Abstract
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.
Highlights
Whether isolated or in concert with concomitant meniscal or articular cartilage injury, anterior cruciate ligament (ACL) rupture initiates a cascade of cytokine and catabolic enzyme activity [1,2,3,4]
We hypothesized that synovial fluid and urine concentrations of inflammatory cytokines and chondrodegenerative biomarkers would be significantly greater in patients with poorer outcomes
Patients that failed to reach the Quality of Life (QOL) Patient Acceptable Symptom State (PASS) threshold had significantly greater sf IL-1훼 (p=0.004), sf IL-1 receptor antagonist (IL-1ra) (p=0.02), and sf matrix metalloproteinase-9 (MMP-9) (p=0.01)
Summary
Whether isolated or in concert with concomitant meniscal or articular cartilage injury, anterior cruciate ligament (ACL) rupture initiates a cascade of cytokine and catabolic enzyme activity [1,2,3,4]. Regardless of surgical or conservative management, the majority of patients develop posttraumatic osteoarthritis (PTOA) within 15 years of ACL injury [5,6,7]. The majority of patients develop posttraumatic osteoarthritis within 15 years of anterior cruciate ligament (ACL) injury. 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. 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. Participants completed Knee Injury and Osteoarthritis Outcome Score (KOOS) and International Knee Documentation Committee (IKDC) questionnaires two years following surgery. Biological adjuvant treatment in addition to ACL reconstruction may be beneficial; these data should be used for hypothesis generation and more definitive randomized clinical trials are necessary
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