WebMD Health News
Louise Chang, MD
Feb. 7, 2010 -- The hormone serotonin may hold the key to new treatments for reversing osteoporosis-related bone loss, new research finds.
When investigators at Columbia University Medical Center treated mice and rats with an experimental drug that stopped the gut from synthesizing serotonin, they were able to reverse severe bone loss and essentially cure osteoporosis in the animals.
The same team made headlines a little over a year ago with the discovery that bone formation is inhibited by serotonin in the gut. Serotonin is best known for its effects in the brain on mood.
Their latest finding, reported Feb. 7 in the journal Nature Medicine, holds the promise of new and better treatments for building new bone, osteoporosis experts tell WebMD.
Most bone treatments work to block bone loss and make existing bone stronger. One drug, Forteo, does build new bone, but it requires daily injections and is limited to two years of use.
"The notion of a different approach to producing new bone is very, very exciting," National Osteoporosis Foundation past president Ethel S. Siris, MD, tells WebMD.
While serotonin is widely thought of as a brain chemical, as much as 95% of the serotonin in the body is found not in the brain, but in the gut.
The finding that gut serotonin inhibits bone formation led the Columbia researchers to speculate that inhibiting serotonin synthesis could be an effective treatment for osteoporosis, Columbia's Gerard Karsenty, MD, PhD, tells WebMD.
"By pure serendipity, we came across an experimental drug that did just that," he says.
The oral drug, known as LP533401, was developed for the treatment of irritable bowel syndrome (IBS) and it has been tested in humans at high doses, he says.
Karsenty says even at these doses, little toxicity was reported and, most importantly, the drug did not cross the blood-brain barrier and interfere with serotonin's ability to stabilize mood.
The Columbia team's first investigation confirmed that the drug did decrease circulating levels of serotonin in the gut without affecting serotonin levels in the brains of mice and rats.
They then showed that treatment could prevent osteoporosis in female rodents whose ovaries had been surgically removed to mimic menopause.
In another round of studies, they confirmed that treatment could reverse severe bone loss and build new bone in the animals. And in a final round they compared its efficacy to injected parathyroid hormone, finding that it worked as well to build new bone at lower doses.
Karsenty says more research in small animals will be needed to determine the risks and benefits of longer treatment and to identify different compounds that may work even better than the one tested.
He would not speculate on when studies in larger animals and humans might get under way.
"We have to go fast, slowly," he says. "This is promising, but we have a lot more research to do."
Siris, who directs Columbia's Toni Stabile Research Center, says a drug that builds bone and can be taken orally would represent a big advance in the treatment of osteoporosis.
"This is a devastating disease and it is very expensive," she says. "We pay $20 billion a year in this country to fix fractures. One in two women and one in four men will break a bone as they age."
National Osteoporosis Foundation President Robert R. Recker, MD, of Creighton University, tells WebMD that the research is promising but still preliminary.
"This work is interesting, but it is not yet overwhelming," he says.
SOURCES:Yadav, V.K., Nature Medicine, published online Feb. 7, 2010.Gerard Karsenty, MD, PhD, chairman, department of genetics and development,
Columbia University College of Physicians and Surgeons, New York.Ethel S. Siris, MD, director, Toni Stabile Osteoporosis Center, Columbia
University Medical Center, New York.Robert R. Recker, MD, MACP, FACE, professor of medicine and director,
Osteoporosis Research Center, Creighton University School of Medicine, Omaha,
Neb.News release, Columbia University.
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