Osteoprotegerin and receptor activator of nuclear factor‐κB ligand system in the early post‐operative period of liver transplantation

Abstract

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. 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. 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. 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.