Background:​ Previous studies have shown that alendronate can increase bone mineral density (BMD) and prevent radiographically defined (morphometric) vertebral fractures. The Fracture Intervention Trial aimed to investigate the effect of alendronate on the risk of morphometric as well as clinically evident fractures in postmenopausal women with low bone mass.

Methods:​ Women aged 55–81 with low femoral-neck BMD were enrolled in two study groups based on presence or absence of an existing vertebral fracture. Results for women with at least one vertebral fracture at baseline are reported here. 2027 women were randomly assigned placebo (1005) or alendronate (1022) and followed up for 36 months. The dose of alendronate (initially 5 mg daily) was increased (to 10 mg daily) at 24 months, with maintenance of the double blind. Lateral spine radiography was done at baseline and at 24 and 36 months. New vertebral fractures, the primary endpoint, were defined by morphometry as a decrease of 20% (and at least 4 mm) in at least one vertebral height between the baseline and latest follow-up radiograph. Non-spine clinical fractures were confirmed by radiographic reports. New symptomatic vertebral fractures were based on self-report and confirmed by radiography.

Findings:​ Follow-up radiographs were obtained for 1946 women (98% of surviving participants). 78 (8·0%) of women in the alendronate group had one or more new morphometric vertebral fractures compared with 145 (15·0%) in the placebo group (relative risk 0·53 [95% CI 0·41–0·68]). For clinically apparent vertebral fractures, the corresponding numbers were 23 (2·3%) alendronate and 50 (5·0%) placebo (relative hazard 0·45 [0·27–0·72]). The risk of any clinical fracture, the main secondary endpoint, was lower in the alendronate than in the placebo group (139 [13·6%] vs 183 [18·2%];​ relative hazard 0·72 [0·58–0·90]). The relative hazards for hip fracture and wrist fracture for alendronate versus placebo were 0·49 (0·23–0·99) and 0·52 (0·31–0·87). There was no significant difference between the groups in numbers of adverse experiences, including upper-gastrointestinal disorders.

Interpretation:​ We conclude that among women with low bone mass and existing vertebral fractures, alendronate is well tolerated and substantially reduces the frequency of morphometric and clinical vertebral fractures, as well as other clinical fractures.