title: Acute decline in serum sclerostin in response to PTH infusion in healthy men.
abstract: BACKGROUND
  Animal models suggest that the osteoblast-stimulating actions of PTH are mediated by acute suppression of sclerostin, an inhibitor of the anabolic Wnt pathway. The immediate physiological changes in serum sclerostin in response to PTH infusion have not been reported in human studies.
  
  
  OBJECTIVE
  We sought to determine the acute physiological effects of PTH infusion on serum sclerostin and bone turnover markers in healthy adult men.
  
  
  METHODS
  Fifty-three healthy adult men underwent an 18-h iv infusion of human PTH(1-34) at a dose of 0.55 U/kg · h.
  
  
  RESULTS
  Serum levels of ionized calcium, sclerostin, and markers of bone formation (osteocalcin and amino-terminal propeptide of type I procollagen) and bone resorption (C-telopeptide and N-telopeptide) were obtained at 0, 6, 12, and 18 h.
  
  
  RESULTS
  Serum ionized calcium, C-telopeptide, and N-telopeptide increased, and osteocalcin and amino-terminal propeptide of type I procollagen fell linearly throughout the PTH infusion (P < 0.001 for all). Average ± sem sclerostin levels declined from 936 ± 65 to 813 ± 63 pg/ml at 6 h (P < 0.001) and remained stably suppressed for the duration of the PTH infusion. There were no significant correlations between change in sclerostin and change in bone markers.
  
  
  CONCLUSIONS
  Serum sclerostin declined in response to acute PTH infusion within 6 h in healthy adult men. The early plateau in sclerostin suppression may indicate that maximal stimulation of the Wnt pathway is achieved quickly after exposure to PTH. Our findings support the hypothesis that PTH may mediate its anabolic effects in part via suppression of sclerostin.
authors.affiliation: Massachusetts General Hospital Endocrine Unit, 50 Blossom Street, Thier 1051, Boston, Massachusetts 02114, USA. ewyu@partners.org
authors.forename: Elaine W
authors.initials: EW
authors.lastname: Yu
authors.forename: Ruchit
authors.initials: R
authors.lastname: Kumbhani
authors.forename: Erica
authors.initials: E
authors.lastname: Siwila-Sackman
authors.forename: Benjamin Z
authors.initials: BZ
authors.lastname: Leder
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D019485:Bone Morphogenetic Proteins / Q000097:blood*; D016723:Bone Remodeling / Q000187:drug effects*; D002118:Calcium / Q000097:blood; D024042:Collagen Type I / Q000097:blood; D005819:Genetic Markers; D006801:Humans; D008297:Male; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010446:Peptide Fragments / Q000097:blood; D010455:Peptides / Q000097:blood; D011347:Procollagen / Q000097:blood
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D019485:Bone Morphogenetic Proteins; D024042:Collagen Type I; D005819:Genetic Markers; D010281:Parathyroid Hormone; D010446:Peptide Fragments; D010455:Peptides; D011347:Procollagen; C422903:SOST protein, human; C052929:collagen type I trimeric cross-linked peptide; C047202:procollagen Type I N-terminal peptide; D015675:Osteocalcin; D002118:Calcium