Mice, Estrogen, and Postmenopausal Osteoporosis

SAMUELS ET AL. have presented evidence that the well known osteosclerotic response of mice to high doses of estrogen is due to de novo bone formation. This finding raises fundamental questions regarding the mechanism of action of estrogen in regulating bone cell metabolism, as well as the appropriateness of the mouse model for studies related to the pathogenesis and treatment of postmenopausal bone loss. However, by considering the physiological effects of estrogen on bone, it will become clear that the effects described by Samuels and co-workers are unlikely to be due to a direct action of estrogen on bone via a conventional pathway. Indeed, the osteosclerotic mouse may be more accurately characterized as a model for complications resulting from a toxic response to estrogen excess.