The antifracture efficacy of alendronate.

Two multicentre, double-blind, randomised trials were performed involving 994 postmenopausal women (mean age 64 yr, range 45-80 yr) with osteoporosis and using identical protocols at centres in the USA and internationally. Patients were included if bone density was +/- 2.5 standard deviations below the young-normal mean. The presence of fracture was not an inclusion criterion. Patients received placebo or alendronate (ALN) (5 or 10 mg/day for 3 yr, or 20 mg/day for 2 yr, then 5 mg/day for 1 yr). All received 500 mg elemental calcium. Analysis of vertebral fracture rates was based on preplanned pooling of all treatment groups. Analysis of nonvertebral fracture rates was based on preplanned pooling of this protocol and 3 similar studies in postmenopausal women with osteoporosis. Bone density decreased in the patients receiving placebo and increased in the patients receiving ALN. The optimum dose to increase bone density was 10 mg daily. After 3 years, bone density was 8.8 +/- 0.4% (lumbar spine), 5.9 +/- 0.5% (femoral neck) and 7.8 +/- 0.6 (trochanter) higher in the patients treated with 10 mg/day ALN than in patients receiving placebo. One or more new vertebral fractures occurred in 17 of 526 patients receiving ALN (3.2%) and 22 of 355 patients receiving placebo (6.2%) (a 48% reduction, (P = 0.034). Of the patients having new vertebral fractures, > or = 2 fractures occurred in 3 of 17 (18%) ALN-treated patients and 15 of 22 (68%) receiving placebo (P < 0.001). Fewer patients receiving ALN had vertebral fractures whether stratified by age or by the presence or absence of vertebral fractures at entry. Among patients sustaining vertebral fractures, height loss was 23.3 mm in patients receiving placebo and 5.9 mm in patients receiving ALN. Clinical adverse events, mainly upper gastrointestinal irritation, resulted in discontinuations in 6% (placebo), 5.4% (5 mg), 4.1% (10 mg), 8% (20 mg/5 mg). In the pooled analysis across all 5 osteoporosis treatment clinical trials, nonvertebral fractures occurred in 73 of 1012 ALN-treated women (76 fractures in 2240 patient-years) and in 60 of 590 women receiving placebo (70 fractures in 1347 patient-years). After 3 years, the cumulative incidences (ALN vs placebo) were 9% and 12.6%, a 29% reduction in absolute risk compared with placebo (P = 0.048). Alendronate is a well-tolerated new treatment that reduces the risk and severity of new vertebral fractures, reduces height loss and may reduce the risk of nonvertebral fractures.