Osteoprotegerin and RANKL Serum Levels and Their Relationship with Serum Ghrelin in Children with Chronic Renal Failure and on Dialysis

Abstract

BACKGROUND: Osteoprotegerin (OPG) and receptor activator of the nuclear factor kappaB ligand (RANKL) constitute a complex system of mediators involved in the regulation of bone resorption process. Ghrelin, a growth hormone secretagogue, has been shown to modulate proliferation and differentiation of osteoblasts. The present study was carried out to evaluate the serum concentrations of OPG and sRANKL in children with chronic renal impairment (CRI) and on dialysis, and to establish a possible relationship between their serum levels and that of ghrelin. METHODS: 33 patients including 10 patients with CRI, 12 peritoneal dialysis (PD) and 11 hemodialysis (HD) patients and 22 healthy controls were enrolled into the study. OPG, sRANKL and ghrelin levels were studied with radioimmunoassay. RESULTS: Serum OPG levels in CRI, PD and HD groups were significantly higher than the healthy controls (p = 0.002, p < 0.001, p < 0.001, respectively) whereas sRANKL levels were significantly lower than the healthy controls (p = 0.03, p = 0.01, p = 0.001, respectively). Ghrelin levels were significantly higher in CRI, PD and HD groups compared to healthy controls (p = 0.001, p < 0.001, p < 0.001, respectively). We observed a negative correlation between the sRANKL and OPG levels (r = -0.27, p = 0.04) as well as between sRANKL and ghrelin levels (r = -0.31, p = 0.02). OPG levels showed a positive correlation with ghrelin levels (r = 0.63, p < 0.001). CONCLUSION: We found a lower RANKL bioactivity index in children with CRI and on dialysis. The mechanism and the role of elevated OPG and low sRANKL in uremia are unclear, but they might partly represent a compensatory mechanism to the negative balance of bone remodeling in renal bone disease in children. Additionally, we demonstrated for the first time that ghrelin and the RANKL/OPG system have a close relationship in CRF. Therefore, ghrelin may be of importance in mediating the effects of the RANKL/OPG system in renal bone disease.