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We thank A Warren, K Vyas, R Wynne, A DeLoose, W Webb, C Wicker III, S Berryhill, and R Shelton for technical assistance and D Hubberd for assistance in the preparation of the manuscript. ""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 http://www.selleckchem.com/products/a-1155463.html 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 http://www.selleck.cn/products/PD-0332991.html 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?pg/mL; 95% confidence interval [CI] 13.7 to 17.2?pg/mL), in whom it was significantly lower than in healthy controls (mean 40.0?pg/mL; 95% CI 36.9 to 42.7?pg/mL; p? http://www.selleckchem.com/products/cb-5083.html 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?=?0.40, p?=?0.008). Mean CTX levels were well within the normal range and did not differ between patients and disease carriers after adjusting for age (p?=?0.22). 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. ? 2011 American Society for Bone and Mineral Research Sclerosteosis is a rare autosomal recessive bone sclerosing dysplasia characterized by generalized osteosclerosis.