Estrogen does not restore bone lost after ovariectomy in the rat.

We recently found that 17 beta-estradiol (E2) not only suppresses bone resorption but also stimulates bone formation in the cancellous bone of female rats. This raises the possibility that E2 treatment might restore the bone lost after ovariectomy in the rat. To test this, 13-week-old rats were ovariectomized (ox). After a further 13 weeks the animals were injected with E2 (4 mg or 40 micrograms/kg daily), human calcitonin (hCT) (3 IU/kg daily), (3-amino-1-hydroxypropylidene)-1-bisphosphonate (AHPrBP) (0.3 mg/kg twice per week), or a combination of E2 with hCT or AHPrBP, for 8 weeks. The bone volume at the tibial metaphysis of ox animals was approximately 40% of that of sham-operated controls at the end of the experiment. Although the bone volume of ox rats treated with E2 and/or hCT or AHPrBP was slightly higher than that of untreated ox rats, the increase was not significant. Neither E2 alone nor a combination of E2 with hCT or AHPrBP was associated with a higher bone volume than hCT or AHPrBP alone, suggesting no effect of E2 beyond that of inhibition of bone resorption. Histodynamic indices of bone formation were increased in untreated ox rats compared to controls but suppressed in E2-treated, hCT-treated, and AHPrBP-treated animals. These results emphasize the similar responses of rat and human bone, both of which not only show bone loss with estrogen deficiency, preventable by estrogen administration, but also show an inability of estrogen to restore bone lost as a result of estrogen deficiency.