Evaluation of Osteoprotegerin (OPG) and Receptor Activator of Nuclear Factor Kappa‐B Ligand (RANKL) Biomarker Concentrations in the Saliva of Patients with Periodontitis and Depression

ABSTRACT Background and Objectives Periodontitis is a chronic inflammatory disease affecting tooth‐supporting structures, while depression is a common mental disorder with emotional and behavioral disturbances. Previous studies suggest a potential association between the two conditions. This study aimed to evaluate salivary concentrations of Receptor Activator of Nuclear Factor Kappa‐B Ligand (RANKL) and Osteoprotegerin (OPG)—key regulators of osteoclast activity and periodontal bone resorption—in patients with periodontitis and depression. Materials and Methods In this cross‐sectional study, 80 patients from Shahid Beheshti University Dental School were categorized into four groups based on the presence or absence of periodontitis and depression. Periodontitis was defined as having ≥ 2 teeth in ≥ 2 quadrants with bleeding on probing, pocket depth > 3 mm, and interdental clinical attachment loss ≥ 1 mm. Depression was assessed using the Persian PHQ‐9, and individuals meeting criteria for major depressive disorder(MDD) were classified as depressed. Unstimulated saliva samples (1 mL) were collected, stored at −20°C, and analyzed for OPG and RANKL using ELISA kits. Statistical analyses included two‐way ANOVA (SPSS v27; p < 0.05 significant). Results Among 80 participants (43 females, 37 males; mean age 45.3 years), RANKL, OPG, and the RANKL/OPG ratio were higher in depressed individuals, but differences were not statistically significant ( p > 0.05). RANKL levels and the RANKL/OPG ratio were significantly higher in patients with periodontitis and increased with disease severity ( p ≤ 0.05), while OPG showed no significant change. Conclusion Periodontitis and its severity significantly influence salivary RANKL and the RANKL/OPG ratio, while depression does not. Within the limits of this cross‐sectional design, no evidence was found that RANKL and OPG act as intermediary biomarkers linking depression and periodontitis.