google Scholar 

  22. Visekruna M, Wilson D, McKiernan FE. Severely suppressed bone turnover and atypical skeletal fragility. J Clin Endocrinol Metab. 2008;93:2948–52.

    Article  PubMed  CAS  Google Scholar 

  23. Armamento-Villareal R, Napoli N, Diemer K, Watkins M, Civitelli R, Teitelbaum S, et al. Bone turnover in bone biopsies of patients with low-energy cortical fractures receiving bisphosphonates: a case series. Calcif Tissue Int. 2009;85:37–44.

    Article  PubMed  CAS  Google Scholar 

  24. Wang Z, Bhattacharyya T. Trends in the incident of subtrochanteric fragility fractures and bisphosphonate use among the US elderly. J Bone Miner Res. 2011;26:553–60.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  25. Park-Wyllie LY, Mamdani MM, Juurlink DN, et al. Bisphosphonate use and risk of subtrochanteric or femoral shaft fractures in older women. JAMA. 2011;305:783–9. This is a case-control study that demonstrates the association between prolonged bisphosphonate use and the increased risk of atypical femur fractures.

    Article  PubMed  CAS  Google Scholar 

  26. Schilcher J, Michaelson K, Aspenberg P. Bisphosphonate use and atypical fractures of the femoral shaft. N Engl J Med. 2011;364:1728–37.

    Article  PubMed  CAS  Google Scholar 

  27. Giusti A, Hamdy NA, Dekkers OM, Ramautar SR, Dijkstra S, Papapoulos SE. Atypical fractures and bisphosphonate therapy: a cohort study of patients with femoral fracture with radiographic adjudication of fracture site and features. Bone. 2011;48(5):966–71.

    Article  PubMed  CAS  Google Scholar 

  28. Marcano A, Taormina D, Egol KA, Peck V, Tejwani NC. Are race and sex associated with the occurrence of atypical femoral fractures? Clin Orthop Relat Res. 2014;472(3):1020–7. Review of prospectively collected demographic data demonstrating the increased risk of woman, Asians and Hispanics for suffering an atypical femur fracture in the setting of bisphosphonate use.

    Article  PubMed  Google Scholar 

  29. Beaudouin-Bazire C, Dalmas N, Bourgeois J, Babinet A, Anract P, Chantelot C, et al. Real frequency of ordinary and atypical sub-trochanteric and diaphyseal fractures in France based on X-rays and medical file analysis. Joint Bone Spine. 2013;80(2):201–5.

    Article  PubMed  Google Scholar 

  30. Dell RM, Adams AL, Greene DF, Funahashi TT, Silverman SL, Eisemon EO, et al. Incidence of atypical nontraumatic diaphyseal fractures of the femur. J Bone Miner Res. 2012;27(12):2544–50.

    Article  PubMed  Google Scholar 

  31. Lo JC, Huang SY, Lee GA, Khandewal S, Provus J, Ettinger B, et al. Clinical correlates of atypical femoral fracture. Bone. 2012;51(1):181–4.

    Article  PubMed  Google Scholar 

  32. Giusti A, Hamdy NA, Papapoulos SE. Atypical fractures of the femur and bisphosphonate therapy: a systematic review of case/case series studies. Bone. 2010;47(2):169–80.

    Article  PubMed  CAS  Google Scholar 

  33. Wang K, Moaveni A, Dowrick A, et al. Alendronate-associated femoral insufficiency fractures and femoral stress reactions. J Orthop Surg. 2011;19(1):89–92.

    Google Scholar 

  34. Kwek EB, Goh SK, Koh JS, Png MA, Howe TS. An emerging pattern of sub- trochanteric stress fractures: a long-term complication of alendronate therapy? Injury. 2008;39:224–31.

    Article  PubMed  Google Scholar 

  35. Clement DB, Ammann W, Taunton JE, et al. Exercise-induced stress injuries to the femur. Int J Sports Med. 1993;14:347–52.

    Article  PubMed  CAS  Google Scholar 

  36. Haworth AE, Webb J. Skeletal complications of bisphosphonate use: what the radiologist should know. Br J Radiol. 2012;85:1333–42.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  37. Chan SS, Rosenberg ZS, Chan K, et al. Subtrochanteric femoral fractures in patients receiving long-term alendronate therapy: imaging features. Am J Roentgenol. 2010;194:1581–6.

    Article  Google Scholar 

  38. Perret MC, Foulner D, Glennon DA. Subtrochanteric fractures in patients on long term bisphosphonate therapy. J Surg Radiol. 2011;2:294–302.

