Objective.-To evaluate the effect of treatment with alendronate sodium, a potent aminobisphosphonate, on the incidence of nonvertebral fractures in post-menopausal women with osteoporosis. Data Sources.-Published data and data on file at Merck Research Laboratories. Study Selection.-All completed prospective, randomized, placebo-controlled alendronate trials of at least 2 years' duration (5 studies). Data Extraction.-All subjects were women with osteoporosis between the ages of 42 and 85 years, postmenopausal at least 4 years, with lumbar spine bone mineral density (measured using dual-energy x- ray absorptiometry) at least 2.0 SD below the mean for young adult women. All women randomized to treatment with placebo or alendronate at a dose higher than 1 mg per day for at least 2 years were included. Data Synthesis.-In the placebo group (n=590), 60 women reported nonvertebral fractures during 1347 patient-years at risk (overall rate, 4.45 women with fractures per 100 patient-years at risk). In the alendronate group (n = 1012), 73 women reported nonvertebral fractures during 2240 patient-years-at risk (overall rate, 3.26 women with fractures per 100 patient-years at risk). The estimated cumulative incidence of nonvertebral fractures after 3 years was 12.6% in the placebo group and 9.0% in alendronate group. The relative risk for nonvertebral fracture estimated using the Cox proportional hazards model was 0.71 (95% confidence interval, 0.502-0.997) (P=.048). A reduction in risk was consistent across each of the studies and at each major site of osteoporotic fracture, including the hip and wrist. Conclusion.-In postmenopausal women with osteoporosis, treatment with alendronate reduces the risk of nonvertebral fractures over at least 3 years.