Increasing occurrence of atypical femoral fractures associated with bisphosphonate use

Arch Intern Med. 2012 Jun 25;172(12):930-6. doi: 10.1001/archinternmed.2012.1796.


Background: Current evidence suggests that there is an association between bisphosphonate therapy and atypical femoral fractures, but the extent of this risk remains unclear.

Methods: Between 1999 and 2010, a total of 477 patients 50 years and older were hospitalized with a subtrochanteric or femoral shaft fracture at a single university medical center. Admission radiographs and medical and treatment records were examined, and patients were classified as having atypical or classic femoral fractures. A random sample of 200 healthy individuals without femoral fracture were also identified. Multivariate logistic regression was used to assess the association of bisphosphonate use and atypical femoral fracture, and the incidence rates of each type of fracture over time were calculated.

Results: Thirty-nine patients with atypical fractures and 438 patients with classic fractures were identified. Of the patients with atypical fractures, 32 (82.1%) had been treated with bisphosphonates compared with 28 (6.4%) in the classic fractures group (odds ratios [OR], 66.9; 95% CI, 27.1-165.1) and 11.5% in the group without fracture (OR, 35.2; 95% CI, 13.9-88.8). Bisphosphonate use was associated with a 47% reduction in risk of classic fracture (OR, 0.5; 95% CI, 0.3-0.9). Considering the duration of use, the ORs (95% CIs) for atypical fractures were 35.1 (10.0-123.6) for less than 2 years, 46.9 (14.2-154.4) for 2 to 5 years, 117.1 (34.2-401.7) for 5 to 9 years, and 175.7 (30.0-1027.6) for more than 9 years compared with no use. A contralateral fracture occurred in 28.2% of atypical cases and in 0.9% of classic cases (OR, 42.6; 95% CI, 12.8-142.4). The incidence rate of atypical fractures was low (32 cases per million person-years) and increased by 10.7% per year on average.

Conclusions: Atypical femoral fractures were associated with bisphosphonate use; longer duration of treatment resulted in augmented risk. The incidence of atypical fractures increased over a 12-year period, but the absolute number of such fractures is very small.

MeSH terms

  • Adrenal Cortex Hormones / therapeutic use
  • Aged
  • Aged, 80 and over
  • Bone Density Conservation Agents / adverse effects*
  • Case-Control Studies
  • Diphosphonates / adverse effects*
  • Female
  • Femoral Fractures / diagnostic imaging*
  • Femoral Fractures / epidemiology*
  • Femoral Fractures / etiology
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Odds Ratio
  • Radiography
  • Risk
  • Sex Factors
  • Time Factors
  • Vitamin D / therapeutic use


  • Adrenal Cortex Hormones
  • Bone Density Conservation Agents
  • Diphosphonates
  • Vitamin D