Exploring oxidative and antioxidant biomarkers in temporomandibular joint disorders: An exploratory systematic review across multiple biological fluids

Objectives To determine if oxidative stress markers are consistently altered in TMD patients compared to healthy controls, by synthesizing evidence from blood, saliva, and synovial fluid analyses and assessing study quality. Methods Following PRISMA guidelines, Medline/PubMed, Scopus, Web of Science, Google Scholar, Cochrane and Embase were systematically searched for English articles up to September 2025 using MeSH and free keywords. Human observational and clinical studies comparing biomarkers in TMD patients and healthy controls in blood, saliva, and synovial fluid were included. Risk of bias was assessed by using the Newcastle–Ottawa Scale (NOS) Results Fourteen studies were included in the final analysis. Methodological quality was moderate to high (average NOS score 7.07 ± 1.07), with low risk-of-bias studies. Serum-based analyses most consistently showed higher oxidant markers (e.g., MDA) and reduced antioxidants (e.g., SOD) in TMD patients. Saliva results were the most varied. Conclusion This ‘compensatory-to-depletion’ transition may represent a key biochemical indicator for disease staging. Evidence consistently links TMDs with oxidative stress imbalance across sample types, characterized by elevated oxidants (e.g., MDA) correlating with pain severity. Although heterogeneity limits causal inference, serum oxidative markers show diagnostic promise in early-stage/chronic pain states, with a biphasic antioxidant response reflecting progression. PROSPERO Reg CRD420251186118