Skeletal effects of estrogen

Russell T. Turner, B. Lawrence Riggs, Thomas C. Spelsberg

Research output: Contribution to journalReview articlepeer-review

682 Scopus citations


Estrogen affects the skeleton in all species studied. These actions are important to establish the sexual dimorphism of the skeleton and peak bone mass, as well as to maintain mineral homeostasis during reproduction and bone balance in adults. A model outlining the hormone's action on bone cells is illustrated in Fig. 4. Estrogen can act on osteoblast precursors (osteoprogenitors) to increase (endocortical surfaces of birds and mice) or decrease (periosteal and cancellous surfaces of rats) proliferation and differentiation to osteoblasts. Estrogen has variable effects on the proliferation of osteoblast-like cells in culture; the precise action of the hormone may depend upon the extent of cell differentiation. Most studies in whole animals suggest that estrogen has either no effect on or decreases bone formation by mature osteoblasts. Cell culture studies suggest that estrogen acts to increase synthesis and release of osteoblast-derived osteoclast inhibition factors such as TGF-β. On the other hand, osteoblast-derived osteoclast stimulating factors have been proposed but are not yet clearly demonstrated. A pronounced inhibition of osteoclast recruitment by estrogen has been demonstrated in several animal models and in bone marrow culture. Furthermore, estrogen receptors have been demonstrated in isolated osteoclasts, and estrogen inhibits resorptive activity by these cells. The effects of estrogen on osteoclast recruitment and activity result in decreased resorption on trabecular surfaces of cancellous bone and endocortical surfaces of cortical bone. The effect of estrogen to antagonize osteoclast-mediated bone resorption appears to be the most important action of the hormone to preserve bone volume in adult rats and humans. A model for the effects of estrogen on gene expression in bone target cells is illustrated in Fig. 3. This cascade model is based primarily on cell culture studies, although relatively rapid effects of estrogen on mRNA levels for IGF-I and bone matrix proteins have been reported in animals. Estrogen appears to enter bone cells and bind to specific intracellular receptors in a manner analogous to its interactions with other target tissues. Estrogen clearly regulates the expression of nuclear protooncogenes in cultured osteoblasts and osteoclasts that code for transcription factors, the best characterized of which is AP-1. These transcription factors are thought to regulate the expression of other genes, including growth factors such as TGF- β. It is proposed that the cascade of events results in the subsequent regulation of bone cell function, bone formation by osteoblasts, and bone resorption by osteoclasts.

Original languageEnglish (US)
Pages (from-to)275-300
Number of pages26
JournalEndocrine reviews
Issue number3
StatePublished - Jun 1994

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology


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