Depressive Symptoms and RANKL/OPG in Hemodialysis

Background: Depression and osteoporosis are prevalent in dialysis patients. Denosumab and romosozumab similarly block RANKL. While RANKL causes bone resorption after binding RANKL, binding with OPG inhibits bone resorption. A recent mice study, denosumab improved depressive-like phenotype by inhibiting RANKL. OPG was linked to depression. This study aimed to explore the association of depressive symptoms with RANKL/OPG in HD patients. Methods: We conducted a cross-sectional study involving 172 HD patients, measuring plasma RANKL, OPG levels. Logistic regression analysis was performed to evaluate the effect of RANKL and OPG on the depressive symptoms. Results: Thedepressive symptoms were observed in 90(52.3%) subjects. RANKL tertile 3 had negative association with BDI score(β-4.527, 95% CI -8.310~-0.743) in univariate analysis. This association persisted after multivariate adjustments(β-5.603, 95% CI -9.715~-1.491) in linear regression. In logistic regression between RANKL tertiles and depressive symptoms, RANKL tertile 3 had significantly lower unadjusted OR (0.40, 95% CI 0.19~0.86), and multivariate-adjusted OR (0.31, 95% CI 0.12~0.82) for depressive symptoms. Conclusion: OPG wasn't significantly associated with depressive symptoms. Higher plasma RANKL levels were associated with lower depressive symptoms in HD patients.Odds ratios of plasma RANKL, OPG, and RANKL/OPG ratio for depressive symptoms - OR (95% CI)Unadjusted P value OR (95% CI)Adjusted P Value RANKL tertile 1 Reference Reference RANKL tertile 2 0.51 (0.24-1.09) 0.080 0.42 (0.16-1.09) 0.074 RANKL tertile 3 0.40 (0.19-0.86) 0.018 0.31 (0.12-0.82) 0.018 OPG tertile 1 Reference Reference OPG tertile 2 1.64 (0.78-3.44) 0.191 0.59 (0.20-1.69) 0.326 OPG tertile 3 1.37 (0.66-2.85) 0.401 0.29 (0.08-1.02) 0.165 RANKL/OPG tertile 1 Reference Reference RANKL/OPG tertile 2 0.48 (0.23-1.03) 0.059 0.51 (0.20-1.32) 0.041 RANKL/OPG tertile 3 0.35 (0.17-0.75) 0.007 0.55 (0.21-1.42) 0.256 RANKL receptor activator of nuclear factor-κB ligand, OPG Osteoprotegerin, OR Odds Ratio, CI Confidential Interval Multivariate, adjusted for age, sex, BMI, Diabetes mellitus, cardiovascular diseases, HD vintage, spKt/V, hsCRP