Bone-cell changes in estrogen-induced bone-mass increase in mice: dissociation of osteoclasts from bone surfaces

Early studies in certain avian and mammalian species have described estrogen-associated bone-cell changes, which were based on bone cells that were neither quantified nor identified histochemically (osteoclasts). In the experiments described here, weanling female mice were given a pharmacological dose of 17 beta-estradiol benzoate (1 mg/week) for 1 and 4 weeks, and changes in osteoclasts and osteoblasts were assessed in tibial metaphyses and diaphyses. In the proximal metaphysis, the number of osteoclasts/mm surface length was significantly reduced by estrogen at 1 week (43%) and 4 weeks (64%), which was accompanied by significant increases in the number of osteoclasts in the marrow space not in contact with bone surfaces (no./mm2: 382% and 999%, respectively). These increases, along with observations of decreased osteoclast size (19%), of changes in osteoclast morphology, and of numerous acid-phosphatase-positive fragments in the marrow space, suggest that estrogen treatment causes the dissociation and disintegration, and thus decreased activity, of osteoclasts. The above changes were accompanied by more than 48% increases in the number of trabecular osteoblasts. In the diaphysis, the number of endosteal osteoclasts was significantly decreased by estrogen at 1 week (32%), but was not significantly changed at 4 weeks. These changes were attended by significant increases in the number of osteoclasts in the marrow space not in contact with bone surfaces (no./mm2: 393% at 1 week and 342% at 4 weeks). The number of endosteal osteoblasts was also increased by estrogen at 1 week (132%), and so was the size of endosteal osteoblasts (39% at 1 week and 81% at 4 weeks). Comparable results were obtained when a lower dose of 17 beta-estradiol benzoate (20 micrograms/week) was given to ovariectomized mice. The increase in bone mass and its associated cell changes following estrogen treatment were also found in athymic nude mice, suggesting that these bone/bone cell changes are independent of the thymus.