Salivary Cystatin C as a Potential Biomarker in Stage III/IV Periodontitis: A Comparative Study

Aim: Periodontitis is a chronic, multifactorial inflammatory disease characterized by progressive destruction of the supporting periodontal tissues. Early identification of disease activity and severity remains a clinical challenge. Salivary biomarkers offer promise as noninvasive tools for diagnosis and monitoring. Cystatin C, a cysteine protease inhibitor, plays a regulatory role in tissue proteolysis and inflammation, but its salivary expression in advanced periodontal disease remains underexplored. The aim of the study was to quantitatively assess and compare salivary cystatin C levels in periodontally healthy individuals and patients diagnosed with stage III/IV periodontitis and to evaluate its correlation with key clinical parameters. Materials and Methods: This cross-sectional analytical study included 36 participants aged 30–65 years, equally divided into healthy controls ( n = 18) and stage III/IV periodontitis patients ( n = 18), classified per the 2017 World Workshop criteria. Standardized periodontal clinical parameters—plaque index (PI), gingival index (GI), probing pocket depth (PPD), and clinical attachment loss (CAL)—were recorded by a calibrated, blinded examiner. Unstimulated whole saliva samples were collected under controlled conditions and analyzed for cystatin C using a validated enzyme-linked immunosorbent assay (ELISA) protocol. Statistical analysis included independent t tests, Pearson’s correlation, Bonferroni correction, multivariate linear regression, and analysis of covariance (ANCOVA) to adjust for confounders. Results: Salivary cystatin C levels were significantly elevated in the periodontitis group (3.16 ± 0.65 ng/mL) compared to healthy controls (0.78 ± 0.23 ng/mL; P < 0.01). A large effect size (Cohen’s d = 4.88) underscored the clinical relevance of this difference. Cystatin C positively correlated with CAL ( r = 0.685, P = 0.02) and PPD ( r = 0.455, P = 0.05), but not with PI or GI. Age was an independent predictor of cystatin C levels ( β = 0.05, P = 0.02); however, ANCOVA confirmed the intergroup difference remained significant after adjusting for age ( P < 0.01). Conclusion: Salivary cystatin C demonstrates strong potential as a noninvasive biomarker for assessing periodontal disease severity, particularly reflecting deep tissue destruction rather than superficial inflammation. Its significant association with CAL supports its utility in disease monitoring. Larger longitudinal and multi-marker studies are warranted to validate its diagnostic accuracy and establish clinical thresholds.