Summary: While alendronate inhibits atherosclerosis experimentally, its effect on lower limb ischemia risk is unknown. Our results suggest that alendronate reduces the risk of lower limb ischemic vascular events requiring surgical interventions, including amputation. Our results are relevant for patients at risk of lower limb ischemia undergoing fragility fracture treatment. Introduction: This study aimed to determine the association between alendronate therapy and the risk of lower limb ischemic vascular events (i.e., bypass surgery, endovascular stenting, and major lower limb amputation for lower limb ischemia). Methods: We used a nationwide population-based cohort of patients aged over 50 years diagnosed with a vertebral or hip fracture between January 1999 and June 2010. We compared the risk of lower limb ischemic vascular events between patients undergoing treatment with alendronate (n =3,731) and an age- and sex-matched comparison group (n =7,462) over 5 years of follow-up. Hazard ratios (HR) were estimated using Cox proportional regression analysis with adjustment for treatment status, comorbidities, and other variables. Results: Ten patients (0.3%) in the alendronate treatment group had a lower limb ischemic vascular event compared with 51 patients (0.7%) in the comparison group. The incidence of lower limb ischemic vascular events was 8.4 (95% CI, 4.0-15.5) per 10,000 person-years in the alendronate group and 21.8 (95% CI, 16.2-28.7) per 10,000 person-years in the comparison group. The risk of a lower limb ischemic vascular event in the alendronate treatment group was lower (adjusted HR, 0.41; 95% CI, 0.21-0.82). Conclusion: Alendronate treatment was associated with a reduced risk of lower limb ischemic vascular events among hip or vertebral fragility fracture patients.
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