Monday, October 21, 2002 Posted: 2:04 PM EDT (1804 GMT)

WASHINGTON (AP) -- Researchers have spotted a likely new reason for bone loss that afflicts women and teenage girls who exercise so much or eat so little that they wind up starving themselves.

The focus is on the appetite hormone leptin, which is produced by fat cells and influences brain chemistry that regulates appetite. When fat cells are plump, leptin levels are high. When fat cells are lean, leptin levels are low.

But scientists believe leptin's role gets more complicated in people who eat far less than they require for normal metabolism. In these cases, the body reduces activities that are not vital, and building bone is among them.

Researchers say very low leptin levels prevent bone cells from doing their normal job of building mineral in bone. "The bone goes to sleep," said Dr. Michelle P. Warren of Columbia-Presbyterian Medical Center in New York City. "It's almost a hibernation, to conserve energy."

Warren and colleagues at Columbia-Presbyterian reviewed research, including her own, in the October issue of a medical journal, The Physician and Sportsmedicine.

They focused on girls and women whose energy deficit can lead to a exercise-associated amenorrhea -- the loss of their regular monthly periods. Over time, women with this condition can lose bone, setting them up for increasingly fragile bones, including osteoporosis, as they age.

A low-calorie, high-energy-output imbalance can happen because of the demands of physical activities -- thinness is a valued characteristic in gymnasts and ballet dancers, for instance. It also can happen to those with anorexia, the compulsion to be thin.

"Low leptin levels have been reported in amenorrheic women who exercise regularly at high levels," the journal said.

Previous research had focused on estrogen, which declines in amenorrheic females. That was partly blamed for the shutdown of the reproductive system and loss of bone.

The new research indicates it's not so simple. Estrogen and leptin seem to have different ways of doing damage, Warren said.

While leptin loss retards new bone-building, estrogen loss seems to take the brakes off other cells, called osteoclasts, which strip out old bone mineral, Warren said. The result would be double the bone vulnerability -- growth is inhibited and loss is accelerated.

Exercising this much also reverses what would otherwise be a healthy trend. "Physical activity is important in maintaining bone mass; however, many women tend to exercise excessively, causing hormonal changes that predispose them to an increased risk of fractures," the journal article said.

Warren said the leptin link is worthy of further study. But scientists say there is no sign now that leptin supplements would solve the bone-loss problem.

Warren said the idea sounds promising but research to show it would spur new bone growth has not been done. In addition, the supplement might harm appetite in people who have calorie-balance problems, she said.

It's also too soon for doctors to use leptin levels as an early warning sign of inadequate bone mass, said Dr. Carol Otis of Kerlan-Jobe Orthopaedic Clinic in Los Angeles, who did not work on the review article. Leptin is more properly "a marker of inadequate nutrition and weight loss," she said.

And even use of low leptin levels as an indicator of calorie-balance problems could be misleading, Otis said. Leptin levels vary during the day, so several blood samples would be required, and normal reference levels of leptin in the blood have not been determined, she said.

http://www.cnn.com/2002/HEALTH/diet...n.ap/index.html