Raloxifene, recently labeled by the U.S. Food and Drug Administration for prevention of postmenopausal osteoporosis, is a benzothiophene that acts on estrogen receptors. Previously, only estrogen and alendronate were labeled for this. Consultants for The Medical Letter on Drugs and Therapeutics reviewed the data on raloxifene, a selective estrogen receptor modulator that is similar to tamoxifen.

Tamoxifen acts as an estrogen agonist in bone and as an estrogen antagonist in the breast, but because of its partial estrogen agonist function in the uterus, its use increases the risk of endometrial cancer. Raloxifene, by comparison, has an estrogen agonist effect on bone and antagonist effect on the breast and the uterus. A double-blind study of 601 postmenopausal women compared the effect of 30, 60 or 150 mg of raloxifene with that of placebo. All of the women in the study also took elemental calcium daily.

Bone density in the lumbar spine, hip and femoral neck decreased in the women who took placebo and increased with all doses of raloxifene. Endometrial thickness measured by sonography remained the same for all study groups. Levels of low-density lipoprotein cholesterol decreased more in women taking raloxifene.

Previous comparisons have shown that raloxifene is slightly less effective in reducing bone loss in the hip than estrogen plus a progestin, or alendronate, and its effect on the lumbar spine is about one half that of older drugs. No direct comparisons with other drugs are available. Raloxifene is excreted almost entirely in the feces, and about 60 percent of the drug is absorbed when taken orally. Cholestyramine decreases the absorption of raloxifene by 60 percent, thus the manufacturer recommends that the two drugs be taken two hours apart. Raloxifene decreases the effect of warfarin. Hot flashes and leg cramps may occur. Like estrogen, raloxifene increases the risk of venous thromboembolism. Because it is a known teratogen, pregnant women should not take raloxifene. In short-term studies, raloxifene has not been shown to increase the incidence of cancer. Raloxifene is available in 60-mg tablets and is taken once daily without regard to meals. A 30-tablet bottle costs the pharmacist $59.40.

The Medical Letter consultants advise, based on data from one short-term study, that raloxifene may be effective in preventing postmenopausal bone loss without increasing the risk of breast or uterine cancer. Long-term studies are needed to determine the safety and effectiveness of raloxifene.