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Building bone. Stress spurs the production of new bone (top, white), but not in mice lacking ER-a (bottom).

Aging Bones Ignore Hormones

After menopause, women's bones weaken, but researchers don't understand why. A new study, reported in the 24 July issue of Nature, suggests that women suffer from bone loss, or osteoporosis, due to a decline in estrogen receptors. In experiments with mice, the researchers found that a particular estrogen receptor is necessary for bone cells to replenish their numbers in response to mechanical strain.

Every move we make deforms our bones ever so slightly. Bone cells normally adjust to repeated stresses by building up new bone tissue, which is constantly being recycled. But at menopause, this adaptive response becomes less effective. Bones waste away and become prone to fractures. The dip in estrogen levels that accompanies menopause has always been a prime suspect in osteoporosis, but recent studies show that estrogen levels themselves do not determine bone cells' response to strain. The new study suggests another culprit: declining levels of an estrogen receptor known as ER-a.

Lance Lanyon of the Royal Veterinary College in London and colleagues tested the resilience of bone in two groups of mature female mice--normal mice and ones engineered to lack ER-a. Three times a week, the mice were anesthetized while a machine pressed down on their forelimbs. After 2 weeks, normal mice had formed three times more new bone in the limbs than had mice without ER-a. A set of experiments in cultured bone cells confirmed that the human form of ER-a can restore the adaptive response to strain in cells where it is lacking.

The researchers propose that declining levels of ER-a in postmenopausal women may cause their bones to lose mass and weaken. Indeed, some studies have found that as estrogen levels decline in women, the number of estrogen receptors--including ER-a--falls too.

The study shows that two factors important in maintaining bone mass in adult skeleton, estrogen and mechanical strain, act through a common pathway, says endocrinologist Lawrence Riggs of the Mayo Medical School in Rochester, Minnesota. And that, he says, "has major implications for explaining the mechanism of postmenopausal bone loss in women."

Related sites
Information about osteoporosis
A primer on estrogen receptors