title: Osteoprotegerin and sclerostin in chronic kidney disease prior to dialysis: potential partners in vascular calcifications.
abstract: BACKGROUND
  Osteoprotegerin (OPG), sclerostin and DKK1 constitute opposite bone turnover inhibitors, OPG inhibiting osteoclastogenesis while sclerostin and DKK1 exerting their inhibitory effects on osteoblastogenesis. Both proteins have been recognized as strong risk factors of vascular calcifications in non-dialysis chronic kidney disease (ND-CKD) patients. The aim of this study was to investigate the relationships between these inhibitors and coronary artery calcifications (CAC) in this population.
  
  
  METHODS
  A total of 241 ND-CKD patients [143 males; 69.0 (25.0-95.0) years; median estimated glomerular filtration rate using CKD-EPI 35.1 (6.7-120.1) mL/min/1.73 m(2)] were enrolled in this cross-sectional study. All underwent chest multidetector computed tomography for CAC scoring. OPG, sclerostin, DKK1 and mineral metabolism markers including PTH and bone alkaline phosphatase were measured. Logistic regression analyses were used to study the relationships between CAC and these markers.
  
  
  RESULTS
  Decline in renal function was associated with a significant increase in OPG and sclerostin while a slight but significant decrease in DKK1 was observed. The main crude associations with presence of CAC were a high level of OPG [OR = 2.55 95% confidence interval (95% CI) (1.35-4.82) for a level ranging from 6.26 to 9.15 pmol/L and OR = 5.74 95% CI (2.87-11.5) for a level ≥9.15 pmol/L; P < 0.0001] and a high level of sclerostin [OR = 2.64 95% CI (1.39-5.00) for a level ranging from 0.748 to 1.139 ng/mL and OR = 3.78 95% CI (1.96-7.31) for a level ≥1.139 ng/mL; P = 0.0002]. A logistic regression model clearly showed that the risk to present CAC was significantly increased when both OPG (≥6.26 pmol/L) and sclerostin (≥0.748 ng/mL) levels were high [crude model: OR = 11.47 95% CI (4.54-29.0); P < 0.0001; model adjusted for age, gender, diabetes, body mass index and smoking habits: OR = 5.69 95% CI (1.76-18.4); P = 0.02]. No association between DKK1 and presence of CAC was observed.
  
  
  CONCLUSIONS
  Our results strongly suggest that bone turnover inhibitors, OPG and sclerostin, are independently associated with CAC with potential additive effects in ND-CKD patients.
authors: Laboratoire de Biochimie, CHRU de Montpellier, Montpellier, France Institut de Recherche et de Formation en Dialyse, Montpellier, France U1046 INSERM, UMR9214 CNRS, Université de Montpellier, Montpellier, France.
authors: Marion
authors: M
authors: Morena
authors: U1061 INSERM, Montpellier, France Université de Montpellier, Montpellier, France.
authors: Isabelle
authors: I
authors: Jaussent
authors: Laboratoire de Biochimie, CHRU de Montpellier, Montpellier, France.
authors: Anne-Marie
authors: AM
authors: Dupuy
authors: Laboratoire de Biochimie, CHRU de Montpellier, Montpellier, France U1046 INSERM, UMR9214 CNRS, Université de Montpellier, Montpellier, France.
authors: Anne-Sophie
authors: AS
authors: Bargnoux
authors: Laboratoire de Biochimie, CHRU de Montpellier, Montpellier, France U1046 INSERM, UMR9214 CNRS, Université de Montpellier, Montpellier, France.
authors: Nils
authors: N
authors: Kuster
authors: Service de Néphrologie, CHRU de Montpellier, Montpellier, France.
authors: Leila
authors: L
authors: Chenine
authors: Service de Néphrologie, CHRU de Montpellier, Montpellier, France.
authors: Hélène
authors: H
authors: Leray-Moragues
authors: U1046 INSERM, UMR9214 CNRS, Université de Montpellier, Montpellier, France Service de Réanimation Métabolique, CHRU de Montpellier, Montpellier, France.
authors: Kada
authors: K
authors: Klouche
authors: Service de Radiologie, CHRU de Montpellier, Montpellier, France.
authors: Hélène
authors: H
authors: Vernhet
authors: Institut de Recherche et de Formation en Dialyse, Montpellier, France Université de Montpellier, Néphrologie, Montpellier, France Fresenius Medical Care, Bad Homburg, Germany.
authors: Bernard
authors: B
authors: Canaud
authors: Laboratoire de Biochimie, CHRU de Montpellier, Montpellier, France Institut de Recherche et de Formation en Dialyse, Montpellier, France U1046 INSERM, UMR9214 CNRS, Université de Montpellier, Montpellier, France.
authors: Jean-Paul
authors: JP
authors: Cristol
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood*; D019485:Bone Morphogenetic Proteins / Q000097:blood*; D016723:Bone Remodeling / Q000187:drug effects; D003324:Coronary Artery Disease / Q000097:blood* / Q000209:etiology; D003430:Cross-Sectional Studies; D005260:Female; D005819:Genetic Markers; D005919:Glomerular Filtration Rate; D006801:Humans; D008297:Male; D008875:Middle Aged; D053244:Osteoprotegerin / Q000097:blood*; D006435:Renal Dialysis / Q000009:adverse effects*; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000209:etiology; D012307:Risk Factors; D061205:Vascular Calcification / Q000097:blood* / Q000209:etiology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015415:Biomarkers; D019485:Bone Morphogenetic Proteins; D005819:Genetic Markers; D053244:Osteoprotegerin; C422903:SOST protein, human; C506030:TNFRSF11B protein, human
keywords: CAC; DKK1; OPG; SOST; chronic kidney disease