title: Location-independent analysis of structural progression of osteoarthritis-Taking it all apart, and putting the puzzle back together makes the difference.
abstract: The metric accepted by regulatory bodies for determining structural progression in clinical trials of knee osteoarthritis (OA) remains change in radiographic joint space width in the medial femorotibial compartment. However, magnetic resonance imaging has revealed that cartilage loss is spatially heterogeneous, and that it is enigmatic which knee will lose cartilage at which location. Whereas previous reviews have focused on imaging in general, the purpose of this particular perspective is to highlight availability and applications of location-independent analysis methodology in measuring structural progression in epidemiological and interventional clinical trials, and to highlight its specific advantages over existing methodologies.
  
  
  
  Narrative review/perspective based on a Pubmed search of original articles from 2009 to current.
  
  
  
  Ordering longitudinal change in subregion cartilage thickness by magnitude and direction, and averaging such ordered values or sums of negative and positive changes across knees is shown to be superior in detecting risk factors and interventional effects on structural progression of knee OA. Further, the methodology permits exploration of cartilage loss and gain simultaneously, phenomena that are missed when measurements are confined to cartilage volume or thickness loss in plates or compartments.
  
  
  
  Given spatial heterogeneity of cartilage loss in knee OA, location-independent analysis by MRI may provide opportunity for a paradigm shift. The authors recommend use of a location-independent metrices as the structural endpoints in epidemiological and intervention trials, particularly when examining anabolic and catabolic drug effects. Location-independent methods may be translated to analysis of cartilage composition and other articular tissues.
authors.affiliation: Institute of Anatomy, Paracelsus Medical University Salzburg & Nuremberg, Strubergasse 21, A-5020 Salzburg, Austria; Chondrometrics GmbH, Ainring, Germany. Electronic address: felix.eckstein@pmu.ac.at.
authors.forename: Felix
authors.initials: F
authors.lastname: Eckstein
authors.affiliation: StatAnswers Consulting LLC, Minneapolis, MN.
authors.forename: Robert
authors.initials: R
authors.lastname: Buck
authors.affiliation: Institute of Anatomy, Paracelsus Medical University Salzburg & Nuremberg, Strubergasse 21, A-5020 Salzburg, Austria; Chondrometrics GmbH, Ainring, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wirth
mesh_terms: D002358:Cartilage, Articular / Q000000981:diagnostic imaging*; D018450:Disease Progression; D006801:Humans; D008279:Magnetic Resonance Imaging; D020370:Osteoarthritis, Knee / Q000000981:diagnostic imaging*
keywords: Clinical Trial; DMOAD; Magnetic resonance imaging; Osteoarthritis; Structural progression