{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T09:46:39Z","timestamp":1789897599244,"version":"4.0.1"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2011,7,22]],"date-time":"2011-07-22T00:00:00Z","timestamp":1311292800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Sclerosteosis is a rare bone sclerosing dysplasia, caused by loss-of-function mutations in the SOST gene, encoding sclerostin, a negative regulator of bone formation. The purpose of this study was to determine how the lack of sclerostin affects bone turnover in patients with sclerosteosis and to assess whether sclerostin synthesis is decreased in carriers of the SOST mutation and, if so, to what extent this would affect their phenotype and bone formation. We measured sclerostin, procollagen type 1 amino-terminal propeptide (P1NP), and cross-linked C-telopeptide (CTX) in serum of 19 patients with sclerosteosis, 26 heterozygous carriers of the C69T SOST mutation, and 77 healthy controls. Chips of compact bone discarded during routine surgery were also examined from 6 patients and 4 controls. Sclerostin was undetectable in serum of patients but was measurable in all carriers (mean 15.5\u2009pg\/mL; 95% confidence interval [CI] 13.7 to 17.2\u2009pg\/mL), in whom it was significantly lower than in healthy controls (mean 40.0\u2009pg\/mL; 95% CI 36.9 to 42.7\u2009pg\/mL; p\u2009&amp;lt;\u20090.001). P1NP levels were highest in patients (mean 153.7\u2009ng\/mL; 95% CI 100.5 to 206.9\u2009ng\/mL; p\u2009=\u20090.01 versus carriers, p\u2009=\u20090.002 versus controls), but carriers also had significantly higher P1NP levels (mean 58.3\u2009ng\/mL; 95% CI 47.0 to 69.6\u2009ng\/mL) than controls (mean 37.8\u2009ng\/mL; 95% CI 34.9 to 42.0\u2009ng\/mL; p\u2009=\u20090.006). In patients and carriers, P1NP levels declined with age, reaching a plateau after the age of 20 years. Serum sclerostin and P1NP were negatively correlated in carriers and age- and gender-matched controls (r\u2009=\u20090.40, p\u2009=\u20090.008). Mean CTX levels were well within the normal range and did not differ between patients and disease carriers after adjusting for age (p\u2009=\u20090.22). Our results provide in vivo evidence of increased bone formation caused by the absence or decreased synthesis of sclerostin in humans. They also suggest that inhibition of sclerostin can be titrated because the decreased sclerostin levels in disease carriers did not lead to any of the symptoms or complications of the disease but had a positive effect on bone mass. Further studies are needed to clarify the role of sclerostin on bone resorption. \u00a9 2011 American Society for Bone and Mineral Research<\/jats:p>","DOI":"10.1002\/jbmr.474","type":"journal-article","created":{"date-parts":[[2011,7,24]],"date-time":"2011-07-24T07:02:10Z","timestamp":1311490930000},"page":"2804-2811","source":"Crossref","is-referenced-by-count":119,"title":["Patients with sclerosteosis and disease carriers: Human models of the effect of sclerostin on bone turnover"],"prefix":"10.1093","volume":"26","author":[{"given":"Antoon H","family":"van Lierop","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neveen AT","family":"Hamdy","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herman","family":"Hamersma","sequence":"additional","affiliation":[{"name":"Flora Clinic, Roodenpoort, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rutger L","family":"van Bezooijen","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon","family":"Power","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Orthopedic Research Unit, University of Cambridge, Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nigel","family":"Loveridge","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Orthopedic Research Unit, University of Cambridge, Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Socrates E","family":"Papapoulos","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2011,7,22]]},"reference":[{"key":"2024020804160325300_bib1","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1007\/s00223-010-9372-1","article-title":"Sclerostin: current knowledge and future perspectives","volume":"87","author":"Moester","year":"2010","journal-title":"Calcif Tissue Int."},{"key":"2024020804160325300_bib2","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1093\/hmg\/10.5.537","article-title":"Increased bone density in sclerosteosis is due to the deficiency of a novel secreted protein (SOST)","volume":"10","author":"Balemans","year":"2001","journal-title":"Hum Mol Genet."},{"key":"2024020804160325300_bib3","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1086\/318811","article-title":"Bone dysplasia sclerosteosis results from loss of the SOST gene product, a novel cystine knot-containing protein","volume":"68","author":"Brunkow","year":"2001","journal-title":"Am J Hum Genet."},{"key":"2024020804160325300_bib4","doi-asserted-by":"crossref","first-page":"E1526","DOI":"10.1002\/humu.21274","article-title":"First missense mutation in the SOST gene causing sclerosteosis by loss of sclerostin function","volume":"31","author":"Piters","year":"2010","journal-title":"Hum Mutat."},{"key":"2024020804160325300_bib5","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1084\/jem.20031454","article-title":"Sclerostin is an osteocyte-expressed negative regulator of bone formation, but not a classical BMP antagonist","volume":"199","author":"van Bezooijen","year":"2004","journal-title":"J Exp Med."},{"key":"2024020804160325300_bib6","doi-asserted-by":"crossref","first-page":"19883","DOI":"10.1074\/jbc.M413274200","article-title":"Sclerostin binds to LRP5\/6 and antagonizes canonical Wnt signaling","volume":"280","author":"Li","year":"2005","journal-title":"J Biol Chem."},{"key":"2024020804160325300_bib7","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1359\/jbmr.061002","article-title":"Wnt but not BMP signaling is involved in the inhibitory action of sclerostin on BMP-stimulated bone formation","volume":"22","author":"van Bezooijen","year":"2007","journal-title":"J Bone Miner Res."},{"key":"2024020804160325300_bib8","first-page":"209","article-title":"Osteopetrosis with syndactyly; 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