Zdravniški Vestnik (Nov 2007)
OPG/RANKL/RANK cytokine system in renal osteodystrophy
Abstract
Background: Renal osteodystrophy is one of the most common complications affecting patients with endstage renal disease treated with hemodialysis (HD). The action of calciotropic hormones in renal osteodystrophy is regulated by the OPG/RANKL/RANK system. Its function is modulated by interleukines, calcitriol and parathyroid hormone (PTH).The aim of our study was to confirm that this system is involved in the pathogenesis of renal osteodystrophy and supports the mechanism of PTH action on bone.Methods: 106 HD patients (mean age 60 years) and 50 healthy volunteers (mean age 64 years) were enrolled in the study. In serum samples of patients and controls we determined concentrations of OPG, RANKL, tartarat resistant acid phosphatase 5b (TRAP 5b), serum Cterminal telopeptide cross-links of type I collagen (CTx), bone specific alkaline phosphatase (BALP), osteocalcin (OC) and parathyroid hormone (PTH). We compared serum measurements of HD patients and controls and assessed the correlation of OPG and RANKL with bone markers. The most frequent OPG promotor gene polymorphisms were also determined. SPSS 12.1 for Windows was used for statistical analysis.Results: Median OPG concentrations were approximately three times higher in HD patients (0.804 µg/l) than in healthy volunteers (0.272 µg/l). Mean serum RANKL concentrations were 1.66- fold higher in HD patients (1.36 pmol/l) than in controls (0.82 pmol/l). Serum RANKL levels significantly differed between patients with and without calcitriol therapy (p = 0.001). After dividing HD patients into tertiles according to PTH, we observed significantly higher OPG values in the lower and RANKL in the upper tertile (p < 0.001). OPG did not correlate with bone resorption markers. Only weak correlation of bone formation markers with osteocalcin was noted. In contrast to OPG, RANKL correlated well with PTH, OC and CTX. OPG promoter gene polymorphisms (149 T → C, 163 A → G, 950 T → C) do not influence OPG expression and consequently its serum levels.Conclusions: Our results support the outcomes of in vitro studies of PTH inhibitory action on OPG and PTH stimulatory action on RANKL synthesis. The highest OPG values were observed in the first tertile and RANKL levels in the third PTH tertile. In HD patients with high bone turnover, PTH action leads to disbalance in OPG/RANKL/RANK and consequently to accelerated bone resorption. We proved the role of the OPG/RANKL/RANK system in the pathogenesis of renal osteodystrophy.
