The Prognostic Reliability of Inflammatory Biomarkers in Temporomandibular Joint Disorder – A Systematic Review

Abstract Background: Temporomandibular disorders (TMDs) are complex, multifactorial conditions involving the temporomandibular joint (TMJ) and associated musculoskeletal structures, often characterised by inflammatory involvement. Inflammatory mediators play a key role in symptom severity, disease progression and treatment response. This systematic review aims to synthesise current evidence on the prognostic value of inflammatory biomarkers in TMDs. Objectives: To evaluate the prognostic reliability of inflammatory biomarkers measured in TMJ synovial fluid for predicting treatment response and disease progression in adults with TMDs. Data Sources & Study Eligibility Criteria: A systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses 2020 guidelines. Participants & Interventions: Electronic searches were performed in PubMed, PubMed Central, Scopus, ScienceDirect, the Cochrane Library and Google Scholar for studies published between 2013 and 2023. Randomised controlled trials and clinical trials assessing inflammatory biomarkers in TMJ synovial fluid were included. Study Appraisal & Synthesis Methods: Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Due to methodological and clinical heterogeneity, a narrative synthesis was performed. Results: Five studies met the inclusion criteria. Elevated levels of interleukin-1β (IL1β), IL6 and tumour necrosis factor-alpha (TNF-α) were consistently associated with disease severity and treatment response across studies, although effect sizes varied according to intervention type. Limitations & Conclusions: Inflammatory biomarkers, particularly IL1β, IL6 and TNFα, demonstrate potential prognostic value in TMDs. However, heterogeneity among studies limits quantitative pooling, highlighting the need for standardised biomarker methodologies.