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

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.