LAUSR

Objectives: Individuals sustaining anterior cruciate ligament (ACL) injuries are at increased risk for post-traumatic osteoarthritis (PTOA). Methods to discern early physiologic changes associated with PTOA are lacking. Surrogate measures of OA that may include soluble biomarkers of cartilage metabolism and pain measures have been correlated with early OA development as well. It was the objective of this study to determine whether serum biomarkers related to Type II collagen metabolism are associated with pain measures at an early time point after ACL injury. Methods: Cadets at a U.S. Service Academy who sustained primary ACL injuries were enrolled in a prospective cohort study to evaluate the relationship of WOMAC Pain Scores with serum and urine levels of C2C. C2C is an epitope of Type II collagen produced by the breakdown of the Type II collagen fibrils in articular cartilage. Questionnaires assessing the WOMAC score were completed at the time of injury with serum and urine samples obtained at the time of ACL reconstruction. Commercially available C2C ELISA tests (Ibex Pharmaceuticals, Quebec, CA) were performed on the samples from subjects obtained at the time of surgery using kits from the same production batch and reported as ng/ml±SD. Pearson correlations were calculated with significance set at p≤0.05. Results: A total of 12 subjects met the inclusion criteria and had a questionnaire completed at time of injury and fluid samples obtained at the time of ACL reconstruction surgery. The average time from injury to the time of surgery was 30.7±15.5 days. The mean serum C2C concentration at the time of surgery was 1.12 ±0.20 ng/ml and the mean urine C2C concentration was 2.12±0.51 ng/ml. The mean WOMAC Pain score was 72±21 points. The WOMAC Pain scores at the time of initial injury were inversely correlated (r=-0.609 , p=0.036) with serum C2C concentrations at the time of surgery approximately 4 weeks later. WOMAC Pain scores at the time of ACL injury accounted for 37% of the variability in serum C2C concentrations at the time of ACL reconstruction (Figure 1A). Similar results were observed for the correlation between WOMAC Pain scores at the time of injury and urine C2C concentrations at the time of surgery. The WOMAC Pain scores at the time of initial injury were also inversely correlated (r=-0.759, p=0.004) with urine C2C concentrations at the time of surgery. WOMAC Pain scores at the time of ACL injury accounted for 58% of the variability in urine C2C concentrations at the time of surgery. Conclusion: We observed a strong inverse correlation between WOMAC Pain scores at the time of ACL injury and serum and urine C2C concentrations measured at the time of ACL reconstruction approximately 4 weeks later. These preliminary findings suggest that subjects who initially report greater deficits on the WOMAC Pain scale following ACL injury also appear to have greater concentrations of Type II collagen degradation markers in both serum and urine at the time of ACL reconstruction. These findings may have implications for subsequent OA risk following acute traumatic knee joint injury.