Risk of atypical femoral fracture during and after bisphosphonate use

Acta Orthop. 2015 Feb;86(1):100-7. doi: 10.3109/17453674.2015.1004149. Epub 2015 Jan 13.


Background and purpose: Use of bisphosphonates in women is associated with higher risk of atypical femoral fractures. The risk in terms of timing of use and type of bisphosphonate, and in men, remains unclear.

Patients and methods: We reviewed radiographs of 5,342 Swedish women and men aged 55 years or more who had had a fracture of the femoral shaft in the 3-year period 2008-2010 (97% of those eligible), and found 172 patients with atypical fractures (93% of them women). We obtained data on medication and comorbidity. The risk of atypical fracture associated with bisphosphonate use was estimated in a nationwide cohort analysis. In addition, we performed a case-control analysis with comparison to 952 patients with ordinary shaft fractures. A short report of the findings has recently been presented (Schilcher et al. 2014a). Here we provide full details.

Results: The age-adjusted relative risk (RR) of atypical fracture associated with bisphosphonate use was 55 (95% CI: 39-79) in women and 54 (CI: 15-192) in men. In bisphosphonate users, women had a 3-fold higher risk than men (RR = 3.1, CI: 1.1-8.4). Alendronate users had higher risk than risedronate users (RR = 1.9, CI: 1.1-3.3). The RR after 4 years or more of use reached 126 (CI: 55-288), with a corresponding absolute risk of 11 (CI: 7-14) fractures per 10,000 person-years of use. The risk decreased by 70% per year since last use.

Interpretation: Women have a higher risk of atypical femoral fracture than men. The type of bisphosphonate used may affect risk estimates and the risk decreases rapidly after cessation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alendronate / therapeutic use*
  • Bone Density Conservation Agents / therapeutic use*
  • Case-Control Studies
  • Cohort Studies
  • Diphosphonates / therapeutic use*
  • Etidronic Acid / analogs & derivatives*
  • Etidronic Acid / therapeutic use
  • Female
  • Femoral Fractures / diagnostic imaging
  • Femoral Fractures / epidemiology*
  • Humans
  • Male
  • Middle Aged
  • Osteoporotic Fractures / prevention & control*
  • Radiography
  • Retrospective Studies
  • Risedronic Acid
  • Risk Factors
  • Sex Factors
  • Sweden / epidemiology
  • Time Factors


  • Bone Density Conservation Agents
  • Diphosphonates
  • Risedronic Acid
  • Etidronic Acid
  • Alendronate