Serotonin could reverse osteoporosis

7th February 2010 - The hormone serotonin may hold the key to new treatments for reversing osteoporosis related bone loss, new research has found.

When investigators treated mice and rats with an experimental drug that stopped the gut from synthesising serotonin, they were able to reverse severe bone loss and essentially cure osteoporosis in the animals.

The same team from the medical centre at Columbia University in the US made headlines just 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 findings, reported in the journal Nature Medicine, hold the promise of new and better treatments for building new bone, osteoporosis experts believe.

Most bone treatments work to block bone loss and make existing bone stronger. One drug, teriparatide, does build new bone, but it requires daily injections and is limited to 18 months of use in the UK.

The idea of a different approach to producing new bone, by taking a tablet, would be a big step forward in the treatment of osteoporosis.

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 researchers to speculate that inhibiting serotonin synthesis could be an effective treatment for osteoporosis, the Columbia University’s Dr Gerard Karsenty tells us.

"By pure serendipity, we came across an experimental drug that did just that," he says.

The oral medicine, 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.

Dr 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 stabilise mood.

The study 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. 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.

A lot more research before human trials begin

Dr 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."

A drug that builds bone and can be taken orally would represent a big advance in the treatment of osteoporosis.

Around three million people in the UK have osteoporosis. The NHS treats more than 230,000 fractures linked to osteoporosis every year.

Click here to find out more about osteoporosis.