Serotonin May Be a Key to Treat Osteoporosis
Study Shows Experimental Drug May Build New Bone by Decreasing Serotonin Levels in the Gut
WebMD News Archive
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,
Osteoporosis: Closer to a Cure?
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,
"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.