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Pre-injury serum biomarkers associated with risk of subsequent ACL rupture
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BALTIMORE — In an award-winning study, researchers from Texas Technical University Health Sciences Center, U.S. Military Academy at West Point and Keller Army Community Hospital discovered a link between pre-injury levels of three serum biomarkers of cartilage turnover and risk of future ACL rupture.
“Pre-injury serum biomarker concentrations for cartilage turnover appear to be associated with subsequent ACL injury,”
Svoboda presented the study, which won the O’Donoghue Sports Injury Research Award, at the American Orthopaedic Society for Sports Medicine Annual Meeting 2012.
The investigators embarked on their award-winning study after observing pre-injury baseline differences for the serum biomarkers CP II, CS846, C1/2C and C2C between ACL-injured patients and uninjured controls in a previous study.
“We hypothesized that the significant pre-injury baseline differences between the ACL-injured cases and uninjured controls for C2C, C1/2C, CPII and CS846. In addition, we also hypothesized that baseline pre-injury differences in biomarker concentrations would be associated with a likelihood of subsequent ACL rupture,” Svoboda said.
Using serum samples collected from cadets at the U.S. Military Academy at West Point taken upon entrance to the academy and 4 years later at graduation, Svoboda and colleagues studied 45 ACL-injured cases and an uninjured control group who were screened for any history of injury during their time at the academy and matched for gender, age, height and weight. The investigators used commercially available ELISA kits to analyze the samples for two biomarkers of cartilage synthesis — CPII and CS846 — and biomarkers of cartilage degradation — C2C and C1/2C.
The study group had an average age of 20 years and 87% were men. The investigators found ACL injuries occurred at an average 21 months into cadets’ time at the academy.
A univariate logistic regression analysis showed significant differences between the injured and uninjured groups for C1/2C, C2C and CPII.
“On average, 1 ng/mL increase in serum of CPII at baseline is associated with a 19 times more likely to sustain an ACL injury over 4 years at West Point,” Svoboda said. “On average, 1 ng/mL increase in C2C gives you a 9.1 times association of sustaining an ACL injury and, similarly, if C1/2C [gives] you a 4.2 times increased association of an ACL tear while you are at West Point for 4 years.”
Performing a multivariate analysis of C2C and CPII levels at baseline changed the odds ratio for subsequent ACL injury to three and 28, respectively.
Among the limitations of the study, Svoboda noted that the investigators could not control for participants’ pre-injury activity levels or the interval from serum testing to the time of ACL injury and lacked pre-injury biomechanical data on participants.
“The pre-injury differences in biomarker concentrations may reflect outward mechanical loading patterns associated with high risk biomechanical movement patterns,” Svoboda said. “Further study is needed to replicate these findings and to better understand the relationship between pre-injury biomechanics, cartilage metabolism, ACL injury risk and post-traumatic osteoarthritis.” – by Gina Brockenbrough, MA
Disclosure: Svoboda has no relevant financial disclosures. This study was aided by a grant from the Orthopaedic Research and Education Foundation. The views and opinions expressed are those of the author(s) and do not reflect the official policy of the Army, Department of Defense or the U.S. government.