Poster 242: Exploring the Correlation Between Synovial Fluid Cytokine Profiles and Meniscal Treatment Outcomes

Abstract

Objectives: Meniscal tears are a common injury and have been shown to contribute to the development of posttraumatic osteoarthritis (PTOA) in affected individuals. Research indicates that meniscal repair yields more favorable outcomes compared to partial and subtotal meniscectomies, with a protective effect against the incidence of PTOA. The aim of this study was to investigate whether a distinct synovial fluid profile was associated with meniscal injuries amenable to repair, thereby shedding light on potential biomarkers or factors that may predict treatment selection and improve preoperative patient counseling. Methods: Patients were prospectively recruited between January 2011 and the present and were enrolled on the day of surgery. The operative knee was aspirated aseptically, following skin preparation and patient draping. The synovial fluid was analyzed to determine concentrations of biomarkers. Patients with meniscal injuries and complete synovial fluid results for all 10 cytokines were included: Regulation on Activation Normal T Cell Expressed and Secreted (RANTES), Interleukin 6 (IL-6), Monocyte Chemoattractant Protein 1 (MCP-1), Macrophage Inflammatory Protein-1 beta (MIP-1b), Vascular Endothelial Growth Factor (VEGF), Tissue Inhibitor Matrix Metalloproteinase 1 and 2 (TIMP-1, TIMP-2), Interleukin 1 Receptor Antagonist (IL1-RA), and Matrix Metalloproteinase 3 (MMP-3). Elite athletes were excluded from analysis. Hierarchical clustering was performed on the biomarker concentrations to identify two distinct clusters. The percentage of patients with meniscal tears amenable to repair and synovial fluid levels were compared between the identified clusters using the chi-square test and t test. Results: A total of 183 patients were included, of which 46 underwent a meniscal repair. The average body mass index (BMI) was 27.95 ± 5.63, and the mean age at the time of surgery was 38.48 ± 10.19. The cohort consisted of 58.5% male patients. There was a significantly higher proportion of patients who experienced a bucket handle tear in those who underwent a repair procedure versus a meniscectomy (21.7% vs. 5.1%, p = 0.002). There was no other difference in meniscal tear patterns between the groups (posterior horn, p = 0.062; anterior horn, p = 0.34; radial, p = 0.17; body, p = 1). Through hierarchical clustering, the analysis identified two distinct clusters: cluster 1, comprising 115 patients, and cluster 2, consisting of 68 patients. There were no significant differences in age (38.51 vs. 38.43, p = 0.96), sex (55.7% vs. 63.2% male, p = 0.11) or BMI (27.85 vs. 28.13, p = 0.75) between the 2 clusters. Cluster 1 exhibited a higher rate of meniscal tears amenable to repair as compared to cluster 2 (24.3% vs. 8.8%, p = 0.016). Furthermore, cluster 1 had a higher percentage of reported cartilage injuries (11.3% vs. 1.5%, p = 0.033). Additionally, cluster 1 showed higher log-transformed concentrations of MIP-1b (3.56 vs. 3.18, p = 0.002), TIMP-1 (13.06 vs. 10.08, p < 0.001), and TIMP-2 (10.56 vs. 7.20, p < 0.001), while demonstrating lower concentrations of RANTES (4.08 vs. 4.86, p = 0.008) compared to cluster 2. Stepwise logistic regression was performed to identify the cytokines that are associated with the likelihood of a repairable meniscal tear, controlling for age, sex, BMI, cartilage lesion grade, and meniscal pathology. The resulting model included sex, posterior horn tear, handle tear, radial tear, body tear and bucket handle tear, which is a known confounder for meniscal repair, and revealed statistically significant relationships between certain biomarkers and the odds of encountering a repairable tear. Specifically, MCP-1, TIMP-2, and MMP-3 were significantly associated with the odds of a repairable meniscus. The amenability of meniscal repair decreased by 76% (95% CI: 0.64 - .69, p = 0.017), for each unit increase of pre-operative levels of MCP-1, increased by 74% for TIMP-2 (95% CI: 1.06 – 3.00, p = 0.032), and increased by 88% for MMP-3 (95% CI: 1.18 – 3.34, p = 0.014). Conclusions: The study findings provide insights into the relationship between synovial fluid biomarkers and meniscal tear patterns. The analysis revealed a distinct group of patients (cluster 1) characterized by higher concentrations of anti-inflammatory cytokines (TIMP-1 and TIMP-2) and lower levels of the pro-inflammatory cytokine RANTES, suggesting a potential correlation between a more favorable cytokine profile and the feasibility of meniscal repair. The elevated concentrations of TIMP-1 and TIMP-2 in cluster 1 suggest an enhanced ability to regulate matrix metalloproteinases (MMPs), resulting in reduced degradation of the extracellular matrix and a potentially more favorable environment for meniscal repair. These results provide evidence suggesting that the synovial fluid cytokine profile may represent the likelihood that a meniscal tear is repairable. This knowledge has the potential to inform treatment decisions and enhance preoperative patient counseling by identifying individuals who are more likely to have meniscal pathology amenable to repair as opposed to necessitating partial or subtotal meniscectomy.