The ultrastructural effect of estrogens on bone cells in thyroparathyroidectomized rats

To determine the direct effect of estrogen on bone cells, female rats were thyroparathyroidectomized and given either 200 microng of estradiol cypionate or placebo treatment for 4 to 30 days. After 8 days, an osteosclerosis of the tibial metaphysis developed in rats treated with estrogens. Osteoblasts in estrogen-treated rats were interpreted ultrastructurally to be less active in bone formation than controls. Osteocytes in estrogen-treated rats were inactive compared to osteocytes in control rats which were continuing the process of bone formation. Osteoclasts were decreased in numbers in rats treated with estrogen; however, the electron microscopic characteristics of osteoclasts did not differ from controls. These cellular changes were associated with a severe hypocalcemia in both estrogen-treated and control rats. Serum phosphorus and urinary hydroxyproline were lowered significantly by the administration of estrogen. It is concluded that metaphyseal osteosclerosis develops in estrogen-treated rats independent of parathyroid hormone and calcitonin. The osteoclerosis is due to an effect of estrogens to reduce osteoclast-numbers and a lesser inhibitory effect on the bone-forming activity of osteoblasts and osteocytes. (Am J Pathol 87:311-322, 1977).