PRESERVATION OF ECTOPICALLY INDUCED BONE IN THE MOUSE BY ESTRADIOL

The effects of estrogen on bone formation and bone resorption were examined in an experimental model of ectopic bone induction. In this experimental model, ectopic ossicles of uniform size were elicited reproducibly in three weeks by implanting pellets containing murine osteosarcoma derived bone morphogenetic protein (BMP), into the muscles of mice. Thereafter the induced ossicles showed a gradual reduction in bone mass due to negative bone balance. To estimate the effects of estrogen on bone formation and bone resorption, beta-estradiol-3-benzoate was administered exogeneously to host mice from day 21 to day 41 (0.45-mu-g/g body weight, on alternate days, 10 treatments). Radiologic and histologic analysis confirmed the positive effect of estradiol on preserving bone mass over this period. Quantitative analysis showed an increase in the Ca content in ossicles after 21 days of estradiol treatment (139.1% of the baseline value on day 21). In the control group, the bone mass was reduced (47.4% of that on day 21). Bone resorption was determined by the reduction in Ca-45 radioactivity from ossicles prelabeled with this radioisotope before estradiol administration. The rate of loss of the prelabeled Ca-45 radioactivity was suppressed by estradiol (68.8% of prelabeled value in estradiol treated group and 87.7% in control group). The effect of exogeneous estrogen on the bone forming phase of bone turnover in the ossicles was quantified by incorporation of Ca-45 and H-3-proline. These bone formation parameters were increased to 2.2 and 1.9 times higher than those of the control group. Based on these data, estradiol appears to preserve ectopically induced bone in mice, and this effect is derived mainly from enhanced bone formation and partly by suppression of bone resorption during bone turnover.