IN THE OVARIECTOMIZED RAT, TAMOXIFEN CONSERVES BONE SIMILARLY IN PARATHYROID-INTACT AND PARATHYROIDECTOMIZED ANIMALS

To examine the ability of tamoxifen (TAM) to conserve bone in the estrogen-deficient ovariectomized (OVX) rat in the presence and absence of parathyroid hormone (PTH) six groups of rats with Ca-45-labeled bones were studied for 12 weeks. Rats were OVX, parathyroidectomized (PTX), or given sham operations and treated with TAM (10 mg/kg body wt./wk subcutaneously) or TAM-vehicle. Treatments were: group 1 = Sham-OVX; group 2 = Sham-OVX + TAM; group 3 = OVX; group 4 = OVX + TAM; group 5 = OVX + PTX; and group 6 = OVX + PTX + TAM. To monitor bone resorption serial measurements of urinary hydroxyproline and Ca-45 excretion were made during the study. Ovariectomy raised these markers of bone breakdown and caused significant osteopenia, whereas TAM prevented ovariectomy increasing urinary hydroxyproline or Ca-45 and conserved bone. Final total body calcium values (TBCa) in groups 1-6, respectively, were (mg +/- SD): 3240 +/- 300; 3260 +/- 289; 2750 +/- 231; 3212 +/- 312; 2742 +/- 199; and 3387 +/- 252. Thus ovariectomy reduced TBCa similarly in the presence and absence of the parathyroids (p < 0.001). In contrast TAM fully protected both PT-intact and PTX rats from the osteopenic effect of ovariectomy, despite the fact that PTX rats had a lower rate of bone turnover than PT-intact rats. However, TAM-treated OVX rats had shorter femora than OVX rats given TAM-vehicle, suggesting that TAM sup presses growth of the long bones to some degree in estrogen-deficient animals. We conclude that, in the rat, TAM conserves the skeleton from estrogen-deficiency bone loss independently of changes in PT function. Estrogen-deficiency bone loss is no greater in rats with a high rate of PTH-mediated bone breakdown than in rats with a low rate of PTH-mediated bone turnover.