Bone formation appears to be controlled by serotonin, a chemical previously known mainly for its entirely separate role in the brain, researchers are reporting.

The discovery can have enormous implications, osteoporosis experts say, because there is an urgent need for osteoporosis treatments that actually build bone.

Osteoporosis affects 10 million Americans over age 50. It results in bone loss, and its hallmark is fragile bones that break easily. With one exception, current treatments only slow further bone loss rather than increase bone formation. The exception, parathyroid hormone, given by injection, is recommended only for short-term use and costs about $6,700 a year.

But in a paper published online Wednesday in the journal Cell, a team led by Dr. Gerard Karsenty, chairman of the department of genetics and development at the Columbia University College of Physicians and Surgeons, reports the discovery of an unexpected system that appears to control bone formation.

At its heart is serotonin made by the gut rather than the brain, whose role outside the brain had been a mystery. Ninety-five percent of the body's serotonin is made by the gut, but gut serotonin cannot enter the brain because it is barred by a membrane, the so-called blood-brain barrier.

Karsenty reports, though, that gut serotonin can directly control bone formation. It is released into the blood, and the more serotonin that reaches bone, the more bone is lost. Conversely, the less serotonin, the denser and stronger bones become. Karsenty was even able to prevent menopause-induced osteoporosis in mice by slowing serotonin production.

Osteoporosis researchers were dumbfounded by the report.

"I am very excited by this paper," said Dr. J. Christopher Gallagher, an osteoporosis specialist and professor of medicine at Creighton University. "It is a groundbreaking paper. One is completely surprised."

Dr. Ronald Margolis, senior adviser for molecular endocrinology at the National Institute of Diabetes and Digestive and Kidney Diseases, said: "I was astonished. My jaw was dropping."

Dr. Ethel S. Siris, who directs the Toni Stabile Osteoporosis Center at Columbia, cautioned that the work was not with humans but instead involved mice that were engineered to have human genes. "This stuff is really exciting basic - underscore basic - research," Siris said. The story of the serotonin-bone connection began with reports of a rare inherited condition causing fragile bones and blindness. Children with the condition had bones so weak that they needed wheelchairs or devices to assist them in walking.

The problem turned out to be a mutation that inactivated a gene called LRP5.

A few years later, another mutation was found in LRP5 that produced the opposite effect: extremely dense bones and resistance to osteoporosis. In this case, LRP5 was overactive. People with this gene mutation, Karsenty said, had jawbones so dense that it was difficult to extract their teeth.

Osteoporosis researchers jumped on those findings, realizing that LRP5 could hold clues to the disease. But most assumed that LRP5's role was in bone.

Instead, Karsenty discovered that LRP5 acts on serotonin-producing cells in the gut. It blocks an enzyme that converts the amino acid tryptophan to serotonin. The more LRP5, the more the enzyme is blocked, and the less serotonin is made. The gene has no effect, apparently, on brain cells that make serotonin.

After the gut releases serotonin into blood, serotonin travels to bone-forming cells and inhibits their growth.