Osteoporosis could be caused by factors other than declining estrogen levels
New evidence in the April 21, 2006 Cell challenges the long-standing notion that declining estrogen levels alone lead to osteoporosis after women go through menopause. The researchers rather found that high levels of pituitary-derived follicle-stimulating hormone (FSH) cause bone loss in mice. The pituitary is a master gland found at the base of the brain.

What's more, the researchers reported, mice with symptoms of severe estrogen deficiency, lacking either the FSH hormone or its receptor, became resistant to bone loss.

FSH normally triggers egg development and stimulates estrogen production by the ovaries, the researchers explained. As women approach menopause and estrogen levels decline, the pituitary gland responds by releasing more FSH.
Osteoporosis affects nearly 45 million women worldwide with fracture rates that far exceed the combined incidence of breast cancer, stroke, and heart attacks, the researchers said. The disease results from a disruption of the fine balance between bone formation and resorption. After menopause, resorption exceeds new bone formation, leading to a net bone loss that can be slowed by estrogen therapy through mechanisms that have remained somewhat murky, Zaidi said.

However, emerging evidence has begun to cast some doubt on whether estrogen deficiency can fully explain bone loss after menopause, he added. For example, mice without an intact pituitary gland become resistant to the effects of ovary loss on bone density. FSH levels also show a closer correlation than estrogen levels to the rate of bone turnover in postmenopausal women.

The researchers now show that mice lacking FSH or its receptor become resistant to bone loss despite severe loss of ovarian function. In mice with normal ovaries and approximately half the normal concentration of FSH, bone mass increased due to a decline in bone resorption by cells known as osteoclasts, which break down bone. Indeed, they report, FSH stimulates receptors found on the surface of bone-degrading osteoclasts and their precursors, leading to the bone cells' formation and function.