Subtrochanteric and diaphyseal femur fractures in patients treated with alendronate: a register-based national cohort study

J Bone Miner Res. 2009 Jun;24(6):1095-102. doi: 10.1359/jbmr.081247.


Alendronate (aln) is a potent bisphosphonate with a prolonged duration of action. Recent reports have found long-term aln use to be common in patients with subtrochanteric or proximal diaphyseal femur fracture, raising concerns that these fractures could be a consequence of excessive suppression of bone turnover. Two national observational register-based studies were performed: (1) cross-sectional study (N = 11,944) comparing age distribution, exposure, and trauma mechanisms between different types of proximal femur fractures and (2) matched cohort study in patients with prior nonhip fractures (N = 5187 + 10,374), testing the hypothesis that the increase in the risk of subsequent atypical femur fractures exceeded the increase in typical hip fractures. We also sought evidence of a dose-response relationship, where high adherence to or long-term use of aln led to more atypical femur fractures. We found that 7% of patients with atypical fractures were aln exposed, and the same was found for typical hip fractures. In the cohort study, the HR for subtrochanteric/diaphyseal fracture with aln was 1.46 (0.91-2.35, p = 0.12) compared with 1.45 (1.21-1.74, p < 0.001) for hip fracture after adjustment for comorbidity and co-medications. The risk was reduced by high adherence, and the ratio between hip and subtrochanteric/diaphyseal femur fractures was identical in aln-treated patients and the control cohort even in the limited number of patients who received long-term treatment. Subtrochanteric/diaphyseal femur fractures share the epidemiology and treatment response of classical hip fractures and are best classified as osteoporotic fractures.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alendronate / therapeutic use*
  • Cohort Studies
  • Cross-Sectional Studies
  • Denmark / epidemiology
  • Etidronic Acid / therapeutic use
  • Female
  • Femoral Fractures / epidemiology
  • Femoral Fractures / prevention & control*
  • Humans
  • Incidence
  • Male
  • Patient Compliance
  • Registries*


  • Etidronic Acid
  • Alendronate