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Its use to decrease bone fragility in pediatric OI has shown efficacy in several growing mouse models, suggesting translational potential to pediatric disorders of low bone mass. However, the effects of pharmacologic inhibition of sclerostin during periods of rapid growth and development have not yet been described with respect to the cranium, where lifelong deficiency of functioning sclerostin leads to patterns of excessive bone growth, cranial compression, and facial palsy. In the present study, we undertook dimensional and volumetric measurements in the skulls of growing Brtl\/+ OI mice treated with Scl-Ab to examine whether therapy-induced phenotypic changes were similar to those observed clinically in patients with sclerosteosis or Van Buchem disorder. Mice treated between 3 and 14\u2009weeks of age with high doses of Scl-Ab show significant calvarial thickening capable of rescuing OI-induced deficiencies in skull thickness. Other changes in cranial morphology, such as lengths and distances between anatomic landmarks, intracranial volume, and suture interdigitation, showed minimal effects of Scl-Ab when compared with growth-induced differences over the treatment duration. Treatment-induced narrowing of foramina was limited to sites of vascular but not neural passage, suggesting patterns of local regulation. Together, these findings reveal a site specificity of Scl-Ab action in the calvaria with no measurable cranial nerve impingement or brainstem compression. This differentiation from the observed outcomes of lifelong sclerostin deficiency complements reports of Scl-Ab treatment efficacy at other skeletal sites with the prospect of minimal cranial secondary complications. \u00a9 2019 American Society for Bone and Mineral Research. \u00a9 2019 American Society for Bone and Mineral Research.<\/jats:p>","DOI":"10.1002\/jbmr.3858","type":"journal-article","created":{"date-parts":[[2019,8,23]],"date-time":"2019-08-23T15:34:34Z","timestamp":1566574474000},"page":"2301-2310","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Sclerostin Antibody\u2013Induced Changes in Bone Mass Are Site Specific in Developing Crania"],"prefix":"10.1093","volume":"34","author":[{"given":"Amanda L","family":"Scheiber","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering University of Michigan Ann Arbor MI USA"},{"name":"Department of Orthopaedic Surgery University of Michigan Ann Arbor MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David K","family":"Barton","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering University of Michigan Ann Arbor MI USA"},{"name":"Department of Orthopaedic Surgery University of Michigan Ann Arbor MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Basma M","family":"Khoury","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery University of Michigan Ann Arbor MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joan C","family":"Marini","sequence":"additional","affiliation":[{"name":"Bone and Extracellular Matrix Branch National Institute of Child Health and Human Disorders, NIH Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald L","family":"Swiderski","sequence":"additional","affiliation":[{"name":"Kresge Hearing Research Institute University of Michigan Ann Arbor MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle S","family":"Caird","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery University of Michigan Ann Arbor MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1108-7258","authenticated-orcid":false,"given":"Kenneth M","family":"Kozloff","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering University of Michigan Ann Arbor MI USA"},{"name":"Department of Orthopaedic Surgery University of Michigan Ann Arbor MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,8,23]]},"reference":[{"key":"2024021014410130300_jbmr3858-bib-0001","doi-asserted-by":"crossref","first-page":"17052","DOI":"10.1038\/nrdp.2017.52","article-title":"Osteogenesis imperfecta","volume":"3","author":"Marini","year":"2017","journal-title":"Nat Rev Dis 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