Most of the many randomized trials of bisphosphonates demonstrated a significant improvement in BMD associated with the medication. Therefore, this review focused on trials reporting fracture data. A meta-analysis of five randomized, placebo-controlled trials of alendronate therapy for at least 2 years in postmenopausal women with osteoporosis (82), all of whom had a BMD T score of −2.0 or lower, found that the relative risk for a nonvertebral fracture for the alendronate group relative to placebo was 0.71 (CI, 0.5 to 0.997; P = 0.048). Three additional reports of two alendronate trials not included in the meta-analysis were identified. In one study, the alendronate-treated group achieved statistically significant increases in BMD at multiple sites compared with the placebo group (83). However, no significant difference was found in nonvertebral fractures between the two groups. The Fracture Intervention Trial (84) was a study with two groups; one group contained women with existing vertebral fractures and the other group had women with no history of vertebral fractures. After 2 years of treatment with alendronate or placebo, the alendronate-treated women with prior vertebral fractures experienced a decrease in radiographically apparent vertebral fractures (relative risk, 0.53 [CI, 0.41 to 0.68]) as well as clinically apparent vertebral fractures (relative hazard, 0.45 [CI, 0.27 to 0.72]) relative to the placebo group (84). The treatment group also experienced a decrease in nonvertebral fractures (relative hazard, 0.80 [CI, 0.63 to 1.01]), including hip fractures (relative hazard, 0.49 [CI, 0.23 to 0.99]). After 3 years of treatment, subgroup analyses of the cohort with existing vertebral fractures demonstrated that the 47% risk reduction in new vertebral fractures experienced by the entire cohort was consistent across age groups, baseline BMD, and number of preexisting vertebral fractures (85). To prevent one new vertebral fracture, eight women at least 75 years of age must receive treatment for 5 years. In the second arm of the study (women without a history of vertebral fractures), BMD increased at all sites, but the reduction in fractures was statistically significant only among women with a T score at the femoral neck of −2.5 or lower (86).