title: Serum sclerostin: the missing link in the bone-vessel cross-talk in hemodialysis patients?
abstract: We found for the first time that in maintenance hemodialysis patients, higher sclerostin serum level was associated with severe abdominal aortic calcification (AAC). In addition, cortical bone microarchitecture (density and thickness) assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT) at tibia was also independently associated with severe AAC. These results suggest that sclerostin may be involved in the association of mineral and bone disorder with vascular calcification in hemodialysis patients.
  
  
  BACKGROUND
  Severe abdominal aortic calcifications are predictive of high cardiovascular mortality in maintenance hemodialysis (MHD) patients. In patients with end-stage renal disease, a high aortic calcification score was associated with lower bone turnover on bone biopsies. Thus, we hypothesized that sclerostin, a Wnt pathway inhibitor mainly secreted by osteocytes and acting on osteoblasts to reduce bone formation, may be associated with vascular calcifications in MHD patients.
  
  
  METHODS
  Fifty-three MHD patients, aged 53 years [35-63] (median [Q1-Q3]) were included. Serum was sampled before the MHD session to assay sclerostin. Framingham score was computed and the abdominal aortic calcification (AAC) score was assessed according to Kauppila method on lateral spine imaging using DEXA. Tibia bone status was evaluated by high-resolution peripheral quantitative computed tomography (HR-pQCT). Patients were distributed into two groups according to their AAC score: patients with mild or without AAC (score below 6) versus patients with severe AAC (score of 6 and above).
  
  
  RESULTS
  In multivariate analysis, after adjustment on age, dialysis duration and diabetes, serum sclerostin and cortical thickness were independently associated with severe AAC (odds ratio (OR) = 1.43 for each 0.1 ng/mL increase [95 % confidence interval (CI) 1.10-1.83]; p = 0.006 and 0.16 for 1 SD increase [0.03-0.73]; p = 0.018, respectively). A second cardiovascular model adjusted on Framingham score and the above mentioned confounders showed similar results.
  
  
  CONCLUSIONS
  Elevated sclerostin serum level and poorer tibia cortical bone structure by HR-pQCT were positively and independently associated with higher odds of severe AAC in MHD patients. Serum sclerostin may become a biomarker of mineral and bone disorder and vascular risk in MHD patients.
authors.affiliation: Département de Néphrologie - Bâtiment 3C, Centre Hospitalier Lyon Sud, 69495, Pierre Bénite, France, Solenne.pelletier@chu-lyon.fr.
authors.forename: S
authors.initials: S
authors.lastname: Pelletier
authors.forename: C B
authors.initials: CB
authors.lastname: Confavreux
authors.forename: J
authors.initials: J
authors.lastname: Haesebaert
authors.forename: F
authors.initials: F
authors.lastname: Guebre-Egziabher
authors.forename: J
authors.initials: J
authors.lastname: Bacchetta
authors.forename: M-C
authors.initials: MC
authors.lastname: Carlier
authors.forename: L
authors.initials: L
authors.lastname: Chardon
authors.forename: M
authors.initials: M
authors.lastname: Laville
authors.forename: R
authors.initials: R
authors.lastname: Chapurlat
authors.forename: G M
authors.initials: GM
authors.lastname: London
authors.forename: M-H
authors.initials: MH
authors.lastname: Lafage-Proust
authors.forename: D
authors.initials: D
authors.lastname: Fouque
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001012:Aorta, Abdominal; D001018:Aortic Diseases / Q000097:blood* / Q000209:etiology; D015415:Biomarkers / Q000097:blood; D015519:Bone Density / Q000502:physiology; D019485:Bone Morphogenetic Proteins / Q000097:blood* / Q000502:physiology; D005260:Female; D005819:Genetic Markers / Q000502:physiology; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000150:complications / Q000628:therapy; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis / Q000009:adverse effects*; D013977:Tibia / Q000000981:diagnostic imaging / Q000503:physiopathology; D014057:Tomography, X-Ray Computed / Q000379:methods; D061205:Vascular Calcification / Q000097:blood* / Q000209:etiology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015415:Biomarkers; D019485:Bone Morphogenetic Proteins; D005819:Genetic Markers; C422903:SOST protein, human