title: A novel method for bone area measurement provides new insights into osteoarthritis and its progression.
abstract: BACKGROUND
  Modern image analysis enables the accurate quantification of knee osteoarthritis (OA) bone using MRI. We hypothesised that three-dimensional changes in bone would be characteristic of OA and provide a responsive measure of progression.
  
  
  METHODS
  1312 participants with radiographic knee OA, and 885 non-OA controls with MRIs at baseline, 1, 2 and 4 years were selected from the NIH Osteoarthritis Initiative. Automated segmentation of all knee bones and calculation of bone area was performed using active appearance models. In a subset of 352 participants, responsiveness of bone area change was compared with change in radiographic joint space width (JSW) and MRI cartilage thickness over a 2-year period.
  
  
  RESULTS
  All OA knee compartments showed increased bone area over time compared with non-OA participants: for example, the 4-year percentage change from baseline in medial femur area for OA (95% CI) was 1.87(0.13), non-OA 0.43 (0.07); p<0.0001. Bone area change was more responsive than cartilage thickness or JSW; 2-year SRM for bone area in the medial femur was 0.83, for the most responsive cartilage thickness measure central medial femorotibial composite (cMFTC): 0.38, JSW: 0.35. Almost half of all knees had change greater than smallest detectable difference at 2 years. Body mass index, gender and alignment had only a small effect on the rate of change of bone area.
  
  
  CONCLUSIONS
  Changes in bone area discriminated people with OA from controls and was more responsive than the current and impending standards for assessing OA progression. The shape change in OA bone provides a new window on OA pathogenesis and a focus for clinical trials.
authors.affiliation: Imorphics Ltd, Manchester Science Park, Manchester, UK.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Bowes
authors.affiliation: Imorphics Ltd, Manchester Science Park, Manchester, UK.
authors.forename: Graham R
authors.initials: GR
authors.lastname: Vincent
authors.affiliation: Imorphics Ltd, Manchester Science Park, Manchester, UK.
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Wolstenholme
authors.affiliation: NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK.
authors.forename: Philip G
authors.initials: PG
authors.lastname: Conaghan
mesh_terms: D000368:Aged; D002358:Cartilage, Articular / Q000473:pathology*; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D005269:Femur / Q000473:pathology*; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009929:Organ Size; D020370:Osteoarthritis, Knee / Q000473:pathology*; D010329:Patella / Q000473:pathology*; D011446:Prospective Studies; D013977:Tibia / Q000473:pathology*
keywords: Disease Activity; Knee Osteoarthritis; Magnetic Resonance Imaging