Randomized trial of the effects of risedronate on vertebral fractures in women with established postmenopausal osteoporosis

The purpose of this randomized, double-masked, placebo-controlled study was to determine the efficacy and safety of risedronate in the prevention of v ertebral fractures in postmenopausal women with established osteoporosis. T he study was conducted at 80 study centers in Europe and Australia. Postmen opausal women (n = 1226) with two or more prevalent vertebral fractures rec eived risedronate 2.5 or 5 mg/day or placebo; all subjects also received el emental calcium 1000 mg/day, and up to 500 IU/day vitamin D if baseline lev els were low, The study duration was 3 years; however, the 2.5 mg group was discontinued by protocol amendment after 2 years. Lateral spinal radiograp hs were taken annually for assessment of vertebral fractures, and bone mine ral density was measured by dual-energy X-ray absorptiometry at 6-month int ervals. Risedronate 5 mg reduced the risk of new vertebral fractures by 49% over 3 years compared with control (p<0.001), A significant reduction of 6 1% was seen within the first year (p = 0.001). The fracture reduction with risedronate 2.5 mg was similar to that in the 5 mg group over 2 years. The risk of nonvertebral fractures was reduced by 33% compared with control ove r 3 years (p = 0.06). Risedronate significantly increased bone mineral dens ity at the spine and hip within 6 months. The adverse-event profile of rise dronate, including gastrointestinal adverse events, was similar to that of control. Risedronate 5 mg provides effective and well-tolerated therapy for severe postmenopausal osteoporosis, reducing the incidence of vertebral fr actures and improving bone density in women with established disease.