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A Randomized Controlled Trial

Steven T. Harris, MD; Nelson B. Watts, MD; Harry K. Genant, MD; Clark D. McKeever, MD; Thomas Hangartner, PhD; Michael Keller, MD; Charles H. Chesnut III, MD; Jacques Brown, MD; Erik F. Eriksen, MD; Mohammad S. Hoseyni, PhD; Douglas W. Axelrod, MD, PhD; Paul D. Miller, MD; for the Vertebral Efficacy With Risedronate Therapy (VERT) Study Group

JAMA. 1999;282:1344-1352.

Context  Risedronate, a potent bisphosphonate, has been shown to be effective in the treatment of Paget disease of bone and other metabolic bone diseases but, to our knowledge, it has not been evaluated in the treatment of established postmenopausal osteoporosis.

Objective  To test the efficacy and safety of daily treatment with risedronate to reduce the risk of vertebral and other fractures in postmenopausal women with established osteoporosis.

Design, Setting, and Participants  Randomized, double-blind, placebo-controlled 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 centers in North America conducted between December 1993 and January 1998.

Interventions  Subjects were randomly assigned to receive oral treatment for 3 years with risedronate (2.5 or 5 mg/d) or placebo. All subjects received calcium, 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  Incidence of new vertebral fractures as detected by quantitative and semiquantitative assessments of radiographs; incidence of radiographically confirmed nonvertebral fractures and change from baseline in bone mineral density as determined by dual x-ray absorptiometry.

Results  The 2.5 mg/d of risedronate arm was discontinued after 1 year; in the placebo and 5 mg/d of risedronate arms, 450 and 489 subjects, respectively, completed all 3 years of the trial. Treatment with 5 mg/d of risedronate, compared with placebo, decreased the cumulative incidence of new vertebral fractures by 41% (95% confidence interval [CI], 18%-58%) over 3 years (11.3% vs 16.3%;P=.003). A fracture 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 over 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 during risedronate treatment was histologically normal. The overall safety profile of risedronate, including gastrointestinal safety, was similar to that of placebo.

Conclusions  These data suggest that risedronate therapy is effective and well tolerated in the treatment of women with established postmenopausal osteoporosis.

Author Affiliations: University of California, San Francisco (Drs Harris and Genant); Department of Medicine, Emory University, Atlanta, Ga (Dr Watts); reSearch for Health/Health Advance, Houston, Tex (Dr McKeever); Biomedical Imaging Laboratory, Wright State University, Dayton, Ohio (Dr Hangartner); San Diego Arthritis & Osteoporosis Medical Clinic, San Diego, Calif (Dr Keller); Department of Nuclear Medicine, University of Washington, Seattle (Dr Chesnut); Department of Rheumatology, Hospital Center, Laval University, Ste-Foy, Quebec (Dr Brown); Department of Endocrinology, Aarhus Amtssygehus, Aarhus, Denmark (Dr Eriksen); Procter & Gamble Pharmaceuticals, Cincinnati, Ohio (Drs Hoseyni and Axelrod); and Colorado Center for Bone Research, Lakewood (Dr Miller).

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