Immunonutritional biomarkers in osteoarthritis: mechanistic insights and prognostic potential.

Osteoarthritis (OA) is the most prevalent degenerative joint disease worldwide. Beyond structural injury to cartilage, synovium, and subchondral bone, OA is increasingly recognized as an immunometabolic disorder characterized by low-grade inflammation and dysregulated innate and adaptive immune responses. Nutritional biomarkers-derived from macro- and micronutrient status and metabolite signatures-can shape the OA inflammatory microenvironment by modulating macrophage polarization, T-cell subset balance, cytokine networks, and key signaling programs (e.g., NF-kappaB, JAK/STAT, NLRP3 inflammasome, and oxidative stress pathways), thereby influencing tissue catabolism and pain sensitization. This review reorganizes the literature around how clinically measurable nutritional biomarkers map onto immune-cell programs and core OA pathological processes, and critically appraises evidence strength and translational readiness. Most biomarker-OA links are supported primarily by mechanistic rationale and observational associations, while longitudinal and interventional validation remains limited and heterogeneous; key gaps include standardized assays and cutoffs, phenotype- and joint site-stratified prospective cohorts, and externally validated models demonstrating incremental prognostic utility beyond established clinical and imaging predictors.