title: Subtrochanteric and diaphyseal femur fractures in patients treated with alendronate: a register-based national cohort study.
abstract: 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.
authors.affiliation: Department of Medicine and Endocrinology F, Copenhagen University Hospital Gentofte, Hellerup, Denmark. b.abrahamsen@physician.dk
authors.forename: Bo
authors.initials: B
authors.lastname: Abrahamsen
authors.forename: Pia
authors.initials: P
authors.lastname: Eiken
authors.forename: Richard
authors.initials: R
authors.lastname: Eastell
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D019386:Alendronate / Q000627:therapeutic use*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D003718:Denmark / Q000453:epidemiology; D012968:Etidronic Acid / Q000627:therapeutic use; D005260:Female; D005264:Femoral Fractures / Q000453:epidemiology / Q000517:prevention & control*; D006801:Humans; D015994:Incidence; D008297:Male; D010349:Patient Compliance; D012042:Registries
chemical_list: D012968:Etidronic Acid; D019386:Alendronate