Skeletal response of ovariectomized rats to low and high doses of 17 beta-estradiol

Recent studies indicate that the mode of action of estrogen in preventing bone loss due to ovarian hormone deficiency may vary with the dose of the hormone. In this study four groups of ovariectomized animals were maintained on a wide range of doses of 17 beta-estradiol to further determine the relationship of dose to the mechanism by which estrogen prevents ovarian hormone deficiency bone loss. Ovariectomy caused a significant decrease in bone density and cancellous bone volume at the proximal metaphysis of the tibia. The decrease was prevented in a dose-dependent manner by estradiol. The rate of bone apposition in cancellous bone in the proximal tibia was increased by ovariectomy, and inhibited in a dose-dependent manner by estradiol. Similarly, ovariectomy increased the excretion of urinary hydroxyproline, an index of the rate of bone turnover, and serum alkaline and tartrate-resistant acid phosphatase. The increases were prevented in a dose-dependent manner by estradiol. In addition, the very high dose of estradiol, but not the lower doses, caused a marked (50%) decrease in serum osteocalcin. Our interpretation of these findings is that the low to very high doses of estradiol used in this study decreased the progression of the bone loss due to ovariectomy by suppression of the rate of bone turnover that involved the depression of both osteoclastic resorption and osteoblastic bone formation.