title: Sclerostin: Another vascular calcification inhibitor?
abstract: BACKGROUND
  Sclerostin, a Wnt antagonist produced by osteocytes, regulates osteoblast activity and is a well-established key player in bone turnover. Recent data indicate that the Wnt pathway may also be involved in vascular calcification.
  
  
  OBJECTIVE
  The present study tests the hypothesis that serum sclerostin levels are associated with vascular calcification in patients with chronic kidney disease (CKD) not yet receiving dialysis.
  
  
  METHODS
  We performed a cross-sectional analysis in 154 patients with CKD. Aortic calcification (AC) was assessed by lumbar X-ray and scored with a maximum score of 24. In addition to traditional and nontraditional cardiovascular (CV) risk factors, serum sclerostin levels were assessed (ELISA). Regression analysis was performed to identify determinants of serum sclerostin and AC.
  
  
  RESULTS
  AC was present in 59% of patients. Older age (P < .0001), male sex (P = .006), lower estimated glomerular rate (eGFR) (P = .0008), lower bone-specific alkaline phosphatase (P = .03), and the absence of AC (P = .006) were identified as independent determinants of higher serum sclerostin levels. In univariate logistic regression, higher age, diabetes, CV history, higher body mass index, higher serum C-reactive protein and sclerostin levels and lower estimated glomerular rate were all associated with the presence of AC. In multivariate analysis, lower, not higher, sclerostin levels (P = .04, odds ratio [OR] per ng/mL of 0.24), higher age (P < .0001, OR per year of 1.17) and CV history (P = .02, OR for a positive CV history of 3.83) were identified as independent determinants of AC.
  
  
  CONCLUSIONS
  In this cohort of patients with CKD, we found that patients with aortic calcifications (ACs) had higher sclerostin levels. However, in multivariate analysis, the association became inverse. Additional clinical and experimental studies are urgently required to clarify whether or not sclerostin protects against progression of vascular calcification.
authors.affiliation: Department of Nephrology, University Hospitals Leuven, Herestraat 49, B-3000 Leuven, Belgium. kathleen.claes@uzleuven.be
authors.forename: Kathleen J
authors.initials: KJ
authors.lastname: Claes
authors.forename: Liesbeth
authors.initials: L
authors.lastname: Viaene
authors.forename: Sam
authors.initials: S
authors.lastname: Heye
authors.forename: Björn
authors.initials: B
authors.lastname: Meijers
authors.forename: Patrick
authors.initials: P
authors.lastname: d'Haese
authors.forename: Pieter
authors.initials: P
authors.lastname: Evenepoel
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D001018:Aortic Diseases / Q000097:blood / Q000209:etiology*; D019485:Bone Morphogenetic Proteins / Q000097:blood* / Q000502:physiology; D003430:Cross-Sectional Studies; D005260:Female; D005819:Genetic Markers / Q000502:physiology; D005919:Glomerular Filtration Rate; D006801:Humans; D008297:Male; D008875:Middle Aged; D051436:Renal Insufficiency, Chronic / Q000097:blood*; D061205:Vascular Calcification / Q000097:blood / Q000209:etiology*; D051153:Wnt Proteins / Q000037:antagonists & inhibitors*; D060449:Wnt Signaling Pathway / Q000502:physiology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D019485:Bone Morphogenetic Proteins; D005819:Genetic Markers; C422903:SOST protein, human; D051153:Wnt Proteins