Drug explored that taken once daily could cure osteoporosis
Loss of bone mass from osteoporosis that increases fracture risk and occurs with aging is a major health concern. With an aging population at high risk for osteoporosis, a new drug is being explored that could cure osteoporosis, and has done exactly that in mice and rats when administered once a day. The drug works by inhibiting serotonin production in the gut.
Researchers investigating the osteoporosis drug from Columbia University Medical Center say that serotonin in the gut has been found in recent studies to slow down formation of new bone growth, leading to exploration of a new class of drugs. Gerard Karsenty, M.D., Ph.D., chair of the Department of Genetics and Development at Columbia University College of Physicians and Surgeons who lead the study says, "With tens of millions of people worldwide affected by this devastating and debilitating bone loss, there is an urgent need for new treatments that not only stop bone loss, but also build new bone. Using these findings, we are working hard to develop this type of treatment for human patients." Osteoporosis affects women primarily, but can also affect men.
Serotonin is found in the brain and acts as a neurotransmitter that regulates mood. Ninety five percent of serotonin is in the gut where one of its functions is to inhibit bone formation. Researchers found that inhibiting the release of serotonin in the gut cured osteoporosis in mice whose ovaries were removed to simulate menopause.
Following the above findings, the research team discovered the investigational drug LP533401. "When we learned of this compound, we thought that it was important to test it as proof of principle that there could be novel ways to treat osteoporosis with therapies that can be taken orally and regulate the formation of serotonin," said Dr. Karsenty.
When they gave rodents the drug once a day for up to six weeks and in small doses, they found that LP533401 cured osteoporosis associated with menopause, as well as preventing bone loss. Notably, serotonin levels in the brain were unaffected, meaning the drug prevented and cured osteoporosis and would be unlikely to have major side effects. The drug was developed to treat irritable bowel syndrome in humans, tested at high doses.
With aging, bone mass declines. Menopause accelerates the rate of bone loss and increases the risk of osteoporosis. Only one drug on the market prevents bone loss, and it is given by way of injection once a month. The side effects include bone cancer, and it is only given in severe cases of osteoporosis. The development of safe drugs to prevent and cure osteoporosis by allowing new bone formation has widespread implications for improving quality of life with aging.
In the meantime, calcium and vitamin D, combined with regular weight bearing exercises are the best known ways to prevent osteoporosis. For individuals with osteoporosis, exercise can slow the rate of bone loss and should be guided by a physician to prevent fractures. Studies are needed to confirm the same results found in mouse studies showing that LP533401 given once a day could also cure osteoporosis in humans.
Nature Medicine: doi:10.1038/nm.2098