1982 Canadian Family Physician • Le Médecin de famille canadien ❖ VOL 47: OCTOBER • OCTOBRE 2001 CR IT ICAL APPRAISAL ❖ VALUATION CRITIQUE Ettinger B, Black DM, Mitlak BH, Knickerbocker RK, Nickelsen T, Genant HK, et al. Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial. JAMA 1999;282(7):637-45. Research question Does raloxifene reduce risk of vertebral fractures in postmenopausal women with osteoporosis? Type of article and design Multicentre, randomized, blinded, placebo-controlled trial of therapy. Relevance to family physicians Osteoporosis has long been a major public health con- cern. 1,2 Health care costs and human costs in reduced quality of life are high. Fractures due to osteoporosis result in physical deformity, acute and chronic symp- toms, impaired physical and emotional function, decreased enjoyment of life, and shorter lifespan. 3 Estrogen therapy can preserve bone mineral density (BMD) in both younger and older postmenopausal women. 4 It has, however, undesirable effects on many other organs. Debate continues as to its effect on risk of breast cancer. 5 To date, no large randomized clinical trials have evaluated its efficacy against fractures. 6 Raloxifene, a tissue-specific estrogen agonist, has estrogen- like effects on bone and serum lipid levels, but does not affect the endometrium or breast. 7 It has been associated, however, with a decreased incidence of estrogen-responsive malignancies in the breast and endometrium. 8 Raloxifene’s effects on BMD, serum cholesterol concentrations, and the uterine endometrium in healthy postmenopausal women 6 have been reviewed elsewhere. 9 We now look at whether raloxifene has any efficacy in preventing fractures, especially in postmenopausal women with osteoporosis. Overview of study and outcomes This multicentre trial took place in 25 countries. It began in 1994 and had 36 to 40 months of follow up. A total of 7705 postmenopausal women aged 31 to 80 years with osteoporosis were divided into two study groups (group 1 with BMD score <–2.5, group 2 with radiographically apparent fractures) and randomly assigned to placebo or one of two daily doses of raloxifene: 60 mg or 120 mg. Placebo and treatment arms all received supplemental calcium and cholecal- ciferol. The study’s primary end point was radi- ographically apparent new vertebral fractures and changes in BMD. Another end point was nonverte- bral fractures. Inclusion criteria were postmenopausal for at least 2 years and no severe or long-term disabling conditions except osteoporosis, which was defined as low BMD, radiographically apparent vertebral fractures, or both. Women were excluded if they had a history of bone diseases other than osteoporosis, estrogen-related symptoms or carcinoma, nonskin cancer, thromboem- bolic disorders, endocrine disorders requiring therapy (except for type 2 diabetes or hypothyroidism), active renal lithiasis, abnormal hepatic function, untreated malabsorp- tion, any medications that would affect BMD (eg, androgen, calci- tonin, or bisphosphonate) within the previous 6 months, or creati- nine levels > 225 μ mol/ L (2.5 mg/ dL), or if satisfactory thoracic and lumbar radiographs could not be obtained. Dr Hathirat was an Academic Fellow from Thailand in the Department of Family and Community Medicine at the University of Toronto in Ontario when this article was written. Dr Evans practises in the Department of Family and Community Medicine at the Toronto Western Hospital, University Health Network, and teaches in the Department of Family and Community Medicine at the University of Toronto. Does raloxifene reduce risk of vertebral fractures? Is this another, brighter way to treat osteoporosis? Saipin Hathirat, MD Michael F. Evans, MD, CCFP Critical Appraisal reviews important articles in the literature relevant to family physicians. Reviews are by family physicians, not experts on the topics. They assess not only the strength of the studies but the “bottom line” clinical impor- tance for family practice. We invite you to com- ment on the reviews, suggest articles for review, or become a reviewer. Contact Coordinator Michael Evans by e-mail michael.evans@ utoronto.ca or by fax (416) 603-5821