TREATMENT WITH ALENDRONATE PREVENTS FRACTURES IN WOMEN AT HIGHEST RISK - RESULTS FROM THE FRACTURE INTERVENTION TRIAL

Background: The efficacy of antiresorptive therapy in preventing fract ures in women at highest fracture risk, such as very elderly women or those with severe osteoporosis, is uncertain. Participants and Methods : Using data from a double-blind, randomized, placebo-controlled clini cal trial that enrolled 2027 postmenopausal women aged 55 to 81 years with low femoral neck bone mineral density (BMD) and existing vertebra l fractures, we examined the consistency of the effect of treatment wi th alendronate sodium in preventing fractures within a priori-specifie d risk subgroups defined at baseline by age, bone density, number of p reexisting vertebral fractures, and history of postmenopausal fracture . The women were randomized to oral administration of alendronate or p lacebo and followed up for an average of 2.9 years. The initial dose o f alendronate sodium was 5 mg/d; the dosage was increased from 5 to 10 mg/d at 24 months. New vertebral fractures, the primary end point of this arm of the trial, were defined by morphometry as a decrease of 20 % and at least 4 mm in any vertebral height between baseline and a fol low-up radiograph at 36 months. Incident clinical fractures, the secon dary end point, included non-spine and clinical (symptomatic) vertebra l fractures. All clinical fractures were confirmed with x-ray film rep orts or, in the case of clinical vertebral fractures, x-ray films. Res ults: Overall, there was a 47% significant reduction in risk of new ve rtebral fractures in the alendronate group compared with the placebo g roup. The reduction in risk of new vertebral fracture was consistent a cross fracture risk categories including age (relative risk [RR], 0.49 in women <75 years compared with 0.62 in those greater than or equal to 75 years), BMD (RR, 0.54 in women with a femoral neck BMD <0.59 g/c m(2) [median] compared with 0.53 in those with a BMD greater than or e qual to 0.59 g/cm2), and number of preexisting vertebral fractures (RR , 0.58 in women with 1 vertebral fracture compared with 0.52 in those with greater than or equal to 2). The overall significant 28% reductio n in risk of incident clinical fractures in the alendronate group comp ared with the placebo group was also observed within these subgroups. Compared with the number of lower-risk women, a similar or smaller num ber of high-risk women needed to be treated to prevent 1 fracture. For example, 8 women aged 75 years or older compared with 9 women younger than 75 years, or 4 women with 2 or more existing vertebral fractures compared with 16 women with 1 existing vertebral fracture, needed to be treated with alendronate for 5 years to prevent 1 new vertebral fra cture. Conclusions: Alendronate effectively reduces fracture risk in p ostmenopausal women with vertebral fractures and low BMD, including th ose women at highest risk because of advanced age or severe osteoporos is. Since the risk reductions observed with alendronate treatment were consistent within fracture risk categories, more fractures were preve nted by treating women at highest risk.