Alterations in osteoclast morphology following long-term 17beta-estradiol administration in the mouse

After 8 weeks of treatment, there was radiologic evidence of severe osteosclerosis and 86% of femoral marrow space was replaced with bone. After 12 weeks histologic studies of treated animals revealed that osteoclasts were positive for tartrate-resistant acid phosphatase but showed markedly abnormal ultrastructure which prevented successful bone resorption.Findings extend our understanding of osteoclast structure and function in the mouse exposed in vivo to high doses of estrogen. Ultrastructural examination showed that osteoclasts from estrogen-treated mice were unable to seal against the bone surface and were unable to form ruffled borders.Although the role of the osteoclast in bone resorption is becoming better understood [1], much remains to be learned about osteoclastogenesis and the exact mechanism of action of anti-resorbing agents on the functional osteoclast. The anti-resorbing agent 17β-estradiol is especially noteworthy because of the association of its decline at menopause with the development of postmenopausal osteoporosis. As previously noted by Liu and Howard, the underlying cellular changes responsible the increased bone formation which follows estrogen administration are still not well characterized [2].In the present report we report findings on alterations in osteoclast morphology following long term administration of high doses of 17β-estradiol to B6D2F1 mice. Development of osteosclerosis and the disappearance of the marrow space in these estrogen-treated mice is an interesting and useful model since marrow stromal cells not only contain the precursors for osteogenic cell lineages, but they also exert important effects on osteoclastogenesis and lymphopoiesis, and modulate the effects of some systemic factors of bone turnover. Osteoclasts, as well as osteoblasts, possess estrogen receptors [3, 4, 5, 6]. Hematopoietic cells also influence osteogenic cell differentiation, and some evidence suggests that mature lymphocytes influence osteoclast and o