Risedronate Reverses Bone Loss in Postmenopausal Women With Low Bone Mass: Results From a Multinational, Double-Blind, Placebo-Controlled Trial

Abstract

This study evaluated risedronate, a bisphosphonate used to treat Paget’s disease of bone, for effectiveness and safety when used to prevent or reverse loss of bone mineral density (BMD) in postmenopausal women with low bone mass. A total of 543 women up to age 80 years who were at least 1 year postmenopausal were entered into a randomized, double-blind, placebo-controlled study in which patients received risedronate in a dose of 2.5 or 5 mg. BMD was measured in the lumbar spine, femoral neck, and trochanter. The two treatment groups and placebo recipients had comparable BMD in the lumbar spine at baseline. At least 2 years of treatment were completed by 355 participants. BMD at the lumbar spine increased by 4 percent after 2 years in patients given 5 mg of risedronate, and a lesser increase was noted in those given 2.5 mg. Patients receiving placebo had no change. Benefit was not a function of time since menopause (Fig. 1). Changes in BMD at the femoral neck and trochanter were less impressive than in the spine except for a nearly 3 percent increase at the trochanter after 2 years of 5 mg of risedronate. Serum levels of bone-specific alkaline phosphatase decreased by nearly one-fourth after 2 years of treatment with 5 mg of risedronate and increased by 8 percent on average in patients taking the placebo (Fig. 2). The reduction in the N-telopeptide/creatinine ratio after 2 years on 5 mg of risedronate was substantially greater than in the placebo group. There were positive trends toward a reduction in vertebral fractures, mostly with the higher dose of risedronate. Adverse events, including gastrointestinal erosion and ulceration, were comparably frequent in all groups. Risedronate was a rapidly effective and well-tolerated treatment for postmenopausal osteoporosis in this trial, regardless of time since menopause.Fig. 1: Change in BMD at the lumbar spine during treatment with 5 mg of risedronate (▪), 2.5 mg of risedronate (▴), or placebo (○), stratified into: A) ≤5 years postmenopausal or B) >5 years postmenopausal. ***, P < .001 versus placebo. Values are means ± SEM.Fig. 2: Changes in A) serum concentrations of bone-specific alkaline phosphatase and B) NTx/creatinine during treatment with 5 mg of risedronate (▪) or placebo (○). ***, P < .001 versus placebo. Values are means ± SEM.J Clin Endocrinol Metab 2000;85:1895–1900