Cartilage Blood Biomarkers Are Linked to Two-Year Changes in Knee Cartilage Thickness and Composition After Anterior Cruciate Ligament Injury

Cartilage blood biomarkers and their load-induced changes serve as surrogate parameters to detect early changes in cartilage homeostasis in persons with or at risk of osteoarthritis. Little is known about the relationship between biomarker kinetics and longitudinal changes in articular cartilage thickness and composition (transverse relaxation time (T2), increases with osteoarthritis) after anterior cruciate ligament (ACL) injury (increased post-traumatic osteoarthritis risk). We investigated the relationship between load-induced biomarker concentration kinetics and 2-year change in knee cartilage thickness and T2 time in persons after ACL injury and healthy controls. Data of 43 participants (20–30 years) were analyzed (ACL 20–30 : unilateral ACL injury 2–10 years before baseline, n=20, age: 26.1±2.9 years, BMI: 23.6±2.6 kg/m 2 ; HEA 20–30 : healthy controls, no history of knee injury, n=23, age: 26.5±3.2 years, BMI: 22.9±2.0 kg/m 2 ). At baseline, blood samples were taken immediately before (t 0 ) and after (t 1 ) a 30-minute treadmill walking stress and analyzed for cartilage degradation (collagen II and III fragments (C2M, C3M), cartilage oligomeric matrix protein (COMP), aggrecan degradation products (ARG)), collagen formation (type II procollagen (PRO-C2)) and inflammation (interleukin-6 (IL6), only t 0 ) marker concentration. Coronal qDESS MRI (3T Siemens Prisma) was acquired baseline and 2-year follow-up. The weight-bearing femorotibial joint (FTJ) was manually segmented (Chondrometrics GmbH) to obtain mean cartilage thickness and T2 of the total, deep 50% and superficial 50% zones. Pearson correlations between biomarker concentrations (t 0 , t 1 ) and load-induced changes (t 1 -t 0 ) with 2-year changes in thickness and T2 for FTJ and subregions (medial, lateral compartment (MFTC, LFTC)) in the ACL 20–30 injured knees and HEA 20–30 left knees were evaluated. In HEA 20–30 , 5 of 192 correlations had p-values below 0.05 (≍10 expected by chance, Fig. 1). For ACL 20–30 , 31 of 192 correlations had p-values below 0.05 (Fig. 1). IL6(t 0 ) and PRO-C2(t 1 -t 0 ) correlated negatively with changes in cartilage thickness. IL6(t 0 ) and COMP(t 0 , t 1 ) correlated positively with changes in T2 of FTJ, MFTC and LFTC, and C2M(t 0 , t 1 ) correlated negatively with changes in T2 of FTJ and LFTC. PRO-C2(t 0 ) correlated negatively with changes in LFTC T2. Biomarkers such as IL6, COMP, and PRO-C2 show potential as early predictors of cartilage degeneration, particularly in ACL-injured individuals, where cartilage homeostasis is disrupted. These findings emphasize the need for further research to validate the utility of biomarkers (and their mechanoresponse) in monitoring cartilage health and guiding interventions for post-traumatic osteoarthritis. Funding: SNF: #184912 For any figures or tables, please contact the authors directly.