The CMAJ supplement containing clinical practice guidelines for osteoporosis1 is a valuable document. However, I find it difficult to understand why raloxifene has been classified as a first-line therapy for the prevention of further bone loss (in postmenopausal women with low bone density) and for the treatment of osteoporosis, given that it has not been shown to significantly reduce the occurrence of hip fractures.2,3 Moreover, in the Multiple Outcomes of Raloxifene Evaluation (MORE) study,2 the incidence of venous thromboembolism was 1% among patients treated with this drug. In my own experience of prescribing this drug for approximately 200 female patients, 2 elderly women with no other known risk factors experienced pulmonary emboli during the first year of treatment, and a third elderly patient was referred to me when deep venous thrombosis developed 1 month after raloxifene was substituted for estrogen therapy.
I feel that the osteoporosis guidelines do not adequately convey the magnitude of the risk for venous thromboembolism during raloxifene therapy. This risk is reported as 3.32 events per 1000 person–years of treatment,1 but because most raloxifene-related events of this type occur during the first year of treatment,4 the risk will appear lower as the duration of follow-up increases. In women under 60 years of age, the risk seems to be low: only 1 case occurred in 859 women treated for 3 years at doses of 30 to 150 mg/day.5 If this is so, the risk in older women may be even higher than the 1% reported in the MORE study.
I am concerned that the designation of raloxifene as a first-line therapy may lead to its being prescribed even when a safer and more effective drug such as alendronate or risedronate would be more appropriate. In women over the age of 60, raloxifene should be used with caution and only after the patient has been informed of the magnitude of the risk for venous thromboembolism (at least 1 in 100).
Edmund R. Yendt Professor Emeritus Department of Medicine Queen's University Kingston, Ont.
References
- 1.Brown JP, Josse RG, for the Scientific Advisory Council of the Osteoporosis Society of Canada. 2002 clinical practice guidelines for the diagnosis and management of osteoporosis in Canada. CMAJ 2002;167(10 Suppl):S1-34. [PMC free article] [PubMed]
- 2.Ettinger B, Black DM, Mitlak BH, Knickerbocker RK, Nickelsen R, 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;282:637-45. [DOI] [PubMed]
- 3.Cranney A, Tugwell P, Zytaruk N, Robinson V, Weaver B, Adachi J, et al. Meta-analyses of therapies for postmenopausal osteoporosis. IV. Meta-analysis of raloxifene for the prevention and treatment of postmenopausal osteoporosis. Endocr Rev 2002;23:524-8. [DOI] [PubMed]
- 4.Evista® (raloxifene) product monograph. Toronto: Eli Lilly Canada Inc.; 2000 Jul 26.
- 5.Johnston CC Jr, Bjarnason NH, Cohen FS, Shah A, Lindsay R, Mitlak BH, et al. Long-term effects of raloxifene on bone mineral density, bone turnover and serum lipid levels in early postmenopausal women: three-year data from 2 double-blind, randomized, placebo-controlled trials. Arch Intern Med 2000;160:3444-50. [DOI] [PubMed]