title: Sclerostin: therapeutic horizons based upon its actions.
abstract: Inactivating mutations of the SOST gene cause a reduction in sclerostin levels and are associated with high bone mass. The clinical phenotypes, sclerosteosis and van Buchem's disease, were described in 1950s. Much later, it was learned that both diseases are due to loss-of-function mutations in the SOST gene. As a regulator of an important osteoanabolic pathway, Wnt, inactivation of SOST leads to a stimulation of the pathway it regulates. The high bone mass in patients with either sclerosteosis or van Buchem's disease is associated with unusual skeletal strength; they do not fracture. Knowledge of this molecule and its actions led rather quickly to the development of anti-sclerostin antibodies that lead to marked increases in bone mass in both animals and human subjects. Blocking sclerostin action with anti-sclerostin antibodies is a promising new therapeutic approach to osteoanabolic therapy of osteoporosis.
authors.affiliation: Department of Medicine, Division of Endocrinology, Metabolic Bone Diseases Unit, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
authors.forename: Aline G
authors.initials: AG
authors.lastname: Costa
authors.forename: John P
authors.initials: JP
authors.lastname: Bilezikian
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D001842:Bone and Bones / Q000378:metabolism*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005819:Genetic Markers; D006801:Humans; D015576:Hyperostosis / Q000188:drug therapy* / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D010026:Osteosclerosis / Q000188:drug therapy* / Q000503:physiopathology; D060449:Wnt Signaling Pathway / Q000187:drug effects* / Q000502:physiology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000911:Antibodies, Monoclonal; D019485:Bone Morphogenetic Proteins; D005819:Genetic Markers; C422903:SOST protein, human; C557282:romosozumab