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Nat Med. 2010 Mar;16(3):308-12. doi: 10.1038/nm.2098. Epub 2010 Feb 7.

Pharmacological inhibition of gut-derived serotonin synthesis is a potential bone anabolic treatment for osteoporosis.

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  • 1Department of Genetics and Development, Columbia University Medical Center, New York, New York, USA.

Abstract

Osteoporosis is a disease of low bone mass most often caused by an increase in bone resorption that is not sufficiently compensated for by a corresponding increase in bone formation. As gut-derived serotonin (GDS) inhibits bone formation, we asked whether hampering its biosynthesis could treat osteoporosis through an anabolic mechanism (that is, by increasing bone formation). We synthesized and used LP533401, a small molecule inhibitor of tryptophan hydroxylase-1 (Tph-1), the initial enzyme in GDS biosynthesis. Oral administration of this small molecule once daily for up to six weeks acts prophylactically or therapeutically, in a dose-dependent manner, to treat osteoporosis in ovariectomized rodents because of an isolated increase in bone formation. These results provide a proof of principle that inhibiting GDS biosynthesis could become a new anabolic treatment for osteoporosis.

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PMID:
20139991
[PubMed - indexed for MEDLINE]
PMCID:
PMC2836724
Free PMC Article
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