Background. The majority of patients develop posttraumatic osteoarthritis within 15 years of anterior cruciate ligament (ACL) injury. Inflammatory and chondrodegenerative biomarkers have been associated with both pain and the progression of osteoarthritis; however, it remains unclear if preoperative biomarkers differ for patients with inferior postoperative outcomes. Hypothesis/Purpose. The purpose of this pilot study was to compare biomarkers collected on the day of ACL reconstruction between patients with "good" or "poor" 2-year postoperative outcomes. We hypothesized that inflammatory cytokines and chondrodegenerative biomarker concentrations would be significantly greater in patients with poorer outcomes. Study Design. Prospective cohort design. Methods. 22 patients (9 females, 13 males; age = 19.5 ± 4.1 years; BMI = 24.1 ± 3.6 kg/m2) previously enrolled in a randomized trial evaluating early anti-inflammatory treatment after ACL injury. Biomarkers of chondrodegeneration and inflammation were assessed from synovial fluid (sf) samples collected on the day of ACL reconstruction. Participants completed Knee Injury and Osteoarthritis Outcome Score (KOOS) and International Knee Documentation Committee (IKDC) questionnaires two years following surgery. Patients were then categorized based on whether their KOOS Quality of Life (QOL) score surpassed the Patient Acceptable Symptom State (PASS) threshold of 62.5 points or the IKDC PASS threshold of 75.9 points. Results. Patients that failed to reach the QOL PASS threshold after surgery (n = 6, 27%) had significantly greater sf interleukin-1 alpha (IL-1α; p = 0.004), IL-1 receptor antagonist (IL-1ra; p = 0.03), and matrix metalloproteinase-9 (MMP-9; p = 0.01) concentrations on the day of surgery. Patients that failed to reach the IKDC PASS threshold (n = 9, 41%) had significantly greater sf IL-1α (p = 0.02). Conclusion. These pilot data suggest that initial biochemical changes after injury may be an indicator of poor outcomes that are not mitigated by surgical stabilization alone. Biological adjuvant treatment in addition to ACL reconstruction may be beneficial; however, these data should be used for hypothesis generation and more definitive randomized clinical trials are necessary.
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This study received funding from The Arthritis Foundation of America and the Arthroscopy Association of North America. Research reported in this publication was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under Award no. 5K23AR060275. Data collection and study administration was supported by the University of Kentucky CTSA Award (UL1TR000117).
The datasets used to support the findings of this study are restricted by the University of Kentucky Institutional Review Board in order to protect patient privacy. Data are available from the corresponding author for researchers who meet the criteria for access to confidential data.
Lattermann, Christian; Conley, Caitlin E. -W.; Johnson, Darren L.; Reinke, Emily K.; Huston, Laura J.; Huebner, Janet L.; Chou, Ching-Heng; Kraus, Virginia B.; Spindler, Kurt P.; and Jacobs, Cale A., "Select Biomarkers on the Day of Anterior Cruciate Ligament Reconstruction Predict Poor Patient-Reported Outcomes at 2-Year Follow-Up: A Pilot Study" (2018). Orthopaedic Surgery and Sports Medicine Faculty Publications. 12.