title: Sclerostin quo vadis? - is this a useful long-term mortality parameter in prevalent hemodialysis patients?
abstract: OBJECTIVE
  Cardiovascular calcification contributes to the increased mortality in hemodialysis patients. Sclerostin was identified as an antianabolic bone factor causing soft tissue calcification. Data on prospective large-scale studies associating sclerostin with mortality in hemodialysis patients are so far inconsistent.
  
  
  METHODS
  In our multicenter prospective longitudinal study following hemodialysis patients, we assessed the associations of sclerostin and bone remodeling markers with long-term mortality. We evaluated the relationship between circulating sclerostin, Fibroblast growth factor 23 (FGF23) and traditional bone remodeling markers. Sclerostin levels in hemodialysis patients were compared with healthy controls.
  
  
  RESULTS
  We enrolled 239 hemodialysis patients with a median follow up of 1461 days. In Cox regression analysis, FGF23 (HR 1.40;95%CI 1.11-1.76), parathyroid hormone (PTH) (HR 1.80;95%CI 1.44-2.26) and alkaline phosphatase (AP) (HR 1.50;95%CI 1.10-2.04) per SD, 25(OH)vitamin D (HR 0.42;95%CI 0.23-0.76) per natural log but not sclerostin (HR 1.02;95%CI 0.75-1.38) per SD increase were associated with mortality. FGF23, PTH and AP were negatively associated with sclerostin. Among control and hemodialysis females, sclerostin levels were lower than in men.
  
  
  CONCLUSIONS
  Higher FGF23, PTH, AP and lower 25(OH)vitamin D but not sclerostin predict long-term mortality. Sclerostin was negatively associated with FGF23, PTH and AP and lower in females than in males.
authors.affiliation: Department of Internal Medicine, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Albina
authors.initials: A
authors.lastname: Nowak
authors.forename: Ferruh
authors.initials: F
authors.lastname: Artunc
authors.forename: Andreas L
authors.initials: AL
authors.lastname: Serra
authors.forename: Emily
authors.initials: E
authors.lastname: Pollock
authors.forename: Pierre-Alexandre
authors.initials: PA
authors.lastname: Krayenbühl
authors.forename: Christian
authors.initials: C
authors.lastname: Müller
authors.forename: Björn
authors.initials: B
authors.lastname: Friedrich
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D000469:Alkaline Phosphatase / Q000097:blood; D015415:Biomarkers; D019485:Bone Morphogenetic Proteins / Q000097:blood*; D016723:Bone Remodeling; D015331:Cohort Studies; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000032:analysis; D005500:Follow-Up Studies; D005819:Genetic Markers; D006801:Humans; D006887:Hydroxycholecalciferols / Q000097:blood; D007676:Kidney Failure, Chronic / Q000097:blood / Q000401:mortality*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood; D011237:Predictive Value of Tests; D015995:Prevalence; D011446:Prospective Studies; D006435:Renal Dialysis / Q000401:mortality*; D016896:Treatment Outcome
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015415:Biomarkers; D019485:Bone Morphogenetic Proteins; C000717427:FGF23 protein, human; D005819:Genetic Markers; D006887:Hydroxycholecalciferols; D010281:Parathyroid Hormone; C422903:SOST protein, human; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D000469:Alkaline Phosphatase