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Drug Found to Inhibit, Reverse Osteoporosis in Rodents

Investigational drug blocks gut-derived serotonin synthesis and promotes bone formation

MONDAY, Feb. 8 (HealthDay News) -- An investigational drug that blocks the synthesis of serotonin in the gut prevents and reverses osteoporosis in a rodent model of the disease by promoting bone formation, according to a study published online Feb. 7 in Nature Medicine.

Following up on previous results showing that gut-derived serotonin inhibits osteoblast proliferation and bone formation, Vijay K. Yadav, Ph.D., from the Columbia University Medical Center in New York City, and colleagues tested whether LP533401, an investigational small molecule inhibitor of gut-derived serotonin synthesis, could treat osteoporosis in ovariectomized rodents.

The researchers found that once-daily oral treatment with a relatively small dose of LP533401 for up to six weeks could both prevent osteoporosis and fully rescue established osteoporosis by increasing bone formation. LP533401 reduced serum serotonin levels by 80 percent but had no effect on brain serotonin levels. LP533401 was as effective as high doses of parathyroid hormone, the current treatment standard, although parathyroid hormone was more efficient in long bones and LP533401 was more efficient in vertebrae.

"That this small molecule is taken orally, promotes only bone formation and, for the purpose of treating osteoporosis, is needed at a relatively small dose and only once daily, suggest that inhibitors of gut-derived serotonin synthesis have the potential to become a novel class of bone anabolic drugs to be added to the therapeutic arsenal against osteoporosis," Yadav and colleagues conclude.

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