REDUCED CHONDROCLAST DIFFERENTIATION RESULTS IN INCREASED CANCELLOUS BONE VOLUME IN ESTROGEN-TREATED GROWING RATS

These studies were designed to investigate the role of altered growth processes in mediating estrogen-induced changes in cancellous bone volume in growing female rats. Ovariectomy resulted in an increase in the longitudinal growth rate of the tibia throughout the growth period and estrogen treatment of ovariectomized (OVX) rats resulted in a dose-dependent decrease in longitudinal growth. Estrogen treatment also resulted in decreases in growth plate thickness, chondroclast number in the zone of vascular invasion, and osteoclast number in the secondary spongiosa. There were simultaneous increases in mineralized cartilage in the zone of vascular invasion; total mineralized tissue, mineralized cartilage, and bone in the primary spongiosa; and bone in the secondary spongiosa. Ovariectomy increased and estrogen treatment of OVX rats decreased [H-3]thymidine-labeled nuclei in chondroclasts after 24 h, but after 7 days, the labeling indices were similar in the OVX and intact groups and only slightly decreased in the estrogen-treated rats. We interpret these results as evidence that estrogen impairs chondroclast differentiation. We propose that this impairment leads to decreased chondroclast number and reduced resorption of mineralized cartilage in the zone of vascular invasion, which, in turn, results in an increased cancellous bone volume.