Context: Sclerostin is an inhibitor of bone formation and is an important determinant of bone mass. 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.