Salivary Oxidative Stress and Cortisol Biomarkers in Tem-poromandibular Disorders and Oral Lichen Planus: A System-atic Review and Meta-Analysis

Background: Saliva has emerged as a promising non-invasive biological fluid for monitoring systemic and local alterations associated with oral diseases. Oxidative stress biomarkers and stress-related hormones have been increasingly investigated in temporomandibular disorders (TMD) and oral lichen planus (OLP), yet findings remain heterogeneous. Objective: This study aimed to systematically evaluate and quantitatively synthesize differences in salivary oxidative stress biomarkers and cortisol levels between patients with TMD or OLP and healthy controls. Methods: A systematic review and meta-analysis was conducted according to PRISMA 2020 guidelines and registered in PROSPERO (CRD420250654690). Electronic databases (MEDLINE, PubMed, EMBASE, Web of Science, and Scopus) were searched for studies published in the last 10 years assessing salivary biomarkers in TMD and OLP. Observational studies and clinical trials reporting quantitative biomarker levels were included. Pooled weighted mean differences (WMDs) were calculated using random-effects models. Heterogeneity was assessed using the I² statistic. Results: A total of twelve studies were included in the quantitative synthesis, evaluating salivary biomarkers in temporomandibular disorders (TMD) and oral lichen planus (OLP). In TMD patients, salivary malondialdehyde (MDA) levels were significantly higher compared to controls, indicating increased oxidative stress. Total antioxidant capacity (TAC) and catalase activity (CAT) showed inconsistent and non-significant differences across studies. In OLP patients, pooled analysis demonstrated significantly elevated salivary cortisol levels compared with healthy individuals, suggesting an association between psychological stress and disease presence. However, substantial heterogeneity was observed (I² = 98.9%), likely reflecting methodological differences in saliva collection, assay techniques, and population characteristics. Conclusions: Salivary biomarkers, particularly MDA in TMD and cortisol in OLP, are associated with disease status and may serve as complementary indicators of oxidative and psychological burden. Nevertheless, high heterogeneity and variability in study protocols limit definitive clinical application. Standardized methodologies and well-designed longitudinal studies are required to clarify their translational potential.