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
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
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
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
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.