Combination of Synovial Fluid Biomarkers Enables Accurate Detection of Early Knee Osteoarthritis

Abstract Objective Early diagnosis of osteoarthritis (OA) remains challenging due to the limited sensitivity of clinical and radiographic methods. This study aimed to identify a combination of soluble biomarkers in synovial fluid (SF) and serum that could reliably discriminate early-stage OA and serve as a complementary diagnostic tool. Design A prospective observational study was conducted including three patient groups stratified according to the Kellgren–Lawrence grading system. Synovial fluid and serum samples were collected during routine clinical procedures. The following biomarkers were analysed: periostin, aggrecan (ACAN), leptin, high-sensitivity C-reactive protein (hsCRP), hypoxia-inducible factor 1 alpha (HIF-1α), CXCL12 (SDF-1), Cartilage Acidic Protein 1 (CRTAC1), and C-terminal telopeptide of type II collagen (CTX-II). Statistical analysis included Spearman correlation and multinomial regression with elastic net regularisation. Results Significant differences between groups were observed for SF ACAN, serum ACAN, SF leptin, serum leptin, SF white blood cells (WBC), SF mononuclear cells, serum hsCRP, and SF CRTAC1 ( p < 0.05). Synovial fluid biomarkers demonstrated greater discriminatory potential than serum markers. Multivariate analysis identified 15 predictors of early OA. A reduced model including five key variables (age, SF WBC, SF ACAN, SF CRTAC1, and SF leptin) achieved an accuracy of 0.807. Conclusions Individual biomarkers showed limited diagnostic value, whereas a combination of selected synovial fluid biomarkers together with age enabled reliable discrimination of early OA. These findings support the use of a combination of markers as a preliminary strategy for improving early OA diagnosis.