Telegraph India
8 February, 2010
G.S Mudur
New Delhi, India

Indian and American scientists have discovered a new medical strategy to combat osteoporosis, raising hopes of a daily pill to prevent and even reverse this chronic disease of bone loss common in post–menopausal women.

The researchers have shown through animal studies that blocking the production of a compound named serotonin in the gut with a synthetic molecule administered orally prevents and even restores bone loss in osteoporosis.

The studies by Vijay Yadav at Columbia University Medical Centre, New York, and his colleagues have shown that a daily dose of the medication can prevent or reverse the osteoporosis – a “proof–of–principle” for a new therapy. Yadav and his colleagues from Columbia, Bangalore, Lucknow, and Harvard University announced their results today in the journal Nature Medicine.

The scientists performed their experiments in mice and rats whose ovaries had been surgically removed. Rats without ovaries make up a good model for post–menopausal women because of similarities in bone loss patterns.

They observed that the anti–serotonin molecule could treat osteoporosis in mice and rats in a dose–dependent manner – the higher the dose, the greater the effect. But the molecule worked even at a small dose of 25 mg per kg body weight.

Serotonin has long been known as a regulator of the biological clock in the brain that responds to day–night cycles. But two years ago, Yadav and his colleagues found that serotonin in the gut prevents bone formation.

The synthetic molecule tested by the Indo–US team blocks gut–serotonin and thus restores bone formation – without any affect on serotonin in the brain and with no adverse effects in the stomach, the scientists have reported.

“The gut seems to control bone mass,” said Rudraiah Medhamurthy, a team member and biologist at the Indian Institute of Science, Bangalore. “This may be an excellent target for manipulating bone mass,” he told The Telegraph.

Most of the drugs currently prescribed for osteoporosis prevent loss of bone and can prevent the progression of the disease, but cannot restore a normal bone mass, Ducy said. A standard current therapy involves injections of parathyroid hormone but it carries safety concerns and is prescribed in severe cases. Studies also suggest that its effect lasts only about two years.

“The oral administration would be a true advantage – both in terms of convenience and compliance,” Patricia Ducy, assistant professor at Columbia University Medical Centre and a senior team member told The Telegraph.

“There is a need for new therapy,” Ducy said. But the scientists caution that the animal studies would need to be followed up through a series of human trials to determine efficacy and safety in humans. Such clinical studies could take two to five years to complete.

Anil Balapure, a biochemist at the Central Drug Research Institute studied the effect of the synthetic molecule on the serotonin–producing cells in the gut, while the studies on rats were performed at the IISc, Bangalore.

Yadav’s moves helped bring the Indian and US teams together. He was a doctoral student at the IISc with Medhamurthy as his guide and had spent time at the CDRI before moving to the US.

While hormonal changes make post–menopausal women prime candidates for osteoporosis – a condition marked by severe bone loss and bones vulnerable to fractures – men may also develop the disease. Doctors estimate that India had about 25 million patients with osteoporosis in 2005, but the number is expected to grow to more than 35 million by 2013.