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

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.

[1]  W. Brechue,et al.  Changes in Serum Biomarkers of Cartilage Turnover After Anterior Cruciate Ligament Injury , 2013, The American journal of sports medicine.

[2]  R. Burks,et al.  Incidence of physician-diagnosed osteoarthritis among active duty United States military service members. , 2011, Arthritis and rheumatism.

[3]  A R Poole,et al.  Application of Biomarkers in the Development of Drugs Intended for the Treatment of Osteoarthritis OARSI FDA Osteoarthritis Biomarkers Working Group , 2011 .

[4]  Lindsay J. DiStefano,et al.  Effects of an Age-Specific Anterior Cruciate Ligament Injury Prevention Program on Lower Extremity Biomechanics in Children , 2011, The American journal of sports medicine.

[5]  V. Kraus,et al.  Changes in serum and synovial fluid biomarkers after acute injury (NCT00332254) , 2010, Arthritis research & therapy.

[6]  Frances T. Sheehan,et al.  Noncontact Anterior Cruciate Ligament Injuries: Mechanisms and Risk Factors , 2010, The Journal of the American Academy of Orthopaedic Surgeons.

[7]  Rodney X. Sturdivant,et al.  Incidence of Acute Traumatic Patellar Dislocation among Active-Duty United States Military Service Members , 2010, The American journal of sports medicine.

[8]  L. Punzi,et al.  New horizons in osteoarthritis. , 2010, Swiss medical weekly.

[9]  Martin Englund,et al.  The role of biomechanics in the initiation and progression of OA of the knee. , 2010, Best practice & research. Clinical rheumatology.

[10]  T. Hewett,et al.  Reducing knee and anterior cruciate ligament injuries among female athletes: a systematic review of neuromuscular training interventions. , 2010, The journal of knee surgery.

[11]  Malcolm Collins,et al.  The COL5A1 Gene Is Associated With Increased Risk of Anterior Cruciate Ligament Ruptures in Female Participants , 2009, The American journal of sports medicine.

[12]  Rodney X. Sturdivant,et al.  Patellar Tendon Versus Hamstring Tendon Autografts for Anterior Cruciate Ligament Reconstruction , 2009, The American journal of sports medicine.

[13]  Lindsay J. DiStefano,et al.  Influence of Age, Sex, Technique, and Exercise Program on Movement Patterns after an Anterior Cruciate Ligament Injury Prevention Program in Youth Soccer Players , 2009, The American journal of sports medicine.

[14]  M. Schwellnus,et al.  Genetic risk factors for anterior cruciate ligament ruptures: COL1A1 gene variant , 2009, British Journal of Sports Medicine.

[15]  Timothy E. Hewett,et al.  Video Analysis of Anterior Cruciate Ligament Injury , 2009, The American journal of sports medicine.

[16]  Lindsay J. DiStefano,et al.  Sagittal Plane Knee Biomechanics and Vertical Ground Reaction Forces Are Modified Following ACL Injury Prevention Programs , 2009, Sports health.

[17]  Jiri Dvorak,et al.  A Randomized Controlled Trial to Prevent Noncontact Anterior Cruciate Ligament Injury in Female Collegiate Soccer Players , 2008, The American journal of sports medicine.

[18]  E. Roos,et al.  The Long-term Consequence of Anterior Cruciate Ligament and Meniscus Injuries , 2007, The American journal of sports medicine.

[19]  L. Sharma,et al.  The ratio of type II collagen breakdown to synthesis and its relationship with the progression of knee osteoarthritis. , 2007, Osteoarthritis and cartilage.

[20]  V. Kraus,et al.  Collagen Biomarkers for Arthritis Applications , 2006, Biomarker insights.

[21]  Annegret Mündermann,et al.  The role of ambulatory mechanics in the initiation and progression of knee osteoarthritis , 2006, Current opinion in rheumatology.

[22]  D J Hunter,et al.  Classification of osteoarthritis biomarkers: a proposed approach. , 2006, Osteoarthritis and cartilage.

[23]  T. Andriacchi,et al.  Secondary gait changes in patients with medial compartment knee osteoarthritis: increased load at the ankle, knee, and hip during walking. , 2005, Arthritis and rheumatism.

