DOI: 10.1177/03635465261493224 ISSN: 0363-5465

Longitudinal Serum Biomarker Profiles of Inflammation and Cartilage Matrix Metabolism During the First Year After Anterior Cruciate Ligament Reconstruction

Sergio A. Lemus, Jeffrey T. Spang, Lara Longobardi, Hope C. Davis-Wilson, R. Alexander Creighton, Richard F. Loeser, Ganesh M. Kamath, Todd A. Schwartz, Yvonne Golightly, Amanda E. Nelson, Brian Pietrosimone
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Background:

Anterior cruciate ligament (ACL) injury initiates biological processes linked to joint tissue degeneration. The longitudinal time course of serum biomarkers reflecting inflammation and cartilage metabolism after ACL reconstruction (ACLR), particularly in comparison with uninjured controls, has not been characterized across the first postoperative year.

Hypothesis:

Inflammatory (monocyte chemoattractant protein-1 [MCP-1]) and degradative (matrix metalloproteinase-3 [MMP-3]) biomarker concentrations would be elevated pre-ACLR and decrease over time, whereas cartilage turnover biomarker concentrations (cartilage oligomeric matrix protein [COMP] and type II collagen degradation-to-synthesis ratio [C2C:CPII]) would increase postoperatively. Also, pre-ACLR biomarker concentrations would be associated with concentrations at 6 and 12 months post-ACLR.

Study Design:

Cohort study; Level of evidence, 2.

Methods:

A total of 33 individuals with ACL injuries (52% female; mean age, 20.8 ± 2.4 years) were evaluated pre-ACLR and at 6 and 12 months post-ACLR. A total of 33 matched uninjured controls were included. Serum concentrations of MCP-1, MMP-3, COMP, and C2C:CPII were assessed using enzyme-linked immunosorbent assays. Linear mixed-effects models with model-based contrasts were used to evaluate differences across groups and time points. ACLR-only linear mixed-effects regression models were used to assess associations between pre-ACLR and follow-up biomarker concentrations. Exploratory post hoc models evaluated differences by concomitant injury status.

Results:

MCP-1 was elevated in individuals with ACL injuries compared with controls at all ACLR time points (all P adj < .001), with no change across ACLR time points. MMP-3 increased from pre-ACLR to 6 months post-ACLR ( P adj < .001) but did not differ from controls at any time point. COMP was consistently greater in individuals with ACL injuries than in controls at all time points (all P adj ≤ .021), with no changes across ACLR time points. C2C:CPII was greater at 12 months post-ACLR than at pre-ACLR and 6 months post-ACLR (both P adj < .001) and than in uninjured controls ( P adj = .001). Pre-ACLR MCP-1, MMP-3, and COMP concentrations were associated with concentrations at both 6 and 12 months post-ACLR (all P ≤ .006), whereas C2C:CPII was associated only with 12-month concentrations ( P = .018).

Conclusion:

Inflammatory and cartilage-related biomarkers remain altered throughout the first year after ACLR, suggesting that the biological response is not fully resolved by reconstruction and standard rehabilitation but extends beyond the early postoperative period.

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