title: Osteoarthritis-related biomarkers following anterior cruciate ligament injury and reconstruction: a systematic review.
abstract: OBJECTIVE
  There is an increased risk of developing knee osteoarthritis (OA) following anterior cruciate ligament (ACL) injury. Biomarkers may provide diagnostic, prognostic, or burden of disease indicators of OA before radiographic changes become apparent. Unfortunately, there has been no systematic review to clarify which biomarkers may be most informative following injury. Therefore, this review critically investigated existing studies of OA-related biomarkers in ACL-deficient (ACL-D) and reconstructed (ACL-R) patients to summarize the current evidence and identify knowledge gaps.
  
  
  METHODS
  A systematic review of the literature in Web of Science and PubMed databases (1960-June 2014) was performed. All English-language case-control and longitudinal studies assessing OA-related biomarkers in ACL-D and ACL-R patients were considered. Data regarding biomarker changes over time within ACL-D and ACL-R patients as well as differences in ACL-D/ACL-R patients compared with a control group were extracted from pertinent studies.
  
  
  RESULTS
  A descriptive summary of 20 included studies was produced. In ACL-D patients compared with controls, synovial fluid biomarkers indicated elevated collagen turnover, while the inflammatory cytokine response was inconclusive. In ACL-R patients, serum concentrations indicated decreased collagen breakdown, but urine concentrations were indicative of greater collagen breakdown when compared to controls. Compared to preoperative values, the overall inflammatory cytokine response measured with synovial fluid biomarkers increased while plasma biomarkers did not change following reconstruction.
  
  
  CONCLUSIONS
  Patients with ACL-D or ACL-R have altered biomarkers indicative of OA. More research with standardized reporting is needed to effectively determine which biomarkers are the most indicative for OA development and progression following ACL injury.
authors.affiliation: Department of Exercise and Sports Science, University of North Carolina at Chapel Hill, Chapel Hill NC, USA. Electronic address: Harkey@unc.edu.
authors.forename: M S
authors.initials: MS
authors.lastname: Harkey
authors.affiliation: Department of Exercise and Sports Science, University of North Carolina at Chapel Hill, Chapel Hill NC, USA. Electronic address: bluc@live.unc.edu.
authors.forename: B A
authors.initials: BA
authors.lastname: Luc
authors.affiliation: Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Thurston Arthritis Research Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Injury Prevention Research Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Electronic address: golight@email.unc.edu.
authors.forename: Y M
authors.initials: YM
authors.lastname: Golightly
authors.affiliation: Department of Kinesiology, University of North Carolina at Charlotte, Charlotte, NC, USA. Electronic address: afenwick@uncc.edu.
authors.forename: A C
authors.initials: AC
authors.lastname: Thomas
authors.affiliation: Division of Rheumatology, Tufts Medical Center, Boston, MA, USA. Electronic address: jeffrey.driban@tufts.edu.
authors.forename: J B
authors.initials: JB
authors.lastname: Driban
authors.affiliation: Department of Exercise and Sports Science, University of North Carolina at Chapel Hill, Chapel Hill NC, USA; Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Electronic address: ach@email.unc.edu.
authors.forename: A C
authors.initials: AC
authors.lastname: Hackney
authors.affiliation: Department of Exercise and Sports Science, University of North Carolina at Chapel Hill, Chapel Hill NC, USA. Electronic address: brian@unc.edu.
authors.forename: B
authors.initials: B
authors.lastname: Pietrosimone
mesh_terms: D016118:Anterior Cruciate Ligament / Q000601:surgery*; D000070598:Anterior Cruciate Ligament Injuries; D059549:Anterior Cruciate Ligament Reconstruction; D015415:Biomarkers / Q000032:analysis; D016022:Case-Control Studies; D006801:Humans; D020370:Osteoarthritis, Knee / Q000175:diagnosis*; D011183:Postoperative Complications / Q000175:diagnosis*
chemical_list: D015415:Biomarkers
keywords: Cartilage; Collagen; Inflammation; Joint metabolism; Knee injury; Osteoarthritis