title: Sclerostin: recent advances and clinical implications.
abstract: OBJECTIVE
  Discovery of the Wnt signaling pathway and understanding the central role of osteocyte in skeletal homeostasis have been the major advances in skeletal biology over the past decade. Sclerostin, secreted mainly (but not exclusively) by osteocytes, has emerged as a key player in skeletal homeostasis. This review highlights the most relevant recent advances.
  
  
  RESULTS
  Sclerostin by inhibiting Wnt signaling pathway decreases bone formation and osteoblast differentiation and promotes osteoblast apoptosis. Ability to measure serum sclerostin levels better clarified the role of sclerostin in various physiologic and pathologic states. Early clinical trials with antibodies to sclerostin have produced robust increases in bone mineral density, and fracture prevention trials are underway.
  
  
  CONCLUSIONS
  Since the discovery of Wnt signaling pathway and sclerostin's association with high bone mass, there has been a remarkable progress. Clinical trials with fracture endpoints, already underway, should expand osteoanabolic therapeutic horizon in the very near future. Measurement of sclerostin levels in a number of conditions has advanced our knowledge about pathophysiology of skeletal and nonskeletal disorders in an altogether new light.
authors.affiliation: aDivision of Endocrinology, Diabetes, and Bone & Mineral Disorders, Henry Ford Hospital, Detroit, Michigan bSection of Endocrinology, Diabetes and Metabolism, Temple University School of Medicine, Philadelphia, Pennslyvania cBone and Mineral Research Laboratory, Henry Ford Hospital, Detroit, Michigan, USA.
authors.forename: Mahalakshmi
authors.initials: M
authors.lastname: Honasoge
authors.forename: Ajay D
authors.initials: AD
authors.lastname: Rao
authors.forename: Sudhaker D
authors.initials: SD
authors.lastname: Rao
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D015519:Bone Density; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D001842:Bone and Bones / Q000378:metabolism*; D002454:Cell Differentiation; D005819:Genetic Markers; D006801:Humans; D015576:Hyperostosis / Q000378:metabolism* / Q000503:physiopathology; D010006:Osteoblasts; D010009:Osteochondrodysplasias / Q000378:metabolism* / Q000503:physiopathology; D010011:Osteocytes; D010024:Osteoporosis / Q000378:metabolism* / Q000503:physiopathology; D015398:Signal Transduction; D013576:Syndactyly / Q000378:metabolism* / Q000503:physiopathology; D051153:Wnt Proteins / Q000378:metabolism* / Q000502:physiology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D019485:Bone Morphogenetic Proteins; D005819:Genetic Markers; C422903:SOST protein, human; D051153:Wnt Proteins