Alendronate and estrogen-progestin in the long-term prevention of bone loss: Four-year results from the early postmenopausal intervention cohort study - A randomized, controlled trial

Background: Up to 3 years of treatment with alendronate, 5 mg/d, prevents p ostmenopausal bone loss. Objective: To determine whether the effect of alendronate is sustained at 4 years of treatment and persists after treatment is discontinued. Design: Randomized, controlled trial. Setting: United States and Europe. Participants: 1609 postmenopausal women 45 to 59 years of age. Intervention: Participants were randomly assigned to receive oral alendrona te, 5 mg/d or 2.5 mg/d; placebo; or open-label estrogen-progestin, Women in the alendronate groups received alendronate for the first 2 years of the s tudy. Treatment was then continued without change or replaced with placebo for the last 2 years of the study. Measurements: Annual measurement of bone mineral density. Results: By year 4, the bone mineral density of participants in the placebo group had decreased by 1% to 6% (P < 0.001). Four years of treatment with 5 mg of alendronate per day increased bone mineral density at the spine (me an change [+/- SE], 3.8% +/- 0.3%), hip (mean, 2.9% +/- 0.2%), and total bo dy (mean, 0.9% +/- 0.2%) (P < 0.001 overall). By year 4, bone mineral densi ty at most skeletal sites was greater in participants who switched from ale ndronate to placebo than in those who continuously received placebo. In yea rs 3 and 4, bone loss in participants who switched from alendronate to plac ebo was similar to that seen during years 1 and 2 in those who continuously received placebo. Compared with 5 mg of alendronate per day, estrogen-medr oxyprogesterone acetate produced similar increases in bone mineral density and estradiol-norethisterone acetate produced increases that were substanti ally greater. Conclusions: Four years of treatment with alendronate or estrogen-progestin prevented postmenopausal bone loss. A residual effect was seen Z years aft er alendronate therapy was stopped; however, continuous alendronate treatme nt was more effective in preventing postmenopausal bone loss than 2 years o f alendronate followed by Z years of placebo.