Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures - Results from the fracture intervention trial

Context.-Alendronate sodium reduces fracture risk in postmenopausal women w ho have vertebral fractures, but its effects on fracture risk have not been studied for women without vertebral fractures. Objective.-To test the hypothesis that 4 years of alendronate would decreas e the risk of clinical and vertebral fractures in women who have low bone m ineral density (BMD) but no vertebral fractures. Design.-Randomized, blinded, placebo-controlled trial. Setting.-Eleven community-based clinical research centers. Subjects.-Women aged 54 to 81 years with a femoral neck BMD of 0.68 g/cm(2) or less (Hologic Inc, Waltham, Mass) but no vertebral fracture; 4432 were randomized to alendronate or placebo and 4272 (96%) completed outcome measu rements at the final visit (an average of 4.2 years later). Intervention.-All participants reporting calcium intakes of 1000 mg/d or le ss received a supplement containing 500 mg of calcium and 250 IU of choleca lciferol. Subjects were randomly assigned to either placebo or 5 mg/d of al endronate sodium for 2 years followed by 10 mg/d for the remainder of the t rial. Main Outcome Measures.-Clinical fractures confirmed by x-ray reports, new v ertebral deformities detected by morphometric measurements on radiographs, and BMD measured by dual x-ray absorptiometry. Results.-Alendronate increased BMD at all sites studied (P<.001) and reduce d clinical fractures from 312 in the placebo group to 272 in the interventi on group, but not significantly so (14% reduction; relative hazard [RH], 0. 86; 95% confidence interval [CI], 0.73-1.01). Alendronate reduced clinical fractures by 36% in women with baseline osteoporosis at the femoral neck (> 2.5 SDs below the normal young adult mean; RH, 0.64; 95% CI, 0.50-0.82; tre atment-control difference, 6.5%; number needed to treat [NNT], 15), but the re was no significant reduction among those with higher BMD (RH, 1.08; 95% CI, 0.87-1.35). Alendronate decreased the risk of radiographic vertebral fr actures by 44% overall (relative risk, 0.56; 95% CI, 0.39-0.80; treatment-c ontrol difference, 1.7%; NNT, 60). Alendronate did not increase the risk of gastrointestinal or other adverse effects. Conclusions.-In women with low BMD but without vertebral fractures, 4 years of alendronate safely increased BMD and decreased the risk of first verteb ral deformity. Alendronate significantly reduced the risk of clinical fract ures among women with osteoporosis but not among women with higher BMD.