Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial. Multiple Outcomes of Raloxifene Evaluation (MORE) Investigators.
BACKGROUND
Raloxifene hydrochloride, a selective estrogen receptor modulator, prevents bone loss in postmenopausal women, but whether it reduces fracture risk in these women is not known.


OBJECTIVE
To determine the effect of raloxifene therapy on risk of vertebral and nonvertebral fractures.


METHODS
The Multiple Outcomes of Raloxifene Evaluation (MORE) study, a multicenter, randomized, blinded, placebo-controlled trial.


METHODS
A total of 7705 women aged 31 to 80 years in 25 countries who had been postmenopausal for at least 2 years and who met World Health Organization criteria for having osteoporosis. The study began in 1994 and had up to 36 months of follow-up for primary efficacy measurements and nonserious adverse events and up to 40 months of follow-up for serious adverse events.


METHODS
Participants were randomized to 60 mg/d or 120 mg/d of raloxifene or to identically appearing placebo pills; in addition, all women received supplemental calcium and cholecalciferol.


METHODS
Incident vertebral fracture was determined radiographically at baseline and at scheduled 24- and 36-month visits. Nonvertebral fracture was ascertained by interview at 6-month-interim visits. Bone mineral density was determined annually by dual-energy x-ray absorptiometry.


RESULTS
At 36 months of the evaluable radiographs in 6828 women, 503 (7.4%) had at least 1 new vertebral fracture, including 10.1% of women receiving placebo, 6.6% of those receiving 60 mg/d of raloxifene, and 5.4% of those receiving 120 mg/d of raloxifene. Risk of vertebral fracture was reduced in both study groups receiving raloxifene (for 60-mg/d group: relative risk [RR], 0.7; 95% confidence interval [CI], 0.5-0.8; for 120-mg/d group: RR, 0.5; 95% CI, 0.4-0.7). Frequency of vertebral fracture was reduced both in women who did and did not have prevalent fracture. Risk of nonvertebral fracture for raloxifene vs placebo did not differ significantly (RR, 0.9; 95% CI, 0.8-1.1 for both raloxifene groups combined). Compared with placebo, raloxifene increased bone mineral density in the femoral neck by 2.1 % (60 mg) and 2.4% (120 mg) and in the spine by 2.6% (60 mg) and 2.7% (120 mg) P<0.001 for all comparisons). Women receiving raloxifene had increased risk of venous thromboembolus vs placebo (RR, 3.1; 95% CI, 1.5-6.2). Raloxifene did not cause vaginal bleeding or breast pain and was associated with a lower incidence of breast cancer.


CONCLUSIONS
In postmenopausal women with osteoporosis, raloxifene increases bone mineral density in the spine and femoral neck and reduces risk of vertebral fracture.
Ettinger
B
B
Division of Research, Kaiser Permanente, Oakland, Calif 94611-5400, USA. bxe@dor.kaiser.org
Black
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Mitlak
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Knickerbocker
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Nickelsen
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Genant
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Christiansen
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Delmas
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Zanchetta
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Stakkestad
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Glüer
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Krueger
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Cohen
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Eckert
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Ensrud
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Avioli
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Lips
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Cummings
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D000328:Adult; D000368:Aged; D015519:Bone Density / Q000187:drug effects; D004967:Estrogens / Q000819:agonists*; D005260:Female; D006801:Humans; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000150:complications / Q000188:drug therapy*; D010880:Piperidines / Q000009:adverse effects / Q000627:therapeutic use*; D011859:Radiography; D020849:Raloxifene Hydrochloride; D012306:Risk; D016103:Spinal Fractures / Q000000981:diagnostic imaging / Q000453:epidemiology* / Q000209:etiology / Q000517:prevention & control
D004967:Estrogens; D010880:Piperidines; D020849:Raloxifene Hydrochloride