Systemic concentrations of cartilage oligomeric matrix protein, neo-epitope of MMP-derived type III collagen fragment, and propeptide of type IV collagen are greater in those at risk of post-traumatic osteoarthritis in comparison to matched controls

Abstract Background Intra-articular knee injuries substantially increase the risk of post-traumatic osteoarthritis (PTOA). Identifying systemic biomarkers that reflect early joint tissue remodelling may improve detection of PTOA related biological activity following injury. However, no circulating biomarkers have been established for this population. This study examined whether systemic extracellular matrix protein fragments differ in young adults 1–7 years after surgically managed intra-articular knee injury compared with matched uninjured controls. Secondary aims were to evaluate the discriminative performance of a biomarker panel and explore associations with PTOA illness. Methods Thirty-eight individuals with prior surgically managed intra-articular knee injury and 38 matched uninjured controls participated. Groups were matched for sex, age, body composition, and aerobic capacity. After 30 min of non-weight bearing rest, serum and plasma samples were collected and biomarkers reflecting extracellular matrix turnover, inflammation and adiposity were quantified using immunoassay. Multivariate and univariate analyses were performed, and discriminative performance was evaluated using receiver operating characteristic analysis with leave-one-pair-out cross-validation. Results Multivariate analysis demonstrated significant separation between groups (R² = 0.09, p = 0.0004), driven by biomarkers reflecting cartilage oligomeric matrix protein and type III and type IV collagen turnover. Univariate analyses showed moderate-to-large paired effects for these biomarkers. A combined three-biomarker model demonstrated acceptable discrimination (area under the curve = 0.77, 95% confidence interval 0.66–0.87), which remained robust under cross-validation (area under the curve = 0.73, 95% confidence interval 0.61–0.84). Conclusions Systemic biomarkers of extracellular matrix remodelling differ in young adults following surgically managed intra-articular knee injury. A multivariate biomarker panel may capture early PTOA-related biological activity and support future risk stratification.