title: Effects of parathyroid hormone treatment on circulating sclerostin levels in postmenopausal women.
abstract: BACKGROUND
  Intermittent PTH treatment stimulates bone formation, but the mechanism(s) of this effect remain unclear. Sclerostin is an inhibitor of Wnt signaling, and animal studies have demonstrated that PTH suppresses sclerostin production.
  
  
  OBJECTIVE
  The objective of the study was to test whether intermittent PTH treatment of postmenopausal women alters circulating sclerostin levels.
  
  
  METHODS
  Prospective study.
  
  
  METHODS
  The study was conducted at a clinical research unit.
  
  
  METHODS
  Participants included 27 postmenopausal women treated with PTH (1-34) for 14 d and 28 control women.
  
  
  METHODS
  Serum sclerostin levels were measured.
  
  
  RESULTS
  Circulating sclerostin levels decreased significantly in the PTH-treated subjects, from (mean ± SEM) 551 ± 32 to 482 ± 31 pg/ml (-12.7%, P < 0.0001) but did not change in the control women (baseline, 559 ± 34 pg/ml; end point, 537 ± 40 pg/ml, P = 0.207; P = 0.017 for difference in changes between groups). Bone marrow plasma was obtained in a subset of the control and PTH-treated subjects (n = 19 each) at the end of the treatment period, and marrow plasma and peripheral serum sclerostin levels were significantly correlated (R = 0.64, P < 0.0001). Marrow plasma sclerostin levels were 24% lower in PTH-treated compared with control women, but perhaps due to the smaller sample size, this difference was not statistically significant (P = 0.173).
  
  
  CONCLUSIONS
  Circulating sclerostin levels correlate with bone marrow plasma levels and are reduced by intermittent PTH therapy in postmenopausal women. Further studies are needed to assess the extent to which decreases in sclerostin production contribute to the anabolic skeletal response to PTH.
authors.affiliation: Division of Endocrinology and Metabolism, College of Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA.
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Drake
authors.forename: Bhuma
authors.initials: B
authors.lastname: Srinivasan
authors.forename: Ulrike I
authors.initials: UI
authors.lastname: Mödder
authors.forename: James M
authors.initials: JM
authors.lastname: Peterson
authors.forename: Louise K
authors.initials: LK
authors.lastname: McCready
authors.forename: B Lawrence
authors.initials: BL
authors.lastname: Riggs
authors.forename: Denise
authors.initials: D
authors.lastname: Dwyer
authors.forename: Marina
authors.initials: M
authors.lastname: Stolina
authors.forename: Paul
authors.initials: P
authors.lastname: Kostenuik
authors.forename: Sundeep
authors.initials: S
authors.lastname: Khosla
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000368:Aged; D000369:Aged, 80 and over; D019485:Bone Morphogenetic Proteins / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005819:Genetic Markers; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood; D015663:Osteoporosis, Postmenopausal / Q000097:blood* / Q000188:drug therapy; D010281:Parathyroid Hormone / Q000494:pharmacology* / Q000627:therapeutic use; D017698:Postmenopause / Q000097:blood*; D011446:Prospective Studies; D053245:RANK Ligand / Q000097:blood; D016896:Treatment Outcome
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D019485:Bone Morphogenetic Proteins; C501126:DKK1 protein, human; D005819:Genetic Markers; D036341:Intercellular Signaling Peptides and Proteins; D010281:Parathyroid Hormone; D053245:RANK Ligand; C422903:SOST protein, human; D015675:Osteocalcin