title: Sclerostin and Dickkopf-1 in renal osteodystrophy.
abstract: OBJECTIVE
  The serum proteins sclerostin and Dickkopf-1 (Dkk-1) are soluble inhibitors of canonical wnt signaling and were recently identified as components of parathyroid hormone (PTH) signal transduction. This study investigated the associations between sclerostin and Dkk-1 with histomorphometric parameters of bone turnover, mineralization, and volume in stage 5 chronic kidney disease patients on dialysis (CKD-5D).
  
  
  METHODS
  In a cross-sectional study, 60 CKD-5D patients underwent bone biopsies followed by histomorphometry. Levels of sclerostin, Dkk-1, and intact PTH (iPTH) were determined in blood.
  
  
  RESULTS
  Serum levels of sclerostin and iPTH correlated negatively. In unadjusted analyses, sclerostin correlated negatively with histomorphometric parameters of turnover, osteoblastic number, and function. In adjusted analyses, sclerostin remained a strong predictor of parameters of bone turnover and osteoblast number. An observed correlation between sclerostin and cancellous bone volume was lost in regression analyses. Sclerostin was superior to iPTH for the positive prediction of high bone turnover and number of osteoblasts. In contrast, iPTH was superior to sclerostin for the negative prediction for high bone turnover and had similar predictive values than sclerostin for the number of osteoblasts. Serum levels of Dkk-1 did not correlate with iPTH or with any histomorphometric parameter.
  
  
  CONCLUSIONS
  Our data describe a promising role for serum measurements of sclerostin in addition to iPTH in the diagnosis of high bone turnover in CKD-5D patients, whereas measurements of Dkk-1 do not seem to be useful for this purpose.
authors.affiliation: Division of Nephrology, Medical University Vienna, Vienna, Austria.
authors.forename: Daniel
authors.initials: D
authors.lastname: Cejka
authors.forename: Johann
authors.initials: J
authors.lastname: Herberth
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Branscum
authors.forename: David W
authors.initials: DW
authors.lastname: Fardo
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Monier-Faugere
authors.forename: Danielle
authors.initials: D
authors.lastname: Diarra
authors.forename: Martin
authors.initials: M
authors.lastname: Haas
authors.forename: Hartmut H
authors.initials: HH
authors.lastname: Malluche
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D019485:Bone Morphogenetic Proteins / Q000097:blood / Q000502:physiology*; D016723:Bone Remodeling; D001862:Bone Resorption; D002113:Calcification, Physiologic; D002908:Chronic Disease; D012080:Chronic Kidney Disease-Mineral and Bone Disorder / Q000209:etiology*; D003430:Cross-Sectional Studies; D005260:Female; D005819:Genetic Markers / Q000502:physiology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood / Q000502:physiology*; D007674:Kidney Diseases / Q000097:blood; D008297:Male; D008875:Middle Aged; D010012:Osteogenesis; D010281:Parathyroid Hormone / Q000097:blood
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; C422903:SOST protein, human