Assessment of Serum Syndecan-4 in Patients with Knee Osteoarthritis and Its Correlation with Disease Severity

Background Osteoarthritis (OA) is the most common degenerative joint disease and a leading cause of pain and disability worldwide. Currently, the diagnosis and severity of OA are based on clinical and radiological criteria which are usually fail to detect the disease early. Syndecan-4 Syndecan-4 (SDC-4) is a transmembrane heparan sulfate proteoglycan involved in extracellular matrix interactions, inflammatory signalling and regulation of cartilage-degrading enzymes such as ADAMTS-5 and MMPs. Shed (soluble) SDC-4 has been detected in osteoarthritic synovial fluid and linked to radiographic severity, however evidence on circulating (serum) SDC-4 is more limited, although its possible role as an early diagnostic biomarker due to its role in OA pathogenesis. The purpose of this study was to evaluate serum SDC-4 concentrations in individuals with knee osteoarthritis (KOA) and to investigate its association with both clinical symptoms and radiological indicators of disease severity. Methods This prospective case-control study was conducted on 47 KOA patients fulfilling EULAR criteria and 43 matched healthy controls. Clinical assessment included WOMAC scores, pain VAS, and physical examination. SDC-4 serum levels were measured using ELISA. Radiographic severity was evaluated by Kellgren–Lawrence (KL) grading, osteophytes, joint space narrowing (JSN), bone contour deformity, and subchondral sclerosis. Statistical analyses included t-tests, ANOVA, and correlation tests. Results Serum SDC-4 concentrations were markedly increased in KOA patients relative to control group (15.9 ± 7.5 vs. 5.3 ± 2.6 ng/ml, p < 0.001). Higher SDC-4 levels correlated positively with WOMAC pain, stiffness, physical function, and total scores (p ≤ 0.05). Radiographic features including osteophytes, JSN, bone contour deformity, and subchondral sclerosis were all correlated with higher SDC-4 levels (p < 0.001). Moreover, SDC-4 levels increased with KL grade, showing significant differences between grades 2, 3, and 4 (p < 0.001). Conclusion Elevated serum SDC-4 is strongly associated with clinical symptoms and radiographic severity of KOA, suggesting its utility as a promising biomarker for disease assessment and progression.