Circulating sclerostin in disorders of parathyroid gland function.

CONTEXT: Sclerostin, a protein encoded by the SOST gene in osteocytes and an antagonist of the Wnt signaling pathway, is down-regulated by PTH administration. Disorders of parathyroid function are useful clinical settings to study this relationship.

OBJECTIVE

The objective of the study was to evaluate sclerostin in two different disorders of parathyroid function, primary hyperparathyroidism and hypoparathyroidism, and to analyze the relationship between sclerostin and PTH, bone markers, and bone mineral density.

DESIGN

This is a cross-sectional study.

SETTING

The study was conducted at a clinical research center.

PATIENTS: Twenty hypoparathyroid and 20 hyperparathyroid patients were studied and compared to a reference control group.

RESULTS

Serum sclerostin was significantly higher in hypoparathyroid subjects than in hyperparathyroid subjects (P < 0.0001) and controls (P < 0.0001). PTH was negatively associated with sclerostin, achieving statistical significance in hypoparathyroidism (r = -0.545; P = 0.02). The bone turnover markers, cross-linked C-telopeptide of type I collagen (CTX) and amino-terminal propeptide of type I collagen (P1NP), were differently associated with sclerostin according to the parathyroid disorder. In primary hyperparathyroidism, bone turnover markers were associated negatively with sclerostin (for P1NP, r = -0.490; P = 0.03). In hypoparathyroidism, bone turnover markers were associated positively with sclerostin (for CTX, r = +0.571; P = 0.01). Although there was no significant correlation between bone mineral density and sclerostin in either parathyroid disorder, there was a significant positive relationship between sclerostin and bone mineral content in hypoparathyroidism.

CONCLUSIONS

The results are consistent with the hypothesis that PTH is a regulator of sclerostin in human disorders of parathyroid function. In addition, the results suggest that bone mineral content may be another factor that influences sclerostin.