title: Relationship between pre-radiographic cartilage damage following anterior cruciate ligament injury and biomarkers of cartilage turnover in clinical practice: a cross-sectional observational study.
abstract: OBJECTIVE
  To determine whether differences in synovial fluid (SF) biomarkers of collagen and proteoglycan turnover are associated with pre-radiographic damage to articular cartilage and menisci following anterior cruciate ligament (ACL) injury and are of clinical value.
  
  
  METHODS
  SF samples from ACL injured knees of 108 patients were obtained when damage to cartilages and menisci was evaluated arthroscopically. Concentrations of SF collagenase-generated cleavage neoepitope of type II collagen (C2C) were determined using ELISA and aggrecan-derived disaccharides of chondroitin-4-sulfate (Δdi-C4S), chondroitin-6-sulfate (Δdi-C6S), and keratan sulfate (KS), were measured in SF by High performance liquid chromatography (HPLC).
  
  
  RESULTS
  Radiographic examination failed to detect any intra-articular degenerative changes. The number of high-grade cartilage lesions was positively associated with age, duration after injury and the level of C2C, and negatively with the level of KS. There was no association between the number of high-grade cartilage and meniscal lesions. Multivariable logistic regression revealed significant associations of increased C2C (adjusted Odds ratio (OR) of the upper quartile to remainder of 2.49, 95% Confidence interval (CI) = 0.85-7.27) and decreased KS (adjusted OR of the lower quartile to the remainder of 3.32, 95% CI = 1.19-9.24) with the presence of three or more high-grade cartilage lesions, independent of age and duration after injury. The combined impact of increased C2C and decreased KS was 22.8 (95% CI = 1.95-265.9), far exceeding the impact of each independent biomarker.
  
  
  CONCLUSIONS
  Combinations of the C2C and KS as described here may offer greater ability to identify patients with early pre-radiographic high-grade cartilage damage compared to single clinical or biomarker parameters.
authors.affiliation: Department of Orthopedic Surgery, Nagoya University, School of Medicine, Showa, Nagoya, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Yoshida
authors.forename: T
authors.initials: T
authors.lastname: Kojima
authors.forename: K
authors.initials: K
authors.lastname: Kurokouchi
authors.forename: S
authors.initials: S
authors.lastname: Takahashi
authors.forename: H
authors.initials: H
authors.lastname: Hanamura
authors.forename: M
authors.initials: M
authors.lastname: Kojima
authors.forename: A R
authors.initials: AR
authors.lastname: Poole
authors.forename: N
authors.initials: N
authors.lastname: Ishiguro
mesh_terms: D000293:Adolescent; D000328:Adult; D053674:Aggrecans / Q000032:analysis; D016118:Anterior Cruciate Ligament / Q000378:metabolism*; D000070598:Anterior Cruciate Ligament Injuries; D002358:Cartilage, Articular / Q000000981:diagnostic imaging / Q000293:injuries / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D024043:Collagen Type II / Q000032:analysis; D003430:Cross-Sectional Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007632:Keratan Sulfate / Q000032:analysis; D016015:Logistic Models; D008297:Male; D008592:Menisci, Tibial / Q000000981:diagnostic imaging / Q000378:metabolism*; D011509:Proteoglycans / Q000032:analysis; D011859:Radiography; D013582:Synovial Fluid / Q000737:chemistry*; D000070600:Tibial Meniscus Injuries; D055815:Young Adult
chemical_list: D053674:Aggrecans; D024043:Collagen Type II; D011509:Proteoglycans; D007632:Keratan Sulfate