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Sclerostin, a Wnt antagonist, acts as a negative regulator of bone formation. Sclerostin antibody (Scl\u2010Ab)\u2013mediated blockade of sclerostin can dramatically enhance bone formation and reduce bone resorption. This study was designed to investigate the therapeutic effect of the Scl\u2010Ab on severe bone loss induced by concurrent mechanical unloading and estrogen deficiency in a hindlimb\u2010suspended and ovariectomized rat model, and to study the cellular mechanisms underlying severe osteoporosis and Scl\u2010Ab action. Unloading and ovariectomy resulted in severe loss of trabecular and cortical bone mass and strength; Scl\u2010Ab can significantly counteract the deterioration of bone in unloaded and\/or ovariectomized rats, with noticeably increased cortical bone formation. Scanning electron microscopy analysis revealed that unloading and ovariectomy lead to multiple morphological and structural abnormalities of osteocytes in cortical bone and the abnormalities were abolished by Scl\u2010Ab administration. This study extends our previous conclusion that Scl\u2010Ab represents a promising therapeutic approach for severe bone loss that occurs after being exposed to estrogen deficiency and prolonged mechanical unloading.<\/jats:p>","DOI":"10.1111\/nyas.13991","type":"journal-article","created":{"date-parts":[[2019,1,15]],"date-time":"2019-01-15T09:40:47Z","timestamp":1547545247000},"page":"91-103","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Retention of osteocytic micromorphology by sclerostin antibody in a concurrent ovariectomy and functional disuse model"],"prefix":"10.1111","volume":"1442","author":[{"given":"Dongye","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering Stony Brook University  Stony Brook New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana","family":"Miranda","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Stony Brook University  Stony Brook New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Stony Brook University  Stony Brook New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangmeng","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Stony Brook University  Stony Brook New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yueli","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Stony Brook University  Stony Brook New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy","family":"Rojas","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Stony Brook University  Stony Brook New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan","family":"He","sequence":"additional","affiliation":[{"name":"Department of Materials Science and Chemical Engineering Stony Brook University  Stony Brook New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minyi","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Stony Brook University  Stony Brook New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liangjun","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Stony Brook University  Stony Brook New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaodong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Metabolic Disorders Amgen, Inc.  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