    Google Scholar 

  39. Aghbari MS, Honig S, Egol KA. Diagnosis and treatment of bisphosphonate-induced atypical femoral fractures. Aging Health. 2013;9(4):451–7.

    Article  Google Scholar 

  40. Grey A, Bolland M, Horne A, Gamble G, Reid IR. Prolonged antiresorptive activity of zolendronate: a randomized, controlled trial. J Bone Miner Res. 2010;25(10):2251–5.

    Article  PubMed  CAS  Google Scholar 

  41. Porras AG, Holland SD, Gertz BJ. Pharmacokinetics of Alendronate. Clin Pharmacokinet. 1999;36(5):315–28.

    Article  PubMed  CAS  Google Scholar 

  42. Markman LH, Allison MB, Rosenberg ZS, Vieira RL, Babb JS, Tejwani NC, 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;21:1–23.

    Google Scholar 

  43. Gehrig L, Lane J, O’Connor MI. Osteoporosis: management and treatment strategies for orthopaedic surgeons. J Bone Joint Surg Am. 2008;90(6):1362–74.

    PubMed  Google Scholar 

  44. Ross CA, Taylor CL, Yaktine AL, Del Valle HB. Dietary reference intakes for Calcium and Vitamin D. Washington, DC: National Academies Press; 2011. p. 1132.

    Google Scholar 

  45. Alcantara-Martos T, Delgado-Martinez AD, Vega MV, Carrscal MT, Munuera-Martinez L. Effect of vitamin C on fracture healing in elderly Osteogenic Disorder Shionogi rats. J Bone Joint Surg (Br). 2007;89(3):402–7.

    Article  CAS  Google Scholar 

  46. Sarisozen B, Durak K, Dincer G, Bilgen OF. The effects of vitamins E and C on fracture healing in rats. J Int Med Res. 2002;30(3):309–13.

    Article  PubMed  CAS  Google Scholar 

  47. Andreassen TT, Fledelius C, Ejersted C, Oxlund H. Increases in callus formation and mechanical strength of healing fractures in old rats treated with parathyroid hormone. Acta Orthop Scand. 2001;72(3):304–7.

    Article  PubMed  CAS  Google Scholar 

  48. Andreassen TT, Ejersted C, Oxlund H. Intermittent parathyroid hormone (1-34) treatment increases callus formation and mechanical strength of healing rat fractures. J Bone Miner Res. 1999;14(6):960–8.

    Article  PubMed  CAS  Google Scholar 

  49. Skripitz R, Andreassen TT, Aspenberg P. Parathyroid hormone (1-34) increases the density of rat cancellous bone in a bone chamber. A dose-response study. J Bone Joint Surg (Br). 2000;82(1):138–41.

    Article  CAS  Google Scholar 

  50. Zanchetta JR, Bogado CE, Ferretti JL, Wang O, Wilson MG, Sato M, et al. Effects of teriparatide [recombinant human parathyroid hormone (1-34)] on cortical bone in postmenopausal women with osteoporosis. J Bone Miner Res. 2003;18(3):539–43.

    Article  PubMed  CAS  Google Scholar 

  51. Aspenberg P, Johansson T. Teriparatide improves early callus formation in distal radial fractures. Acta Orthop. 2010;81(2):234–6.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Peichl P, Holzer LA, Maier R, Holzer G. Parathyroid hormone 1-84 accelerates fracture-healing in pubic bones of elderly osteoporotic women. J Bone Joint Surg Am. 2011;93(17):1583–7.

    Article  PubMed  Google Scholar 

  53. Aspenberg P, Genant HK, Johansson T, Nino AJ, See K, Krohn K, et al. Teriparatide for acceleration of fracture repair in humans: a prospective, randomized, double‐blind study of 102 postmenopausal women with distal radial fractures. J Bone Miner Res. 2010;25:404–14.

    Article  PubMed  CAS  Google Scholar 

  54. Mastaglia S, Aguilar G, Rossi E. Rapid resolution with teriparatide in delayed healing of atypical fracture associated to long‐term bisphosphonate use. J Bone Miner Res. 2012;27(Suppl 1): S1. Available from: http://www.asbmr.org/Meetings/AnnualMeeting/AbstractDetail.aspx?aid46ec07ad-15ae-4b15-ab81-a56304568df5.

  55. Bock O, Felsenberg D. Atypical subtrochanteric and diaphyseal femoral fractures associated with long‐term bisphosphonate use in postmenopausal osteoporosis—a case study. J Bone Miner Res. 2012;27(Suppl 1): S1. Available from: http://www.asbmr.org/Meetings/AnnualMeeting/AbstractDetail.aspx?aid¼db68cca9‐61f6‐46bb‐93ae‐091ce04896e2.

