Osteoprotegerin (OPG) and receptor activator of NF-kB ligand (RANK-L) serum levels in patients on chronic hemodialysis

Abstract

The mechanisms underlying the skeletal resistance to PTH in patients on chronic hemodialysis (CHD) are not yet fully clarified. Osteoprotegerin (OPG) and receptor activator of NF-kB ligand (RANK-L) modulate the genesis and activity of osteoclasts, however their role in renal osteodystrophy pathogenesis has not been clarified so far. The present study aimed to evaluate OPG and RANK-L serum levels in hemodialysis patients and whether OPG/RANK-L system could have a role in the skeletal resistance to PTH. In fasting blood samples obtained from 60 patients (36 males and 24 females) on CHD for at least 2 yr and from 40 healthy subjects of similar age and gender distribution as controls (CTRs), we measured serum OPG, RANK-L, bone alkaline phosphatase (B-ALP), N-terminal telopeptide of type I collagen (NTx), PTH(1-84), calcium and phosphate. In 30 of 60 hemodialysis patients, a blood sample was also drawn soon after the dialytic session. Serum levels of RANK-L, but not OPG, showed a slight but significant (p<0.05) decrease after the dialytic session. OPG resulted being about six times higher in CHD patients than in CTRs (38.7 +/- 16.2 vs 6.3 +/- 0.17 pg/ml), whereas RAN K-L serum levels were only slightly increased with respect to controls (0.88 +/- 0.47 vs 0.64 +/- 0.38 pmol/l). CHD patients showed serum PTH(1-84) and bone turnover higher than in CTRs. No correlation was found between OPG/RANK-L system and PTH or bone turnover markers. Instead, in the patients with high osteoclast activity (no.=21) OPG/RANK-L ratio was correlated (r=-0.41, p<0.01) with NTx serum levels, whereas in patients with decreased osteoclast activity (no.=39) no relationship was found. In conclusion, our findings showed that, although both OPG and RANK-L are accumulated in hemodialysis patients, only RANK-L and the balance between OPG and RANK-L seem to be related to osteoclast activity.

Osteoprotegerin as a Predictor of Coronary Artery Disease and Cardiovascular Mortality and Morbidity

“…OPG levels are significantly higher in patients with chronic kidney disease compared with age-and sex-matched controls, and increasing OPG levels have a linear relationship with worsening renal function (96). Similar findings are noted in patients with chronic kidney disease on hemodialysis (97). In the study by Nitta et al (98), 102 patients on regular hemodialysis were assessed for aortic calcification by a noncontrast computed tomography scan.…”

Lactoferrin Knockout Mice Demonstrates Greater Susceptibility to Aggregatibacter actinomycetemcomitans–Induced Periodontal Disease

“…The higher level expression of RANKL and cathepsin‐K in LFKO −/− I mice was associated with the active state of bone resorption compared to WTI mice. Additionally, the levels of OPG, which prevents the activation of NF‐κB, were inversely proportional to those of RANKL 7,47 . It has also been reported that higher levels of RANKL mRNA in experimental periodontitis lead to bone resorption 7 .…”

Elevated Serum Bone Morphogenetic Protein 4 in Patients with Chronic Kidney Disease and Coronary Artery Disease

“…Serum levels of both OPG and RANKL are elevated in hemodialysis patients and have been investigated as potential biomarkers of CAD in patients with stage 4 and 5 CKD [25–27]. Elevated serum OPG levels correlate with increased coronary artery calcification and mortality [8, 25, 26].…”