Subtrochanteric and Diaphyseal Femur Fractures in Patients Treated With Alendronate: A Register-Based National Cohort Study


  • Dr. Abrahamsen receives consultancy fees from Nycomed and Novartis, research grants from Roche, and speaker's fees from Servier, Eli Lilly, and MSD. Dr. Eiken receives speaker fees from Nycomed, Roche, and Servier. Dr. Eastell receives research funding or consultation honoraria from Amgen, AstraZeneca, Aventis, Eli Lilly, GlaxoSmithKline, Hologic, Interleukin Genetics, Kyphon, Lilly, Maxygen, Nastech Pharmaceuticals, Nestle Research Center, New Zealand Milk Limited, Novartis, Novo-Nordisk, Ono Pharma, Organon, Osteologix, Paraxel, Pfizer, Procter & Gamble, Roche Diagnostics, Sanofi-aventis, Servier, Shire, Transpharma Medical Limited, Unilever, and Unipath.

  • Published online on December 29, 2009


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.