  56. Cheung AM, Bleakney R, Kahn A, et al. Effect of teriparatide on fracture healing in patients with non‐displaced incomplete atypical femur fractures. J Bone Miner Res. 2012;27(Suppl 1): S1. Available from: http://www.asbmr.org/Meetings/AnnualMeeting/AbstractDetail.aspx?aid¼60a3d5a5‐35f7‐4288‐8ab5‐08e498e11594.

  57. Miller PD, McCarthy E. Quantitative bone histomorphometry in patients with bisphosphonate‐associated atypical subtrochanteric femur fractures before and after 12 months of teriparatide. J Bone Miner Res. 2012;12(Suppl 1): S1. Available from: http://www.asbmr.org/Meetings/AnnualMeeting/AbstractDetail.aspx?aid¼6fcb5c2a‐81ce‐4f93‐a919‐5dfba3b97530.

  58. Chiang CY, Zebaze RM, Ghasem-Zadeh A, Luliano-Burns S, Hardidge A, Seeman E. Teriparatide improves bone quality and healing of atypical femoral fractures associated with bisphosphonate therapy. Bone. 2013;52:360–5.

    Article  PubMed  CAS  Google Scholar 

  59. Lin EA, Liu CJ, Monroy A, Khurana S, Egol KA. Prevention of atrophic nonunion by the systemic administration of parathyroid hormone (PTH 1-34) in an experimental animal model. J Orthop Trauma. 2012;26(12):719–23.

    Article  PubMed  Google Scholar 

  60. Banffy MB, Vrahas MS, Ready JE, Abraham JA. Nonoperative versus prophylactic treatment of bisphosphonate-associated femoral stress fractures. Clin Orthop Relat Res. 2011;469:2028–34. This is a retrospective review of patients with atypical femur fractures comparing nonoperative management with prophylactic operative fixation. The study demonstrates a high rate of fracture completion and displacement with nonoperative treatment.

    Article  PubMed  PubMed Central  Google Scholar 

  61. 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):3393–8.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Egol KA, Park JH, Prensky C, Rosenberg ZS, Peck V, Tejwani NC. Surgical treatment improves clinical and functional outcomes for patients who sustain incomplete bisphosphonate-related femur fractures. J Orthop Trauma. 2013;27:331–5. This is a retrospective review that compares nonoperative and operative management of incomplete atypical femur fractures. The results indicate faster healing and improved pain scores in patients treated operatively.

    Article  PubMed  Google Scholar 

  63. Prasarn ML, Ahn J, Helfet DL, Lane JM, Lorich DG. Bisphosphonate-associated femur fractures have high complication rates with operative fixation. Clin Orthop Relat Res. 2012;470:2295–301.

    Article  PubMed  PubMed Central  Google Scholar 

  64. Cao Y, Mori S, Mashiba T, Westmore MS, Ma L, Sato M, et al. Raloxifene, estrogen, and alendronate affect the processes of fracture repair differently in ovariectomized rats. J Bone Miner Res. 2002;17(12):2237–46.

    Article  PubMed  CAS  Google Scholar 

  65. Desai PA, Vyas PA, Lane JM. Atypical femoral fractures: a review of the literature. Curr Osteoporos Rep. 2013;11:179–87.

    Article  PubMed  Google Scholar 

  66. 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;71(1):186–90.

    Article  PubMed  CAS  Google Scholar 

Download references

Compliance with Ethics Guidelines

Conflict of Interest

W. H. Bronson, I. D. Kaye, and K. A. Egol declare that they have no conflicts of interest.

Human and Animal Rights and Informed Consent

All studies by K. A. Egol involving animal and/or human subjects were performed after approval by the appropriate institutional review boards. When required, written informed consent was obtained from all participants.

Author information

Authors and Affiliations

  1. Department of Orthopaedic Surgery, NYU Hospital for Joint Diseases, 301 E 17th St, New York, NY, USA

    Wesley H. Bronson, I. David Kaye & Kenneth A. Egol

Authors
  1. Wesley H. Bronson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. I. David Kaye
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kenneth A. Egol
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kenneth A. Egol.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bronson, W.H., Kaye, I.D. & Egol, K.A. Atypical Femur Fractures: A Review. Curr Osteoporos Rep 12, 446–453 (2014). https://doi.org/10.1007/s11914-014-0239-7

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11914-014-0239-7

Keywords

Search

Navigation