The physiological role of gonadal androgens in regulating bone metabolism is not established. To determine if androgens antagonize the changes in cortical bone after gonadectomy, we treated orchiectomized (ORX) rats with testosterone (T) and 5 alpha-dihydrotestosterone (DHT), and ovariectomized (OVX) rats with the afore-mentioned androgens, as well as the synthetic androgen fluoxymesterone (Fl) and the nonsteroidal estrogen diethylstilbestrol (DES). OVX resulted in a rapid, sustained increase in periosteal bone formation at the tibial diaphysis, whereas ORX resulted in decreased bone formation. Androgen treatment stimulated bone formation in ORX rats and suppressed bone formation in OVX rats. A large dose of DES suppressed bone formation in OVX rats to values below the intact controls. The results of these studies demonstrate that androgens counteract the changes in cortical bone formation after gonadectomy in females as well as males, and thereby reestablish the sex difference observed in intact rats.

The effects of the nonsteroidal antiestrogen tamoxifen were determined on trabecular bone mass in the proximal tibial metaphysis of intact and ovariectomized rats. Rats were ovariectomized at the beginning of the study. On day 7 of the study, 5-mg slow release pellets of tamoxifen or placebo were implanted sc. All of the rats were killed on day 28 of the experiment. Sections of the proximal tibial metaphysis were stained for acid phosphatase and evaluated histomorphometrically. Ovariectomy resulted in marked loss of bone. Compared to the values in sham-operated animals, the trabecular bone at a sampling site in the secondary spongiosa of ovariectomized rats was reduced by more than 60%, the length of trabecular bone surface covered by osteoclasts was increased by 563%, the percentage of trabecular bone surface covered by osteoclasts was increased by 567%, the mean osteoclast size was increased by 84%, and the number of nuclei per osteoclast was increased by 38%. In contrast, treatment of ovariectomized rats for 3 weeks with tamoxifen restored the histomorphometric measurements to values comparable to those in sham-operated animals. 17 beta-Estradiol increased trabecular bone fractional area in ovariectomized and sham-operated rats, and administration of tamoxifen to estrogen-treated, ovariectomized, and sham-operated animals produced a further increase in trabecular bone. In summary, 1) ovariectomy resulted in large increases in both the number and activity of osteoclasts, 2) the increased bone resorption associated with ovariectomy produced a net loss of trabecular bone, and 3) treatment of ovariectomized rats with tamoxifen prevented these skeletal changes. The results indicate that in the rat, tamoxifen mimics the effects of estrogen on trabecular bone at concentrations that are not uterotropic.

The effect of chronic alcohol consumption on the skeleton was investigated in rats. The treated group received ethanol administered as 38% of caloric intake in a liquid diet (Sustacal) for 10 months. The control rats were pair weighted to the ethanol-treated animals throughout the study; the growth curves of the two groups were the same. The controls were given the same liquid diet except that dextrin:maltose (3:1) was substituted isocalorically for ethanol. Ethanol-treated rats did not differ from the pair-weighted controls in mean serum calcium, phosphorous, or creatinine. In contrast, serum magnesium was reduced (p less than 0.02) in alcohol-treated rats. Ethanol treatment also resulted in changes in the serum concentrations of vitamin D metabolites; serum 25-hydroxyvitamin D3 was increased (p less than 0.001), while serum 1,25-dihydroxyvitamin D3 was decreased (p less than 0.01). Tibial length was reduced in ethanol-treated rats (p less than 0.05) but there was no change in femoral length. Medullary area was increased in tibial diaphyses from alcohol-treated rats compared to weight matched control animals (p less than 0.01), indicating a net increase in resorption. The cross-sectional area of the tibial diaphysis of ethanol-treated rats was the same as the matched controls. Trabecular bone was decreased in the tibial metaphysis of ethanol-treated rats compared to the matched controls (p less than 0.05) indicating a net loss of trabecular bone. Ethanol treatment did not have an effect on the organic weight of the femur but the ash weight was reduced (p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)