Circulating sclerostin in children and young adults with heritable bone disorders

Abstract

Context: Sclerostin isaninhibitor ofboneformationandisanimportant determinant ofbonemass. The role of sclerostin in heritable metabolic bone disorders has not been studied in detail. Objective: We evaluated serum sclerostin levels in patients with X-linked hypophosphatemic rickets (XLH) and osteogenesis imperfecta (OI) and analyzed the relationship of circulating sclerostin concentrations with lumbar spine areal bone mineral density (LS-aBMD). Setting: The study was conducted in the metabolic bone clinic of a pediatric orthopedic hospital. Patients: Participants were 128 individuals, including 30 patients with XLH, 76 patients with OI types I, III, and IV, and 22 healthy subjects. Main Outcome Measures: Sclerostin was quantified in serum samples. Results: Patients with XLH had higher circulating sclerostin concentrations (mean [SD]: 30.2 [16.7] pmol/L) than healthy control subjects (21.4 [9.2] ng/mL) (P.02), as well as relatively high LS-aBMD Z-scores (+1.1 [1.7]). In the XLH cohort, serum sclerostin levels were positively associated with the LS-aBMD Z-score (r = 0.56; P < .002) and with alkaline phosphatase (r = 0.45; P = .01). In patients with OI, sclerostin serum levels were similar to those of healthy control subjects despite low LS-aBMD. Conclusions: The elevated sclerostin serum levels in XLH and the normal concentrations in OI suggest that the bone mass abnormalities in these disorders are not caused by primary sclerostin dysregulation. © 2014 by the Endocrine Society.