Postmenopausal women who discontinue alendronate after 5 years of treatment may experience a moderate decline in bone mineral density but are not at a significantly higher risk for fracture compared with those who continue alendronate for an additional 5 years, reported Dennis M. Black, Ph.D., of the University of California, San Francisco, and his colleagues.
“For many women, discontinuation of alendronate after 5 years for up to 5 more years does not significantly increase fracture risk, but women at high risk of clinical vertebral fractures, such as those with vertebral fracture or very low [bone mineral density], may benefit by continuing beyond 5 years,” Dr. Black wrote (JAMA 2006;296:2927–38).
This conclusion was based on findings from a 5-year extension of the Fracture Intervention Trial (FIT), a randomized, placebo-controlled trial designed to evaluate the effect of daily alendronate on bone mineral density (BMD) and fracture risk in postmenopausal women with low BMD. The FIT Long-Term Extension (FLEX) study was open to women who had been assigned to the alendronate treatment arm in FIT and who had completed at least 3 years of alendronate treatment. Women with a total hip BMD of less than 0.515 g/cm
Participants were randomly assigned to receive daily treatment with 10 mg alendronate (30%), 5 mg alendronate (30%), or placebo (40%). The primary study end point was total hip BMD.
Of 1,099 women participating in FLEX, 437 were assigned to placebo, 329 were assigned to 5 mg alendronate, and 333 were assigned to 10 mg alendronate.
The treatment groups did not significantly differ in adverse events or other safety parameters during the study, and no cases of osteonecrosis were observed.
After 5 years, total hip bone mineral density declined 3.38% (0.22) from baseline values in the placebo group and 1.02% (0.18) in the combination of the two alendronate groups for a mean difference of 2.36% (95% CI: 1.81%–2.90%; P less than .001). The combined alendronate group experienced a mean 5.26% (0.24) increase from FLEX baseline in lumbar spine BMD compared with a mean 1.52% (0.29) increase in the placebo group (mean difference of 3.74%; 95% CI: 3.03%–4.45%, P less than .001). Notably, mean BMD levels remained at or above FIT baseline levels in all treatment groups after 5 years.
The two alendronate groups did not differ significantly in their incidence of total clinical fractures or nonvertebral fractures.
However, the risk of clinical vertebral fractures was significantly higher in the placebo group (5.3%) than in the combined alendronate group (2.4%).