How long should patients take a bisphosphonate? For most women, the answer seems to be five years.
In a 10-center trial, investigators followed 1,100 older women with osteoporosis who had already taken alendronate (Fosamax) for five years. The patients, aged 55-81, were randomized to one of three groups for five more years: placebo, 5 mg alendronate a day, or 10 mg alendronate a day. During the trial, the women were contacted every three months to encourage medication adherence; participants were examined annually.
At the end of the study, women who had discontinued alendronate (the placebo group) showed a moderate decline in bone mineral density (BMD) and a gradual rise in biochemical markers. However, they experienced no higher nonvertebral fracture risk than those who continued alendronate, and their incidence of clinical vertebral fractures was low (5.3% over the five years). In those who continued taking alendronate, the vertebral fracture incidence was 2.4%. Among women who had existing vertebral fractures or very low BMD, the benefit of continuing on alendronate was significantly higher.
The decline in BMD following discontinuation of alendronate was much lower than that seen after discontinuation of estrogen, raloxifene, or intermittent parathyroid hormone, the researchers reported. Similarly, bone turnover markers increased only gradually after stopping alendronate. The investigators concluded that “for many women, discontinuing alendronate after five years for up to five more years does not significantly increase fracture risk.” However, they added, “women at high risk of clinical vertebral fractures may benefit by continuing beyond five years” (JAMA. 2006; 296:2927-2938).