Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis - A randomized controlled trial

Context Risedronate, a potent bisphosphonate, has been shown to be effectiv e in the treatment of Paget disease of bone and other metabolic bone diseas es but, to our knowledge, it has not been evaluated in the treatment of est ablished postmenopausal osteoporosis. Objective To test the efficacy and sa fety of daily treatment with risedronate to reduce the risk of vertebral an d other fractures in postmenopausal women with established osteoporosis. De sign, Setting, and Participants Randomized, double-blind, placebo-controlle d trial of 2458 ambulatory postmenopausal women younger than 85 years with at least 1 vertebral fracture at baseline who were enrolled at 1 of 110 cen ters in North America conducted between December 1993 and January 1998. int erventions Subjects were randomly assigned to receive oral treatment for 3 years with risedronate (2.5 or 5 mg/d) or placebo. All subjects received ca lcium, 1000 mg/d, Vitamin D (cholecalciferol, up to 500 IU/d) was provided if baseline levels of 25-hydroxyvitamin D were low. Main Outcome Measures I ncidence of new vertebral fractures as detected by quantitative and semiqua ntitative assessments of radiographs; incidence of radiographically confirm ed nonvertebral fractures and change from baseline in bone mineral density as determined by dual x-ray absorptiometry. Results The 2.5 mg/d of risedro nate arm was discontinued after 1 year; in the placebo and 5 mg/d of risedr onate arms, 450 and 489 subjects, respectively, completed all 3 years of th e trial. Treatment with 5 mg/d of risedronate, compared with placebo, decre ased the cumulative incidence of new vertebral fractures by 41% (95% confid ence interval [CI], 18%-58%) over 3 years (11.3% vs 16.3%; P=.003). A fract ure reduction of 65% (95% CI, 38%-81%) was observed after the first year (2 .4% vs 6.4%; P<.001). The cumulative incidence of nonvertebral fractures ov er 3 years was reduced by 39% (95% CI, 6%-61%) (5.2% vs 8.4%; P=.02). Bone mineral density increased significantly compared with placebo at the lumbar spine (5.4% vs 1.1%), femoral neck (1.6% vs -1.2%), femoral trochanter (3. 3% vs -0.7%), and midshaft of the radius (0.2% vs -1.4%). Bone formed durin g risedronate treatment was histologically normal. The overall safety profi le of risedronate, including gastrointestinal safely, was similar to that o f placebo, Conclusions These data suggest that risedronate therapy is effec tive and well tolerated in the treatment of women with established postmeno pausal osteoporosis.