Circulating Sclerostin in Disorders of Parathyroid Gland Function

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Costa, Aline G. [UNIFESP]
Cremers, Serge
Rubin, Mishaela R.
McMahon, Donald J.
Sliney, James
Lazaretti-Castro, Marise [UNIFESP]
Silverberg, Shonni J.
Bilezikian, John P.
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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. (J Clin Endocrinol Metab 96: 3804-3810, 2011)
Journal of Clinical Endocrinology & Metabolism. Chevy Chase: Endocrine Soc, v. 96, n. 12, p. 3804-3810, 2011.