Bone finding may point to hope for osteoporosis

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. And 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 on 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 N. 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. Clifford J. Rosen, a senior scientist at the Maine Medical Center Research Institute, was no less impressed. "This is amazing science," Rosen said. "Amazing. The science is spectacular."