Editors' ChoiceBone biology/Bone health

Building Better Bones

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Science Translational Medicine  03 Mar 2010:
Vol. 2, Issue 21, pp. 21ec33
DOI: 10.1126/scitranslmed.3000998

Bone is constantly being remodeled, which is why every 10 years our skeletons have been completely replaced. This constant remodeling allows us to maintain and adapt bone strength and is also critical for the maintenance of calcium homeostasis. If the balance between bone-forming osteoblasts and bone-resorbing osteoclasts is impaired, it can result in an increase in bone mass or in a weakening of bone, called osteoporosis. As our societies age, the prevalence of osteoporosis is increasing with substantial public health consequences. Clinicians treat osteoporosis mostly with bisphosphonates, which are antiresorptive drugs that can be taken as pills. What is missing is a pill that acts as a bone-rebuilding or anabolic agent. The only currently available anabolic drug is parathyroid hormone (PTH), a drug that needs to be injected and is quite expensive. Yadav et al. show that an anabolic drug that could be taken orally may be in reach.

In a prior study, Yadav et al. had shown that gut-derived serotonin inhibits bone formation. In the gut, serotonin is synthesized by tryptophan hydroxylase-1 (Tph-1), whereas in the brain, where serotonin functions as a neurotransmitter, it is synthesized by Tph-2. Yadav et al. used a small-molecule inhibitor of Tph-1 to suppress serotonin biosynthesis, which improved osteoporosis in several rodent models by increasing bone formation. Although there is a third anabolic bone drug on the horizon, a neutralizing antibody against the secreted protein sclerostin that inhibits bone formation, this again would have to be injected, whereas the Tph-1 inhibitor can be taken orally. Thus, this study is a proof of principle that Tph-1 inhibition is an anabolic treatment for osteoporosis and provides further insight into the complex biology of serotonin.

V. K. Yadav et al., Pharmacological inhibition of gut-derived serotonin synthesis is a potential bone anabolic treatment for osteoporosis. Nat. Med. 7 February 2010 (doi: 10.1038/nm.2098). [Abstract]

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