THERAPEUTIC CONTROVERSY Estrogen Replacement in Menopause

A LBRIGHT originally described the importance of ovarian insufficiency in the pathogenesis of osteoporosis and the use of estrogens in treatment (1). Since then a considerable body of evidence has been published to support those concepts (2). Nevertheless, our knowledge base continues to expand, and consequently, there are still some issues that are not well understood regarding the most efficacious and efficient use of hormone prescription for osteoporosis. Certain facts are not disputed. Estrogen deficiency (or ovarian insufficiency) increases bone remodeling primarily by increasing the frequency with which new remodeling units are activated. Whether there is a shift within each remodeling unit in favor of bone resorption is more controversial. But increased remodeling by itself increases the statistical chance of trabecular penetration during resorption, a consequent loss of the template upon which to build new bone and a net loss of bone tissue (2). Estrogen intervention reverses these changes, returning remodeling to premenopausal levels. The consequence is preservation of bone mass, confirmed in numerous clinical trials of a wide variety of design. The effects of estrogen on fracture have mostly been obtained using epidemiological methodology, especially for hip fracture. In general these studies support the view that estrogen administration for even comparatively short periods of time (sometimes defined as 1 yr or more) will reduce the risk of fractures. For vertebral fractures, at least two controlled clinical trials have confirmed the efficacy of estrogen, given for either prevention or treatment (3). What then are the issues about hormones and osteoporosis? First, the mechanism of action of estrogen is still poorly understood. The description of estrogen receptors on bone cells (first osteoblasts and, more recently, some osteoclasts)