Anti-sclerostin - is there an indication?

Injury
Sune Larsson

Abstract

Several decades ago, a clinical condition that included severe bone overgrowth was described in a few patients in South Africa. The autosomal-recessive disease that later was named sclerosteosis was found to be caused by a mutation in the SOTS gene causing a lack of the protein sclerostin. This protein is produced by osteocytes and exerts its effect as an inhibitor of bone formation by blocking the Wnt signaling pathway. By the use of a monoclonal antibody that can block sclerostin a novel therapeutic pathway for rebuilding bone has been described. Preclinical studies have shown increased bone mass following subcutaneously administered anti-sclerostin antibody in animals with induced postmenopausal osteoporosis as well as in intact male rats and non-human primates. In a phase II study the efficacy and safety of an anti-sclerostin antibody, romosozumab, has been evaluated in 419 postmenopausal women for 12 months. 70, 140 or 210 mg was given subcutaneously monthly or every three months and compared to 70 mg of oral alendronate given once a week or 20 μg of teriparatide subcutaneously once daily. All dose levels of romosozumab were associated with significant increase in BMD with the most pronounced gain in the group receiving 21...Continue Reading

References

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Citations

Mar 28, 2017·Bone·Bart O Williams
Jun 26, 2017·Journal of Bone and Mineral Metabolism·Mohammad M AlzahraniReggie C Hamdy
Feb 14, 2018·Journal of the American Heart Association·Isabella AlbaneseAdel Schwertani
Jan 8, 2017·Arteriosclerosis, Thrombosis, and Vascular Biology·Smriti Murali KrishnaJonathan Golledge
Jan 1, 2016·Terapevticheskiĭ arkhiv·T A GrebennikovaG A Melnichenko
Sep 6, 2018·Nature Reviews. Endocrinology·Natasha M Appelman-Dijkstra, Socrates E Papapoulos

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