Summary

Day of surgery serum MMP-3 is independently associated with 6 year PROMS after ACL reconstruction

Abstract

Introduction/objectives:

The risk of post traumatic arthritis is elevated after anterior cruciate ligament (ACL) injury, and this can influence patient reported outcome measures (PROMs). Biomarkers of chondral and matrix metabolism may represent a means of quantitatively evaluating the post traumatic arthritis pathological process. The aim of this study was to assess for a longitudinal association between three systemic biomarkers of chondral and matrix metabolism as measured on the day of surgery to poor PROM scores at 6-years after primary ACL reconstruction.

Methods

From a prospective longitudinal study, urine and serum samples were taken immediately prior to primary ACL reconstruction in 660 patients (mean age 25.02 years, 60.5% male). Concentrations of three biomarkers of chondral and matrix metabolism were measured using immunoassays. The biomarkers were urinary C-terminal cross-linked telopeptide of type II collagen (CTX-II), serum N-propeptide of collagen IIA (PIIANP) and serum Matrix Metalloproteinase 3 (MMP-3). At six years post operatively, patients completed the International Knee Documentation Committee Subjective Knee Form (IKDC) and Knee Osteoarthritis and Outcome Score-4 (KOOS-4) PROMs. PROM scores were dichotomised based on patient acceptable symptoms state (PASS) thresholds. After exclusion of patients with outlier biomarker values and missing data, univariate (n=411) and multivariate (n=358) logistic regression models were developed with IKDC and KOOS-4 PASS as the dependent variable and baseline biomarker concentrations, clinical and demographic parameters as predictive variables.

Results

In the multivariate model, higher baseline serum MMP-3 (OR 0.98, p=0.014) was associated with not achieving a KOOS-4 PASS at the 6-year post operative timepoint. Higher baseline serum MMP-3 (OR 0.98, p=0.034) and higher preoperative BMI (OR 0.91, p=0.024) were associated with not achieving a IKDC PASS at the same timepoint. In the univariate modelling, older age, higher articular cartilage scores and higher BMI were additionally associated with not achieving a KOOS-4 PASS (p<0.01). For the IKDC univariate modelling, lower baseline serum PIIANP, higher urinary CTX-II, lower age, a higher articular cartilage score and a lower preoperative Marx score were additionally associated with failing to achieve the PASS threshold.

Conclusion

Increased serum MMP-3 concentration on the day of surgery was independently associated with failing to achieve the PASS threshold for both the KOOS-4 and IKDC PROMs at the 6-year timepoint following ACL reconstruction.