Effect of Alendronate on Risk of Fracture in Women With Low Bone Density but Without Vertebral Fractures<SUBTITLE>Results From the Fracture Intervention Trial</SUBTITLE>

TLDR

Alendronate sodium is known to reduce fracture risk in postmenopausal women with vertebral fractures, but its effect in women without vertebral fractures had not been examined. The study aimed to determine whether four years of alendronate would lower the risk of clinical and vertebral fractures in postmenopausal women with low bone mineral density but no vertebral fractures. A randomized, double‑blind, placebo‑controlled trial enrolled 4,432 women aged 54–81 with femoral neck BMD ≤0.68 g/cm², giving 5 mg/day alendronate for two years followed by 10 mg/day, with calcium and vitamin D supplementation, and followed them for an average of 4.2 years to assess fractures and BMD. Alendronate increased BMD at all sites, reduced vertebral fracture risk by 44%, and lowered clinical fracture incidence by 36% in women with osteoporosis (but not in those with higher BMD), without raising adverse events.

Abstract

Context.—Alendronate sodium reduces fracture risk in postmenopausal women who 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 decrease the risk of clinical and vertebral fractures in women who have low bone mineral 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/cm2 or less (Hologic Inc, Waltham, Mass) but no vertebral fracture; 4432 were randomized to alendronate or placebo and 4272 (96%) completed outcome measurements at the final visit (an average of 4.2 years later).Intervention.—All participants reporting calcium intakes of 1000 mg/d or less received a supplement containing 500 mg of calcium and 250 IU of cholecalciferol. Subjects were randomly assigned to either placebo or 5 mg/d of alendronate sodium for 2 years followed by 10 mg/d for the remainder of the trial.Main Outcome Measures.—Clinical fractures confirmed by x-ray reports, new vertebral 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 reduced clinical fractures from 312 in the placebo group to 272 in the intervention 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; treatment-control difference, 6.5%; number needed to treat [NNT], 15), but there 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 fractures by 44% overall (relative risk, 0.56; 95% CI, 0.39-0.80; treatment-control 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 vertebral deformity. Alendronate significantly reduced the risk of clinical fractures among women with osteoporosis but not among women with higher BMD.