Serum and salivary uric acid levels in oral submucous fibrosis: a systematic review and meta-analysis

This study aimed to evaluate differences in serum uric acid (SeUA) and salivary uric acid (SaUA) levels between patients with oral submucous fibrosis (OSF) and healthy controls. PubMed, Embase, Web of Science, Google Scholar, and the Cochrane Library were searched for studies reporting uric acid (UA) levels in OSF through July 2025, without language restrictions. Study quality was assessed using the Newcastle-Ottawa Scale (NOS) and the Agency for Healthcare Research and Quality (AHRQ) checklist. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were pooled using random-effects models, and heterogeneity was assessed with the I² statistic. Ten studies, all conducted in South Asia, were included. Meta-analysis of nine studies involving 297 OSF patients and 450 healthy controls found no significant overall difference in SeUA levels (SMD = − 0.94, 95% CI: −2.07 to 0.20; P = 0.107), with substantial heterogeneity (I² = 97.5%). Subgroup analyses suggested that this null finding may mask assay-dependent differences. Non-uricase-based assays showed significantly lower SeUA levels in OSF (SMD = − 2.18, P = 0.018), driven primarily by early-stage disease ( P = 0.040). However, although uricase-based assays showed no overall difference, stage-stratified analyses consistently demonstrated significantly higher SeUA levels in both early-stage ( P = 0.013) and advanced-stage OSF ( P < 0.001). Descriptive synthesis of two studies showed consistently reduced SaUA levels in OSF, with a stage-dependent decline. The observed publication bias ( P = 0.010) was attributable to two outlying studies and was no longer evident after their exclusion. Overall, the included studies were of moderate to high quality. UA metabolism in OSF appears to be compartment-specific. SaUA is consistently depleted, potentially reflecting local oxidative exhaustion, whereas uricase-based serum measurements may suggest a tendency toward systemic UA accumulation across both early and advanced disease stages. Previous inconsistencies in the literature may largely reflect the limited analytical specificity of non-uricase assays. Uricase-based SeUA shows potential for monitoring systemic disease progression. While preliminary data suggest SaUA might reflect localized fibrotic activity, current evidence is limited. Future large-cohort studies are required to validate the clinical utility of these potential biomarkers. PROSPERO (CRD420251105127).