title: The association between changes in synovial fluid levels of ARGS-aggrecan fragments, progression of radiographic osteoarthritis and self-reported outcomes: a cohort study.
abstract: OBJECTIVE
  To investigate whether change in concentrations over time of aggrecanase generated ARGS-aggrecan in synovial fluid (SF ARGS) associates with progression of radiographic knee osteoarthritis (OA) and patient-reported outcome in subjects with previous meniscectomy.
  
  
  METHODS
  We studied 141 subjects at two time points after meniscectomy. Time point A was on average 18 years after meniscectomy, time point B was on average 7.5 years later; 74 subjects had SF available from both examinations. We measured SF ARGS by an electrochemiluminescence immunoassay, graded radiographic features of tibiofemoral or patellofemoral OA according to the Osteoarthritis Research Society International (OARSI) atlas, and scored patient-reported outcomes using the Knee Injury and Osteoarthritis Outcome Score (KOOS). Using logistic regression (adjusted for age, gender, body mass index, time between examinations, and SF ARGS at first examination) we assessed associations between change in SF ARGS between first and second examinations and progression of radiographic OA and KOOS.
  
  
  RESULTS
  In subjects with decreasing SF ARGS between examinations, the likelihood of loss of joint space and worsening of KOOS pain between examinations was increased 6- and 4-fold respectively compared to those increasing in SF ARGS (odds ratio (OR) 5.72; 95% confidence interval (CI) 1.53-21.4 and 3.66; 1.01-13.2, respectively). No significant associations were seen between decreasing SF ARGS and progression of osteophytes (OR 0.88; 0.28-2.78), or for patient-reported outcomes other than KOOS pain.
  
  
  CONCLUSIONS
  Having decreasing levels of SF ARGS over time was associated with an increased risk of loss of joint space and pain worsening, but showed no association with other patient-reported outcomes or osteophyte progression.
authors.affiliation: Department of Orthopaedics, Clinical Sciences Lund, Lund University, Lund, Sweden. Electronic address: staffan.larsson@med.lu.se.
authors.forename: S
authors.initials: S
authors.lastname: Larsson
authors.affiliation: Department of Orthopaedics, Clinical Sciences Lund, Lund University, Lund, Sweden; Clinical Epidemiology Research & Training Unit, Boston University School of Medicine, Boston, MA, USA. Electronic address: martin.englund@med.lu.se.
authors.forename: M
authors.initials: M
authors.lastname: Englund
authors.affiliation: Department of Orthopaedics, Clinical Sciences Lund, Lund University, Lund, Sweden. Electronic address: andre.struglics@med.lu.se.
authors.forename: A
authors.initials: A
authors.lastname: Struglics
authors.affiliation: Department of Orthopaedics, Clinical Sciences Lund, Lund University, Lund, Sweden; Research Unit for Musculoskeletal Function and Physiotherapy, University of Southern Denmark, Denmark; Department of Orthopaedics and Traumatology, University of Southern Denmark, Denmark. Electronic address: stefan.lohmander@med.lu.se.
authors.forename: L S
authors.initials: LS
authors.lastname: Lohmander
mesh_terms: D000328:Adult; D000368:Aged; D053674:Aggrecans / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D015331:Cohort Studies; D018450:Disease Progression; D010450:Endopeptidases / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007718:Knee Injuries / Q000150:complications / Q000601:surgery; D008297:Male; D008592:Menisci, Tibial / Q000601:surgery; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000000981:diagnostic imaging / Q000209:etiology / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism; D011184:Postoperative Period; D011379:Prognosis; D011859:Radiography; D012737:Sex Factors; D013582:Synovial Fluid / Q000378:metabolism*
chemical_list: D053674:Aggrecans; D015415:Biomarkers; D010446:Peptide Fragments; D010450:Endopeptidases; C083641:aggrecanase