Prediction of progression of damage to articular cartilage 2 years after anterior cruciate ligament reconstruction: use of aggrecan and type II collagen biomarkers in a retrospective observational study

BACKGROUND We aimed to determine whether synovial fluid (SF) biomarkers can predict the progression of articular cartilage damage as determined by arthroscopic evaluation during and after anterior cruciate ligament (ACL) reconstruction. METHODS Arthroscopic assessment of articular cartilage damage was performed twice in 62 patients, first during ACL reconstruction and then approximately 2 years later during implant removal for ligament fixation. SF levels of the collagenase-generated cleavage neoepitope of type II collagen (C2C) and proteoglycan glycosaminoglycans keratan sulfate (KS), chondroitin-4-sulfate (Δdi-C4S), and chondroitin-6-sulfate (Δdi-C6S) were measured at ACL reconstruction. Associations between baseline biomarker levels and subsequent progression of cartilage damage were determined using receiver operating characteristic analysis and multivariable logistic regression analysis. RESULTS No radiographic changes were observed in any of the patients. Progression of high-grade cartilage damage, observed arthroscopically, was negatively correlated with levels of Δdi-C6S and KS, as well as the ratio of Δdi-C6S to Δdi-C4S (C6S/C4S). Logistic regression analysis revealed significant associations of Δdi-C6S (cut-off: 55.7 nmol/ml, odds ratio (OR) 0.231, 95% confidence interval (CI) 0.061-0.879), KS (cut-off: 10.6 μg/ml, OR 0.114, 95% CI 0.024-0.529), and C6S/C4S ratio (cut-off: 4.6, OR 0.060, 95% CI 0.005-0.737) with the progression of high-grade cartilage damage after adjusting for age, the duration from injury to first surgery, sex, and the number of high-grade lesions (grades III and IV) at baseline. CONCLUSIONS The progression of high-grade cartilage damage was significantly associated with baseline levels of proteoglycan glycosaminoglycan biomarkers; namely, Δdi-C6S, KS, and C6S/C4S ratio.