title: Serum and urinary biochemical markers for knee and hip-osteoarthritis: a systematic review applying the consensus BIPED criteria.
abstract: BACKGROUND
  Molecules that are released into biological fluids during matrix metabolism of articular cartilage, subchondral bone, and synovial tissue could serve as biochemical markers of the process of osteoarthritis (OA). Unfortunately, actual breakthroughs in the biochemical OA marker field are limited so far.
  
  
  OBJECTIVE
  By reviewing the status of commercially available biochemical OA markers according to the "Burden of disease, Investigative, Prognostic, Efficacy of intervention, and Diagnostic" ("BIPED") classification, future use of this "BIPED" classification is encouraged and more efficient biochemical OA marker research stimulated.
  
  
  METHODS
  Three electronic databases [PubMed, Scopus, EMBASE (1997-May 2009)] were searched for publications on blood and urinary biochemical markers in human primary knee and hip-OA.
  
  
  METHODS
  Stepwise selection of original English publications describing human studies on blood or urinary biochemical markers in primary knee or hip-OA was performed. Selected articles were fully read to determine whether biochemical markers were investigated on performance within any of the "BIPED" categories. Eighty-four relevant publications were identified.
  
  
  METHODS
  Data from relevant publications were tabulated according to the "BIPED" classification. Individual analyses within a publication were summarized in general "BIPED" scores.
  
  
  RESULTS
  An uneven distribution of scores on biochemical marker performance and heterogeneity among the publications complicated direct comparison of individual biochemical markers. Comparison of categories of biochemical markers was therefore performed instead. In general, biochemical markers of cartilage degradation were investigated most extensively and performed well in comparison with other categories of biochemical markers. Biochemical markers of bone metabolism performed less adequately. Biochemical markers of synovial tissue metabolism were not investigated extensively, but performed quite well.
  
  
  CONCLUSIONS
  Specific biochemical markers and categories of biochemical markers as well as their nature, origin and metabolism, need further investigation. International standardization of future investigations should be pursued to obtain more high-quality, homogenous data on the full spectrum of biochemical OA markers.
authors.affiliation: Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, P.O. Box 95500, 3508 GA Utrecht, The Netherlands. w.e.vanspil@umcutrecht.nl
authors.forename: W E
authors.initials: WE
authors.lastname: van Spil
authors.forename: J
authors.initials: J
authors.lastname: DeGroot
authors.forename: W F
authors.initials: WF
authors.lastname: Lems
authors.forename: J C M
authors.initials: JC
authors.lastname: Oostveen
authors.forename: F P J G
authors.initials: FP
authors.lastname: Lafeber
mesh_terms: D015415:Biomarkers / Q000097:blood / Q000652:urine; D001842:Bone and Bones / Q000378:metabolism; D002358:Cartilage, Articular / Q000378:metabolism; D017281:Cost of Illness; D006801:Humans; D015207:Osteoarthritis, Hip / Q000175:diagnosis*; D020370:Osteoarthritis, Knee / Q000175:diagnosis*; D011379:Prognosis; D013583:Synovial Membrane / Q000378:metabolism
chemical_list: D015415:Biomarkers