Serum Sclerostin and Its Association with Bone Turnover Marker in Metabolic Bone Diseases

Sclerostin is a secreted inhibitor of Wnt/beta-catenin signaling that is mainly produced by osteocytes and is an important regulator of bone remodeling. Some studies have evaluated serum sclerostin levels in metabolic bone diseases, but the results have been contradictory. The profile of serum sclerostin levels in patients with osteogenesis imperfecta (OI), X-linked hypophosphatemia (XLH), and Paget's disease of bone (PDB) was obtained to determine their association with bone turnover marker. Serum sclerostin levels, biochemical parameters, and the bone turnover marker, beta-CrossLaps of type 1 collagen containing cross-linked C-telopeptide (beta-CTX), were measured in 278 individuals, comprising 71 patients with OI, 51 patients with XLH, 17 patients with PDB, and 139 age- and sex-matched healthy controls. A correlation analysis was performed between sclerostin and beta-CTX concentration. The univariate logistic regression analysis was used to analyze factors associated with OI, XLH, and PDB. Patients with PDB (11 male 6 female), aged 44.47 +/- 14.75 years; XLH (17 male, 34 female), aged 19.29 +/- 15.65 years; and OI (43 male, 28 female), aged 19.57 +/- 16.45 years, had higher sclerostin level than age- and sex-matched healthy controls [median(interquartile range): 291.60 (153.42, 357.35) vs. 38.00 (27.06, 68.52) pmol/L, 163.40 (125.10, 238.20) vs. 31.13 (20.37, 45.84) pmol/L, and 130.50 (96.12, 160.80) vs. 119.00 (98.89, 194.80) pmol/L, respectively; P < 0.001]. Patients with PDB had the highest level of serum sclerostin, followed by those with XLH and OI (P < 0.05). Sclerostin was positively correlated with beta-CTX in OI and XLH (r=0.541 and r=0.661, respectively; P < 0.001). Higher beta-CTX and sclerostin levels were associated with a higher risk of OI, XLH, and PBD. Sclerostin may be a biomarker of OI, XLH, and PDB. Whether sclerostin inhibitors can be used in these patients requires further analysis using additional cohorts.