The Association Between Serum Biomarkers of Collagen Turnover and Subsequent Anterior Cruciate Ligament Rupture

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Abstract

Background:

No study has attempted to associate the levels of preinjury serum biomarkers of collagen turnover with the subsequent risk of anterior cruciate ligament (ACL) injury.

Hypothesis:

Preinjury serum biomarkers of collagen turnover would be associated with the subsequent risk of ACL injury.

Study Design:

Case-control study; Level of evidence, 3.

Methods:

We conducted a case-control study with 45 ACL-injured cases and 45 controls matched for sex, age, height, and weight. In addition to the matching criteria, controls had no history of major joint injury. Baseline preinjury serum samples were obtained from the Department of Defense Serum Repository for all subjects. Samples were assessed for 2 serum biomarkers of collagen synthesis (CPII and CS846) and 2 markers of collagen degradation (C1,2C and C2C) through commercially available enzyme-linked immunosorbent assay (ELISA) kits. All ELISAs were performed in triplicate. Conditional logistic regression models were used to analyze the data.

Results:

Univariate results suggested that both biomarkers for collagen degradation (C1,2C and C2C) were significantly associated with the subsequent likelihood of ACL injury. Serum C2C and C1,2C concentration at baseline were associated with odds ratios (ORs) of 2.05 (95% CI, 1.30-3.23; P = .001) and 3.02 (95% CI, 1.60-5.71; P = .002), respectively. Baseline serum CPII concentrations were also associated with subsequent ACL injury. Serum CPII concentration at baseline was associated with an OR of 4.41 (95% CI, 1.87-10.38; P = .001). Baseline serum CS846 levels approached significance (OR = 0.77; 95% CI, 0.57-1.03; P = .080). Multivariable models suggested that preinjury CPII and C2C concentrations at baseline are important indicators of subsequent ACL injury risk.

Conclusion:

Preinjury differences in serum biomarker levels of collagen turnover suggest that collagen metabolism in individuals who go on to tear an ACL may be different when compared with a matched control group with no history of major joint injury. These differences may be reflective of different preinjury biochemical and/or biomechanical risk profiles or genetic factors that subsequently affect both collagen metabolism and ACL injury risk.

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