title: Osteoprotegerin and receptor activator of nuclear factor-kappaB ligand system in the early post-operative period of liver transplantation.
abstract: BACKGROUND
  The precise mechanism that leads to accelerated bone resorption in the early post-transplant period remains unclear. Recent data suggest that osteoprotegerin (OPG) and its ligand receptor activator of nuclear factor-kappaB ligand (RANKL) constitute a novel cytokine system that can influence the function of both bone and immune cells. The aim of our study was to assess OPG and RANKL concentrations in the early post-operative period of liver transplantation.
  
  
  METHODS
  Serum OPG and RANKL levels were measured in 30 patients who underwent liver transplantation at 1, 7 and 14 d post-operatively. These values were compared with 22 age- and sex-matched healthy controls. Plasma sodium, creatinine, aspartate-aminotransferase, alanine-amino transferase, gamma-glutamyl transferase, alkaline phosphatase, bilirubin, albumin, prothrombin time, tacrolimus and cyclosporine levels were measured in each patient.
  
  
  RESULTS
  We found a significant increase in OPG levels in the early post-operative period compared with the control group: day 1 (10.42 pmol/L, range 3.80-17.50 vs. 3.91 pmol/L, range 1.20-6.60; p = 0.0001), day 7 (6.90 pmol/L, range 3.00-15.30 vs. 3.91 pmol/L, range 1.20-6.60; p = 0.0001) and day 14 (5.76 pmol/L, range 2.60-10.70 vs. 3.91 pmol/L, range 1.20-6.60; p = 0.001). Similarly, serum RANKL levels were significantly higher than in the control group in this period, day 1 (0.123 pmol/L, range 0.010-0.420 vs. 0.054 pmol/L, range 0.010-0.300; p = 0.02), day 7 (0.236 pmol/L, range 0.010-0.720 vs. 0.054 pmol/L, range 0.010-0.300; p = 0.0004) and day 14 (0.137 pmol/L, range 0.010-0.520 vs. 0.054 pmol/L, range 0.010-0.300; p = 0.007). No correlation was found between OPG levels and RANKL, ischemic times, liver function tests, albumin, sodium or creatinine concentrations and tacrolimus or cyclosporine levels.
  
  
  CONCLUSIONS
  A significant amount of OPG and RANKL is released in the early post-transplant period of liver transplantation. This might be explained by an activation of the immune system caused by the allograft. Therefore, the RANKL/OPG system may be involved in the pathophysiological evolution of transplantation osteoporosis.
authors.affiliation: Gastroenterology and Hepatology Unit, University Hospital Marqués de Valdecilla, Faculty of Medicine, UC Santander, Spain.
authors.forename: Emilio
authors.initials: E
authors.lastname: Fábrega
authors.forename: Aitor
authors.initials: A
authors.lastname: Orive
authors.forename: Maite
authors.initials: M
authors.lastname: García-Unzueta
authors.forename: Jose Antonio
authors.initials: JA
authors.lastname: Amado
authors.forename: Fernanado
authors.initials: F
authors.lastname: Casafont
authors.forename: Fernando
authors.initials: F
authors.lastname: Pons-Romero
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002352:Carrier Proteins / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D008111:Liver Function Tests; D016031:Liver Transplantation; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008875:Middle Aged; D053244:Osteoprotegerin; D011184:Postoperative Period; D011379:Prognosis; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D002352:Carrier Proteins; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human