title: Circulating sclerostin in disorders of parathyroid gland function.
abstract: BACKGROUND
  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.
  
  
  METHODS
  This is a cross-sectional study.
  
  
  METHODS
  The study was conducted at a clinical research center.
  
  
  METHODS
  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.
authors.affiliation: Department of Medicine, Division of Endocrinology, Metabolic Bone Diseases Unit, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
authors.forename: Aline G
authors.initials: AG
authors.lastname: Costa
authors.forename: Serge
authors.initials: S
authors.lastname: Cremers
authors.forename: Mishaela R
authors.initials: MR
authors.lastname: Rubin
authors.forename: Donald J
authors.initials: DJ
authors.lastname: McMahon
authors.forename: James
authors.initials: J
authors.lastname: Sliney
authors.forename: Marise
authors.initials: M
authors.lastname: Lazaretti-Castro
authors.forename: Shonni J
authors.initials: SJ
authors.lastname: Silverberg
authors.forename: John P
authors.initials: JP
authors.lastname: Bilezikian
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D015519:Bone Density / Q000502:physiology; D019485:Bone Morphogenetic Proteins / Q000097:blood*; D003430:Cross-Sectional Studies; D005260:Female; D005819:Genetic Markers; D006801:Humans; D008297:Male; D008875:Middle Aged; D010279:Parathyroid Diseases / Q000097:blood* / Q000503:physiopathology; D010280:Parathyroid Glands / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D019485:Bone Morphogenetic Proteins; D005819:Genetic Markers; C422903:SOST protein, human