Salivary Oxidative Stress Biomarkers in Temporomandibular Disorders: A Systematic Review and Meta-Analysis

Background: Temporomandibular disorders (TMD) are multifactorial musculoskeletal conditions frequently associated with chronic pain, inflammation, and functional impairment. Increasing evidence suggests that oxidative stress may contribute to the pathophysiology of TMD, and salivary biomarkers have emerged as a promising non-invasive approach for evaluating these biological alterations. Objective: This systematic review and meta-analysis aimed to systematically evaluate and quantitatively synthesize the available evidence regarding salivary oxidative stress biomarkers in patients with temporomandibular disorders compared with healthy controls. Materials and Methods: A systematic review and meta-analysis were conducted according to PRISMA 2020 guidelines and prospectively registered in PROSPERO. Electronic searches were performed in PubMed/MEDLINE, Embase, Scopus, and Web of Science databases. Observational studies and clinical trials evaluating salivary oxidative stress biomarkers in patients with TMD were included. The primary biomarkers assessed were malondialdehyde (MDA), total antioxidant capacity (TAC), and catalase activity (CAT). Data extraction and risk of bias assessment were independently performed by two reviewers using the Newcastle-Ottawa Scale and RoB 2 tool when applicable. Random-effects meta-analyses were conducted using weighted or standardized mean differences with 95% confidence intervals. Included studies demonstrated substantial methodological variability regarding TMD diagnostic criteria, saliva collection protocols, biomarker assays, and sampling conditions. Results: Pooled analyses showed significantly elevated salivary malondialdehyde levels in patients with TMD compared with healthy controls, suggesting increased lipid peroxidation and oxidative stress activity. In contrast, total antioxidant capacity and catalase activity demonstrated inconsistent and non-significant findings across studies. Considerable heterogeneity was identified among studies, limiting the comparability and interpretability of pooled estimates. Salivary oxidative stress biomarkers, particularly malondialdehyde, appear to be associated with temporomandibular disorders and may reflect underlying oxidative and inflammatory mechanisms. Conclusions: However, substantial methodological heterogeneity and lack of standardized protocols currently limit their clinical applicability. Future well-designed longitudinal studies using harmonized diagnostic and analytical methodologies are required to clarify their translational value in TMD assessment.