Multi-Element Salivary Biomarker Profiling for Non-Invasive Stratification of Periodontal Disease

Electrolyte–Trace Element Interactions and Diagnostic Performance

Abstract

This study aimed to evaluate salivary sodium, potassium, cobalt, and iron as a multi-element biomarker profile for non-invasive stratification of periodontal disease and to investigate electrolyte–trace element interactions in relation to periodontal inflammatory and structural parameters. This comparative cross-sectional study included 90 adults equally classified into periodontally healthy, gingivitis, and periodontitis groups. Unstimulated whole saliva samples were collected using the passive drool method, and salivary sodium, potassium, cobalt, and iron concentrations were measured by atomic absorption spectrophotometry. Clinical periodontal parameters included bleeding on probing (BOP), probing pocket depth (PPD), and clinical attachment level (CAL). Group comparisons, post-hoc testing, correlation analysis, inter-element correlation analysis, and receiver operating characteristic (ROC) curve analysis were performed. Salivary sodium increased progressively from periodontal health to gingivitis and periodontitis (16.64 ± 2.33, 20.50 ± 2.55, and 22.39 ± 3.23 mmol/L, respectively; p < 0.001), whereas potassium decreased across the corresponding groups (12.36 ± 1.32, 10.65 ± 1.77, and 10.38 ± 2.30 mmol/L, respectively; p < 0.001). Cobalt and iron were also reduced in disease groups compared with healthy controls, decreasing from 0.28 ± 0.09 to 0.21 ± 0.09 and 0.18 ± 0.09 µg/dL for cobalt, and from 47.63 ± 11.03 to 34.40 ± 8.89 and 30.77 ± 11.35 µg/dL for iron, respectively (both p < 0.001). Sodium showed the clearest progressive discriminatory pattern across the three periodontal groups, while potassium, cobalt, and iron mainly distinguished periodontal health from disease. Sodium was positively correlated with BOP (r = 0.565, p < 0.001), whereas potassium (r = -0.316, p = 0.002), cobalt (r = -0.314, p = 0.003), and iron (r = -0.468, p < 0.001) were negatively correlated with BOP. None of the salivary elements showed significant correlations with PPD or CAL within the periodontitis group. Inter-element analysis showed that sodium and potassium, cobalt, and iron were all negatively correlated whereas potassium, cobalt, and iron were positively correlated with each other. ROC analysis showed the best diagnostic performance for sodium, with the most significant difference between healthy controls and periodontitis noted (AUC = 0.932, sensitivity = 83.3%, specificity = 86.7%). Periodontal disease was correlated with a coordinated multi-element salivary profile characterized by elevated sodium levels and concurrent reductions in potassium, cobalt, and iron. This elemental remodeling pattern was more related to periodontal inflammatory burden rather than structural periodontal destruction. Multi-element salivary biomarker profiling may serve as a promising non-invasive adjunct for periodontal disease stratification, although further validation in larger and demographically balanced cohorts is required.