THE EFFECT OF THE ANTIESTROGEN TAMOXIFEN ON BONE-MINERAL DENSITY IN NORMAL LATE POSTMENOPAUSAL WOMEN

PURPOSE: TO assess the effect of the antiestrogenic agent tamoxifen on bone mineral density in normal late postmenopausal women. METHODS: a randomized, double-blind, placebo-controlled was was performed with 57 healthy, late postmenopausal women (mean 11 +/- 7 years since menopau se). Subjects were assigned to take either tamoxifen 20 mg/d or placeb o for 2 years, Total body, lumbar spine, and proximal femoral (femoral neck, Ward's triangle, trochanter) bone mineral densities were measur ed every 6 months using dual-energy x-ray absorptiometry. Serum and ur ine indices of bone turnover were measured at baseline, 6 months, and 2 years. RESULTS: In the women given tamoxifen, the mean bone mineral density of the lumbar spine increased by 1.4%, while that in the women given placebo declined by 0.7% (P < 0.01 for difference between group s). Total body bone mineral density declined in both groups, but less so in the tamoxifen-treated women (P < 0.05). at both sites, the effec t of tamoxifen was maximal after 1 year, with no further separation of the groups thereafter. There was no significant effect of tamoxifen o n bone mineral density in the proximal femur. Tamoxifen produced signi ficant falls in serum alkaline phosphatase (P < 0.0001), ionized calci um (P < 0.0001), and phosphate (P < 0.01), and in urinary excretion of hydroxyproline, n-telopeptides, and calcium IP (P < 0.05 for each). C ONCLUSIONS: In normal late postmenopausal women, tamoxifen at a dose o f 20 mg/d exerts a small protective effect on bone mineral density, co mparable in magnitude to that of calcium supplementation and less than that of either estrogen or the bisphosphonates. Tamoxifen is unlikely to supersede any of these therapies in the management of postmenopaus al osteoporosis.