The efficacy of alendronate in reducing the risk for vertebral fracture in japanese patients with osteoporosis: A randomized, double-blind, active-controlled, double-dummy trial

Abstract 

Background: Alendronate, a potent antiresorptive agent, effectively reduces fracture risk. Alendronate increases bone mineral density (BMD) and decreases bone turnover markers to a similar extent in white and Asian people, including Japanese. However, no large trials of this drug have been conducted specifically in the Japanese population.

Objective: This study examined the antifracture efficacy of alendronate in Japanese patients.

Methods: We conducted a 2-year, multicenter, randomized, double-blind, active-controlled, double-dummy trial of women and men with osteoporosis in Japan, with radiographically diagnosed vertebral fracture being the primary end point. Patients were randomized to receive alendronate 5 mg/d or alfacalcidol 1 gmg/d.

Results: A total of 365 patients (349 women, 16 men; mean age, 73 years) were enrolled in the study. At the end of 24 months, spinal BMD was significantly increased versus baseline by a mean of 6.9% in the alendronate-treated group (P < 0.001) and 1.5% in the alfacalcidol-treated group; the median increases in BMD at 24 months versus baseline were 8.3% and 1.4%, respectively. The incidence of vertebral fracture >6 months after randomization (the primary end point) was significantly reduced by 66% (relative risk [RR], 0.34; 95% CI, 0.15–0.74) in the alendronate group (4.3% vs 12.7% incidence). When all fractures during the 24 months were considered, the incidence of multiple (≥2) vertebral fractures also was reduced significantly by 67% (RR, 0.33; 95% CI, 0.11–0.96; 2.4% vs 7.3% incidence). The difference in overall incidence (≥1 vertebral fracture during all 24 months) was not significant (12.2% vs 16.7%), implying that risk reductions (relative to the active control) improved after 6 months. This is consistent with bone biology theory, which predicts that several months are required to refill existing resorption sites and increase bone strength more than the active control. Thus, theory predicts that several months would be required to increase bone strength and reduce fracture risk relative to the active control. This study was limited to Japanese participants, but the findings are consistent with results reported from similar studies among white people. Furthermore, because this was an active-controlled trial, it may have underestimated the antifracture efficacy of alendronate relative to a true placebo.

Conclusions: The effectiveness of alendronate in reducing the risk of radiographically defined vertebral fracture in Japanese women and men with osteoporosis is similar to that reported previously in white people. As a consequence, the benefits of alendronate in reducing vertebral and hip fractures can be expected to be substantial and early (beginning at month 6).

Keywords:  vertebral fracture, osteoporosis, clinical trial, alendronate, alfacalcidol, Japanese

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