Synovial Fluid Biomarkers at the Time of Arthroscopy Predict Five-Year Outcomes

Abstract

Injury-induced molecular changes in the intra-articular microenvironment of the knee are thought to play a role in the development of post-traumatic osteoarthritis. The purpose of this study was to evaluate the association between post-traumatic synovial fluid biomarker concentrations and intermediate-term functional outcomes. Patients undergoing primary knee arthroscopy for ACL injury, meniscus injury, and/or focal chondral lesions were prospectively enrolled. Synovial fluid aspirate, collected immediately prior to surgical incision, was processed and analyzed using a multiplex magnetic bead immunoassay to determine the concentration of 10 pre-determined cytokines and chemokines. Patients with a minimum of five years of postoperative follow-up were surveyed with Visual Analog Pain Scale (VAS), Lysholm Knee Scoring Scale, and Knee Injury and Osteoarthritis Outcome Score Physical Function Shortform (KOOS-PS). Stepwise regression was used to fit a linear regression model and model accuracy was evaluated using k-fold cross validation. 39 patients (mean age: 41.56 +/- 15.98 years, mean postoperative follow-up: 6.79 +/- 0.72 years) were included in the study. Mean Lysholm, KOOS-PS, and VAS scores were 83.67 +/- 17.64, 88.37 +/- 12.79, and 11.03 +/- 19.84, respectively. 11 patients had undergone further ipsilateral knee surgery during the follow-up period. Of the remaining 28 patients, a model consisting of VEGF, TIMP-2, and MMP-3 was found to most accurately predict intermediate-term functional outcomes. Regardless of the type or extent of injury, these three biomarkers were able to explain 60.35%, 34.75%, and 39.38% of the variability in Lysholm, KOOS-PS, and VAS scores, respectively. By measuring the concentrations of MMP-3, TIMP-2, and VEGF at the time of surgery, functional outcomes and level of pain can be predicted at 5 years postoperatively with moderate accuracy. This suggests that these biomarkers may play an important role in the development of post-traumatic osteoarthritis and may serve as potential targets for therapeutic intervention.