17-BETA-ESTRADIOL STIMULATES CANCELLOUS BONE-FORMATION IN FEMALE RATS

Estrogen is generally considered to maintain bone mass through suppression of bone resorption. We have previously demonstrated that administration of pharmacological doses of estrogen increases bone formation in rats. Because such high doses of estrogen might induce bone formation through some mechanism other than the estrogen receptor, we have now assessed the effect of more physiological doses of 17-beta-estradiol (E2) on bone formation. Adult female rats (13 weeks and 6 months old) administered E2 (1, 4, 40, 400, and 4 mg/kg daily for 17-21 days) showed a dramatic increase (5- to 8-fold) in cancellous bone formation, attributable to a combination of an increase in the proportion of bone surface actively undertaking bone formation, and an increase in the rate of mineral apposition. Significant anabolism was induced in 6-month-old rats by doses as low as 4-mu-g/kg and in 13-week-old rats by 40-mu-g/kg. Corresponding increases in the proportion of trabecular surface covered by osteoblasts were also observed. Histomorphometric indices of bone resorption were suppressed by estrogen. Estrogen administration caused an increase in bone volume up to 35% over controls, over a 21-day period. Stimulation of bone formation by estrogen showed a similar pattern of dose-responsiveness to recognized physiological targets of E2: suppression of longitudinal growth and uterine growth. These results suggest that stimulation of cancellous bone formation is a physiological action of E2 in the rat.