Effect of Alendronate on the Age-Specific Incidence of Symptomatic Osteoporotic Fractures

Abstract

Analyses of data from 3658 postmenopausal women with osteoporosis enrolled in the Fracture Intervention Trial showed that alendronate is effective in reducing the risk of symptomatic osteoporotic fractures across a spectrum of ages. Most osteoporosis studies examine the relative risk of fracture based on the entire duration of treatment. Because older patients tend to be at higher risk for osteoporosis-related fractures, this analysis examined the effect of alendronate treatment on the relative risk of fracture in terms of the age that patients attained during the study. We studied 3658 postmenopausal women with osteoporosis 55-80 years of age at baseline enrolled in the Fracture Intervention Trial, a large randomized, double-blind, placebo-controlled study. Patients were treated with placebo or with alendronate at a daily dose of 5 mg for 2 years followed by 10 mg for an additional 1-2.5 years, and monitored for clinical fractures. Age, rather than study time, was the dynamic variable in our analysis. The relative risk reductions for hip, clinical spine, and wrist fractures were constant across age groups, without evidence of a decline at older ages. Specifically, alendronate reduced the risk of clinical fracture by 53% at the hip (relative risk [RR] = 0.47; 95% CI = 0.27-0.81; p < 0.01), 45% at the spine (RR = 0.55; 95% CI = 0.37-0.83; p < 0.01), and 31% at the wrist (RR = 0.69; 95% CI = 0.50-0.98; p = 0.038). In addition, alendronate produced a significant risk reduction of 40% (RR = 0.60; 95% CI = 0.47-0.77; p < 0.01) for the composite event of clinical hip, spine, and wrist fractures. As a consequence of the constant relative risk model, the absolute risk reduction with alendronate treatment increased with age because of the age-related increase in fracture risk in the placebo group. The absolute risk reduction for the composite event (hip, spine, and wrist fractures together) for alendronate treatment versus placebo was 65, 80, 111, and 161 women with fractures per 10,000 PYR for the 55 to <65, 65 to <70, 70 to <75, and 75-85 year age groups, respectively. These data show that alendronate is effective in reducing the risk of symptomatic osteoporotic fractures across a spectrum of ages. The effectiveness is somewhat greater in patients with femoral neck T score < or = -2.5 than in those with a T score < or = -2.0.