Systemic Biomarkers of Chondral Metabolism and Matrix Remodeling After Anterior Cruciate Ligament Reconstruction: A Prospective Study

Background: Anterior cruciate ligament (ACL) injuries and reconstruction are associated with alterations in chondral homeostasis and posttraumatic osteoarthritis. Biomarkers of chondral metabolism may have a role in quantitatively evaluating this phenomenon. Purposes: To describe changes in 3 systemic biomarkers of chondral metabolism and extracellular matrix remodeling during the first year after ACL reconstruction and to identify factors associated with biomarker concentrations at the baseline and 12-month postoperative timepoints. Study Design: Controlled laboratory study. Methods: From a longitudinal study, urine and serum samples were taken immediately before primary ACL reconstruction and at 6 and 12 months postoperatively. A total of 666 patients provided samples (mean ± SD age, 24.9 ± 7.2 years; 60.5% male). Immunoassays were used to measure concentrations of urinary C-terminal cross-linked telopeptide of type 2 collagen (CTX-II), a marker of type 2 collagen degradation; serum N-propeptide of collagen IIA (PIIANP), a marker of type 2 collagen synthesis; and serum matrix metalloproteinase 3 (MMP-3), a mediator of extracellular matrix remodeling. Linear mixed modeling and linear regression were used for data analysis. Results: Urinary CTX-II concentrations decreased by 25% (95% CI, 19%-31%) from baseline to 6 months and by 37% (95% CI, 22%-42%) from baseline to 12 months, respectively ( P < .001). Serum PIIANP increased by 40% (95% CI, 34%-47%) from baseline to 6 months ( P < .001) with no significant change between 6 and 12 months. Serum MMP-3 increased by 35% (95% CI, 29%-42%) and 44% (95% CI, 37%-52%) from baseline to 6 months and from baseline to 12 months respectively ( P < .001). At the baseline timepoint, age, body mass index (BMI), sex, and time from injury to surgery were factors associated with biomarker concentrations. At the 12-month timepoint, age, sex, BMI, and time from injury to surgery were associated with biomarker concentrations. Conclusion: Decreasing urinary CTX-II concentrations coupled with increasing serum PIIANP concentrations may suggest a reparative chondral response within the first 12 months after ACL reconstruction. Increasing serum MMP-3 concentrations suggested persistent and progressive extracellular matrix remodeling during this same period. Predominantly nonmodifiable demographic factors were associated with baseline and 12-month concentrations of the 3 biomarkers. Clinical Relevance: Biomarkers of chondral metabolism may have future prognostic or decision-making roles in the management of patients with ACL injury. This could include predicting posttraumatic arthritis.