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Inhibiting serotonin in gut could cure osteoporosis
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Using an investigational drug that inhibits serotonin synthesis in the gut cured osteoporosis in post-menopausal rodents, according to an international team led by researchers from Columbia University Medical Center.
The findings appear in the online issue of Nature Medicine.
“New therapies that inhibit the production of serotonin in the gut have the potential to become a novel class of drugs to be added to the therapeutic arsenal against osteoporosis,” Gerard Karsenty, MD, PhD, the lead author of the study and chair of the Department of Genetics and Development at Columbia University College of Physicians and Surgeons, stated in a university press release. “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.”
Orthopedics Today Basic Science & Research Section Editor, Gunnar B.J. Andersson, MD, PhD, told OrthoSuperSite.com that the study was “interesting,” and agreed that these findings could possibly lead to the development of an alternative to current treatments for osteoporosis.
“At some point, clinical trials are needed to confirm positive results in humans,” Andersson said. “Before then, we need to know more about the safety and side effects of this. Serotonin has many other effects outside of bone.” He further indicated that it is too early to speculate on the clinical application of the drug.
According to the release, Karsenty and his colleagues had previously discovered that serotonin released in the gut inhibits bone formation, and that regulating serotonin synthesis in the gut affects the formation of bone. These findings, which were published in Cell, led them to postulate that an inhibitor of serotonin synthesis should be an effective treatment for osteoporosis.
Soon after, they learned of the investigational drug, LP533401, which inhibits serotonin synthesis in the gut. “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,” Karsenty stated in the release.
The team administered a small oral dose of the drug, once a day for up to 6 weeks, to rodents with post-menopausal osteoporosis. Results demonstrated that osteoporosis could be fully cured and that serotonin levels in the brain were unaffected, thereby avoiding many potential side effects, according to the press release.
Most current osteoporosis drugs can only prevent the breakdown of old bone. According to the release, there is one drug on the market can generate new bone. However, it must be taken by injection once a day, and it is restricted for short-term use in women with severe osteoporosis because it has been shown to increase the risk of cancer in rats.
“There is an urgent need to identify new, safe therapies that can increase bone formation on a long term basis and to such an extent that they compensate for the increase in bone resorption caused by menopause,” Karsenty stated in the release. “Furthermore, it is important to note that since this study was conducted in rodents, it will need further confirmation in human subjects.”
- References:
Yadav VK, Balaji S, Suresh PS, et al. Pharmacological inhibition of gut-derived serotonin synthesis is a potential bone anabolic treatment for osteoporosis. Nat Med. 2010 Feb 7. [Epub ahead of print]
