Background: Meniscal injuries trigger a local inflammatory response mediated by intra-articular mediators. Proinflammatory cytokines and chemokines can lead to cartilage degradation and subchondral bone changes, contributing to posttraumatic osteoarthritis. The role that age plays in this inflammatory response is unclear. Purpose: To investigate age-dependent variation in cytokine types and concentrations in knee synovial fluid after meniscal injury. Study Design: Cohort study; Level of evidence, 3. Methods: Patients undergoing arthroscopic knee surgery for isolated meniscal injury were prospectively enrolled between July 2011 and April 2024. Synovial fluid was aspirated from the operative knee, and concentrations of 10 biomarkers were measured. Patients at least 9 years after surgery were invited to complete patient-reported outcome (PRO) surveys. Multivariable linear regression assessed pairwise relationships between age at surgery, log-normalized biomarker concentrations, and PROs, while adjusting for relevant covariates. Conditional process analysis was used to explore age-biomarker relationships, with symptom duration as a moderator and baseline Outerbridge grade as a mediator. Results: The study included 160 patients for biomarker analysis with a mean ± SD age of 50.2 ± 12.5 years. Forty-seven patients who reached a minimum 9 years of follow-up completed PRO surveys. Mean follow-up was 10.2 ± 1.3 years. Regression analysis revealed positive associations between age and log-normalized concentration of preoperative IL-6. Moderator analysis found age to be positively associated with IL-6, VEG-F, and IL-1Ra in chronic meniscal injuries. Mediator analysis found an indirect positive relationship between age and MIP-B, VEGF, and MMP-3 and an indirect negative relationship between age and TIMP-1 and TIMP-2. Preoperative TIMP-1 was positively associated with 10-year Knee injury and Osteoarthritis Outcome Score–Physical Function Short Form score and elevated in treatment responders. Conclusion: Age at surgery was associated with higher concentrations of proinflammatory biomarkers and lower concentrations of anti-inflammatory biomarkers in the synovial fluid before meniscal surgery. Anti-inflammatory markers were associated with improved long-term PROs. These findings suggest an age-related intensification of the proinflammatory response and inhibition of the anti-inflammatory response that may contribute to long-term functional decline in older patients after meniscal surgery. There is potential for age-specific immunomodulatory therapeutic strategies to manage inflammation and mitigate the progression toward posttraumatic osteoarthritis in older patients.

Background: The knee’s inflammatory response to ligamentous, meniscal, and cartilage injuries is complex and incompletely understood, particularly in the setting of concomitant injuries. Recent research has highlighted the potential utility of synovial fluid biomarker analysis in identifying factors involved in the progression of posttraumatic osteoarthritis. Purpose: To investigate if unique patterns of knee injury are associated with distinct synovial fluid biomarker profiles at the time of surgical intervention. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Patients undergoing arthroscopic knee surgery were prospectively enrolled and asked to complete the Lysholm Knee Scoring Scale and visual analog scale for pain preoperatively. Synovial fluid was aspirated from the operative knee before surgical incision, and the concentrations of 10 biomarkers of interest were quantified. Patients with intraoperative evidence of articular cartilage, meniscal, and/or anterior cruciate ligament (ACL) injury were identified and included for subsequent analysis. Biomarker concentrations were log-normalized and standardized. Principal component analysis (PCA) was performed using biomarker variables to reduce dimensionality and extract key patterns. Multivariable linear regression for each retained principal component (PC) was performed with the predictors of age, sex, body mass index, symptom duration, ACL injury, meniscal injury, and Outerbridge grade. A separate regression analysis was performed to assess relationships between PCs and patient-reported outcomes controlling for the same variables. Results: A total of 387 patients were included in the analysis, of whom 176 (45.5%) had ACL rupture, 327 (84.5%) had meniscal injury, and 225 (58.1%) had cartilage injury. PCA yielded 3 PCs (PC1, PC2, and PC3) that explained 66.9% of variance in biomarker data. PC1 was found with significant loadings of VEGF, IL-6, MMP-3, MIP-1β, and MCP-1; PC2 with TIMP-1 and TIMP-2; and PC3 with RANTES, bFGF, and IL-1RA. Multivariable linear regression found ACL injury ( P = .014; β = .164) and meniscal injury ( P = .029; β = .118) to be positively associated with PC1, Outerbridge grade to be negatively associated with PC2 ( P = .041; β = –.132), and ACL injury to be positively associated with PC3 ( P = .035; β = .141). PC1 was associated with a worse preoperative Lysholm score ( P = .001; β = –.199). Conclusion: Cartilage lesions exhibited a synovial fluid inflammatory profile distinct from ACL and meniscal injury at the time of knee arthroscopy. While ACL and meniscal injuries displayed a pro-inflammatory phenotype, more severe cartilage lesions were associated with a reduced presence of anti-inflammatory markers. The pro-inflammatory phenotype also independently correlated with worse baseline knee function. These findings contribute to the understanding of the pathophysiology of ligamentous, meniscal, and cartilage injuries and may aid in the identification of pathology-specific treatments to help alter the natural history of disease.

Background: Synovial fluid (SF) biomarkers demonstrate time-dependent variation after acute knee injury, and it is postulated that persistently elevated inflammatory markers may mediate worse long-term outcomes. Purpose: This study investigated the relationship between biomarkers in SF at the time of meniscectomy and long-term patient-reported outcomes in patients with acute versus chronic meniscal injuries. Study Design: Cohort study; Level of evidence, 3. Methods: This retrospective analysis included patients who underwent knee SF aspiration on the day of arthroscopic meniscectomy between October 2011 and October 2020 with minimum 4-year follow-up. SF aspirated from the operative knee was analyzed for 10 pro- and anti-inflammatory biomarkers. Patients completed the visual analog scale for pain, Lysholm Knee Questionnaire, Tegner Activity Scale, and Knee injury and Osteoarthritis Outcome Score–Physical Function Short-form (KOOS-PS) before surgery and at follow-up. Patients were categorized as having acute (1 year) symptoms. K-means clustering analysis was performed using biomarker levels to group patients into distinct cohorts. Results: Of 85 patients meeting inclusion criteria, 55 had chronic and 30 had acute meniscal pathology, with 62 (72.9%) completing patient-reported outcome surveys at a mean follow-up of 8.66 years (SD, 2.27). K-means clustering identified 2 distinct biomarker profiles: a high-inflammation cluster and a low-inflammation cluster. The high-inflammation cluster had higher levels of 7 proinflammatory biomarkers as compared with the low-inflammation cluster ( P = .015). The low-inflammation cluster predominantly comprised chronic meniscal injuries (89.2%), whereas the high-inflammation cluster was divided between acute and chronic cases. There were no differences in postoperative outcomes between clusters in the overall cohort. However, within the chronic cohort, the high-inflammation cluster exhibited worse postoperative scores on the visual analog scale for pain ( P = .035), Lysholm questionnaire ( P = .007), KOOS-PS ( P = .038), and Tegner scale ( P = .049) and had a higher rate of postoperative injections ( P = .020) than the low-inflammation cohort. Conclusion: In patients with chronic meniscal injury, those with a more proinflammatory SF biomarker profile at the time of meniscectomy had worse outcomes than those who had a low inflammatory profile. In acute meniscal injuries, most patients demonstrate a high inflammatory profile, which was not associated with a difference in long-term outcomes.