title: Biomarker Changes in Anterior Cruciate Ligament-Deficient Knees Compared With Healthy Controls.
abstract: OBJECTIVE
  To establish how synovial fluid biomarker concentrations change in patients after anterior cruciate ligament (ACL) tears, with and without associated cartilage injury, with comparisons made to healthy controls.
  
  
  METHODS
  Patients were prospectively enrolled between January 2013 and December 2014. Inclusion criteria included any patient undergoing knee arthroscopy. Patients with a confirmed ACL tear were allocated to either the ACL tear with cartilage injury group or the ACL tear without cartilage injury group based on intraoperative assessment. Patients who underwent an arthroscopic procedure with no injury history or symptoms in their contralateral knee were asked to provide samples to serve as healthy controls. These subjects may or may not have been the same ones with noted ACL pathology. The concentrations of 20 biomarkers were determined using a multiplex magnetic bead immunoassay. Biomarker concentrations were then compared between the 3 study groups (ACL tears with and without cartilage injury, and uninjured contralateral knees) using an analysis of variance test with pairwise comparisons. The minimal clinically important difference was calculated based on the standard error of measurement.
  
  
  RESULTS
  The study included synovial fluid samples from 134 knees: 34 ACL tears without cartilage injury (mean age 34.0 years), 28 ACL tears with cartilage injury (mean age 36.3 years), and 72 healthy controls (mean age 41.1 years). Analysis of variance testing showed significant differences among groups for matrix metalloproteinase-3 (F = 81.8; P < .001), tissue inhibitor of metalloproteinase (TIMP)-1 (F = 7.9; P ≤ .001), TIMP-2 (F = 4.5; P = .015); fibroblast growth factor-2 (F = 4.9; P = .011), interleukin-6 (F = 8.2; P = .001), and macrophage inflammatory protein-1 beta (F = 7.3; P = .001). Pairwise comparisons showed no significant differences between ACL tears with, and without cartilage injury, but did show that both groups of ACL tears had significantly higher concentrations of (first P value = ACL tears with and then ACL tears without cartilage injury): matrix metalloproteinase-3 (P < .001; P < .001), TIMP-1 (P < .001; P = .011), interleukin-6 (P = .009; P = .038), and macrophage inflammatory protein-1 beta (P = .003; P = .045) compared with contralateral controls. ACL tears without associated cartilage damage had significantly lower concentrations of TIMP-2 (P = .011) and fibroblast growth factor-2 (P = .014) compared with controls. All biomarker concentration differences that reached statistical significance were also larger than calculated minimal clinically important differences.
  
  
  CONCLUSIONS
  The current study identified 6 pro- and anti-inflammatory synovial fluid biomarkers whose concentrations after ACL injury were significantly different compared with uninjured controls. No significant differences in synovial fluid biomarker concentrations were seen between ACL injured knees with and without associated cartilage damage.
  
  
  METHODS
  Level III, retrospective comparative study of prospectively gathered data.
authors.affiliation: Division of Sports Medicine, Department of Orthopaedic Surgery, NYU Hospital for Joint Diseases, New York, New York, U.S.A.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Kaplan
authors.affiliation: Division of Sports Medicine, Department of Orthopaedic Surgery, NYU Hospital for Joint Diseases, New York, New York, U.S.A.
authors.forename: Vanessa G
authors.initials: VG
authors.lastname: Cuellar
authors.affiliation: Division of Sports Medicine, Department of Orthopaedic Surgery, NYU Hospital for Joint Diseases, New York, New York, U.S.A.
authors.forename: Laith M
authors.initials: LM
authors.lastname: Jazrawi
authors.affiliation: Division of Sports Medicine, Department of Orthopaedic Surgery, NYU Hospital for Joint Diseases, New York, New York, U.S.A.. Electronic address: Eric.Strauss@nyumc.org.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Strauss
mesh_terms: D000328:Adult; D016118:Anterior Cruciate Ligament / Q000601:surgery; D000070598:Anterior Cruciate Ligament Injuries / Q000378:metabolism* / Q000601:surgery; D059549:Anterior Cruciate Ligament Reconstruction / Q000379:methods; D001182:Arthroscopy / Q000379:methods; D015415:Biomarkers / Q000378:metabolism*; D002358:Cartilage, Articular / Q000293:injuries; D016022:Case-Control Studies; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007718:Knee Injuries / Q000378:metabolism / Q000601:surgery; D007719:Knee Joint / Q000601:surgery; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D013582:Synovial Fluid / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism; D055815:Young Adult
chemical_list: D015415:Biomarkers; C508600:IL6 protein, human; D018836:Inflammation Mediators; D015850:Interleukin-6; C560823:TIMP2 protein, human; D016222:Fibroblast Growth Factor 2; D019716:Tissue Inhibitor of Metalloproteinase-2