The main cytokines regulating bone remodeling are the receptor activator of nuclear factor-κB ligand (RANKL) and its decoy receptor, osteoprotegerin (OPG). Recent data have linked RANKL and OPG to cardiovascular disease as well. NT-pro-BNP and adiponectin are well-established biomarkers of heart failure reflecting neuroendocrine activation in this multi-complex disorder. The objective of this article was to investigate whether RANKL is associated with neuroendocrine activation in 75 elderly males with mild to moderate congestive heart failure (CHF) and left ventricular ejection fraction <40%. The control group consisted of 20 healthy male volunteers with matching age and body mass index (BMI). Serum RANKL (sRANKL), OPG, NT-pro-BNP, adiponectin, leptin, clinical, and echocardiography parameters were evaluated. In comparison to the control group, the CHF patients showed significantly increased sRANKL levels [126.8 (122.6) vs. 47.8 (44.4) pg/ml, P < 0.0001]. There was a significant relative risk of systolic CHF in elderly males associated with increased sRANKL above the calculated cut-off of 83 pg/ml [OR = 10.286 (95%CI 3.079-34.356), P < 0.0001; RR = 3.600 (95%CI = 1.482-8.747)]. In the CHF patients, the log-transformed values of sRANKL levels correlated positively with the log-transformed values of the serum NT-pro-BNP and adiponectin levels (P = 0.004, r = 0.326 and P = 0.037, r = 0. 241, respectively), while inversely correlated with the BMI and creatinine clearance (P = 0.015, r = -0.281 and P = 0.042, r = -0.236, respectively). In multivariate regression model, sRANKL was a significant determinant of NT-pro-BNP independent of age, BMI and creatinine clearance (P = 0.002, R (2) = 0.546). In conclusion, our study suggests that in elderly males with systolic heart failure sRANKL was significantly associated with parameters of neuroendocrine activation such as NT-pro-BNP and adiponectin. Further studies are needed to elucidate the potential role of sRANKL in the complex pathogenesis of heart failure.
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