[24]  D. Kirkendall,et al.  Effectiveness of a Neuromuscular and Proprioceptive Training Program in Preventing Anterior Cruciate Ligament Injuries in Female Athletes , 2005, The American journal of sports medicine.

[25]  T. Hewett,et al.  Biomechanical Measures of Neuromuscular Control and Valgus Loading of the Knee Predict Anterior Cruciate Ligament Injury Risk in Female Athletes: A Prospective Study , 2005, The American journal of sports medicine.

[26]  E. Roos,et al.  Joint injury causes knee osteoarthritis in young adults , 2005, Current opinion in rheumatology.

[27]  A. Poole,et al.  The assessment of cartilage degradation in vivo: development of an immunoassay for the measurement in body fluids of type II collagen cleaved by collagenases. , 2004, Journal of immunological methods.

[28]  M. Englund,et al.  High prevalence of knee osteoarthritis, pain, and functional limitations in female soccer players twelve years after anterior cruciate ligament injury. , 2004, Arthritis and rheumatism.

[29]  M. Englund,et al.  Risk factors for symptomatic knee osteoarthritis fifteen to twenty-two years after meniscectomy. , 2004, Arthritis and rheumatism.

[30]  Gordon S. Smith,et al.  Occupational disability after hospitalization for the treatment of an injury of the anterior cruciate ligament. , 2003, The Journal of bone and joint surgery. American volume.

[31]  P. Amoroso,et al.  Risk factors for occupational knee related disability among enlisted women in the US Army , 2002, Occupational and environmental medicine.

[32]  R. LaPorte,et al.  Disabilities due to injury in the military. , 2000, American journal of preventive medicine.

[33]  P. Amoroso,et al.  Case-control study of discharge from the U.S. Army for disabling occupational knee injury: the role of gender, race/ethnicity, and age. , 2000, American journal of preventive medicine.

[34]  F. Noyes,et al.  The Effect of Neuromuscular Training on the Incidence of Knee Injury in Female Athletes , 1999, The American journal of sports medicine.

[35]  A. Poole,et al.  Changes in joint cartilage aggrecan after knee injury and in osteoarthritis. , 1999, Arthritis and rheumatism.

[36]  P. Dieppe,et al.  Evidence for altered synthesis of type II collagen in patients with osteoarthritis. , 1998, The Journal of clinical investigation.

[37]  C. Rorabeck,et al.  Enhanced cleavage of type II collagen by collagenases in osteoarthritic articular cartilage. , 1997, The Journal of clinical investigation.

[38]  F R Noyes,et al.  Plyometric Training in Female Athletes , 1996, The American journal of sports medicine.

[39]  K. Markolf,et al.  Combined knee loading states that generate high anterior cruciate ligament forces , 1995, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[40]  C. Harner,et al.  Detailed Analysis of Patients with Bilateral Anterior Cruciate Ligament Injuries , 1994, The American journal of sports medicine.

[41]  A. Poole,et al.  Studies of the articular cartilage proteoglycan aggrecan in health and osteoarthritis. Evidence for molecular heterogeneity and extensive molecular changes in disease. , 1992, The Journal of clinical investigation.

[42]  D. Felson.  The epidemiology of knee osteoarthritis: results from the Framingham Osteoarthritis Study. , 1990, Seminars in arthritis and rheumatism.

[43]  P. Roughley,et al.  Age-related changes in protein-related epitopes of human articular-cartilage proteoglycans. , 1986, The Biochemical journal.

[44]  Abbey C. Thomas,et al.  Osteoarthritis-related biomarkers following anterior cruciate ligament injury and reconstruction: a systematic review. , 2015, Osteoarthritis and cartilage.

[45]  W. Dunn,et al.  Incidence of anterior cruciate ligament injury among active duty U.S. military servicemen and servicewomen. , 2007, Military medicine.

[46]  Thomas P Andriacchi,et al.  The mechanical consequences of dynamic frontal plane limb alignment for non-contact ACL injury. , 2006, Journal of biomechanics.

[47]  T. Andriacchi,et al.  Serum concentration of cartilage oligomeric matrix protein (COMP) is sensitive to physiological cyclic loading in healthy adults. , 2005, Osteoarthritis and cartilage.