Higher Day of Surgery Serum Matrix Metalloproteinase-3 Concentration Is Associated With Failing to Achieve the KOOS-4 and IKDC Patient Acceptable Symptom State at 6 Years After ACL Reconstruction

Abstract

Background:

The risk of posttraumatic arthritis is elevated after anterior cruciate ligament (ACL) injury, and this can influence follow-up patient-reported outcome measures (PROMs). Biomarkers of chondral and matrix metabolism may represent a means of quantitatively evaluating the posttraumatic arthritis pathological process.

Purpose:

To assess for a longitudinal association between 3 systemic (blood and/or urine) biomarkers of chondral and matrix metabolism as measured on the day of ACL reconstruction with poor PROMs 6 years later.

Study Design:

Descriptive laboratory study.

Methods:

From a prospective longitudinal study, urine and serum samples were taken immediately before primary ACL reconstruction in 642 patients (mean age, 25.02 years; 60.3% men). Three biomarkers of chondral and matrix metabolism were measured using immunoassays: urinary C-terminal cross-linked telopeptide of type 2 collagen (u-CTX-II), serum N-propeptide of collagen 2A (s-PIIANP), and serum matrix metalloproteinase-3 (MMP-3). Six years postoperatively, patients completed the International Knee Documentation Committee (IKDC) Subjective Knee Form and Knee injury and Osteoarthritis Outcome Score-4 (KOOS-4) PROMs. PROMs were dichotomized based on Patient Acceptable Symptom State (PASS) thresholds. After exclusion of patients with outlier biomarker values and missing data, univariate (n = 411 for KOOS-4 and n = 419 for IKDC) and multivariate (n = 366 for KOOS-4 and n = 373 for IKDC) logistic regression models were developed with baseline biomarker concentrations and surgical and demographic parameters as predictive variables.

Results:

In the multivariate model, higher baseline s-MMP-3 (OR, 0.98; P = .009) and increased articular cartilage pathology at surgery (OR, 0.87; P = .040) were associated with not achieving a KOOS-4 PASS. Higher baseline s-MMP-3 (OR, 0.98; P = .031), increased articular cartilage pathology at surgery (OR, 0.88; P = .045), and higher preoperative body mass index (BMI) (OR, 0.91; P = .027) were associated with not achieving a IKDC PASS. A medial meniscus tear that was resected was associated with achieving the IKDC PASS relative to no medial meniscus tear (OR, 3.34; P = .017). In the univariate modeling, older age and higher BMI were additionally associated with not achieving a KOOS-4 PASS (all P≤ .017). In the IKDC univariate modeling, lower baseline s-PIIANP, higher u-CTX-II, increasing age, and a lower preoperative Marx score were additionally associated with failing to achieve the PASS threshold (all P≤ .043).

Conclusion:

Increased s-MMP-3 concentration on the day of surgery was associated with failing to achieve the PASS threshold for both the KOOS-4 and IKDC PROMs at the 6-year time point after ACL reconstruction.

Clinical Relevance:

This day of surgery blood test may be helpful in identifying patients at risk of a poor outcome 6 years after ACL reconstruction. In turn, this could help define a target group for evaluating interventions aimed at preventing posttraumatic arthritis.