title: Development and reliability of a multi-modality scoring system for evaluation of disease progression in pre-clinical models of osteoarthritis: celecoxib may possess disease-modifying properties.
abstract: OBJECTIVE
  We sought to develop a comprehensive scoring system for evaluation of pre-clinical models of osteoarthritis (OA) progression, and use this to evaluate two different classes of drugs for management of OA.
  
  
  METHODS
  Post-traumatic OA (PTOA) was surgically induced in skeletally mature rats. Rats were randomly divided in three groups receiving either glucosamine (high dose of 192 mg/kg) or celecoxib (clinical dose) or no treatment. Disease progression was monitored utilizing micro-magnetic resonance imaging (MRI), micro-computed tomography (CT) and histology. Pertinent features such as osteophytes, subchondral sclerosis, joint effusion, bone marrow lesion (BML), cysts, loose bodies and cartilage abnormalities were included in designing a sensitive multi-modality based scoring system, termed the rat arthritis knee scoring system (RAKSS).
  
  
  RESULTS
  Overall, an inter-observer correlation coefficient (ICC) of greater than 0.750 was achieved for each scored feature. None of the treatments prevented cartilage loss, synovitis, joint effusion, or sclerosis. However, celecoxib significantly reduced osteophyte development compared to placebo. Although signs of inflammation such as synovitis and joint effusion were readily identified at 4 weeks post-operation, we did not detect any BML.
  
  
  CONCLUSIONS
  We report the development of a sensitive and reliable multi-modality scoring system, the RAKSS, for evaluation of OA severity in pre-clinical animal models. Using this scoring system, we found that celecoxib prevented enlargement of osteophytes in this animal model of PTOA, and thus it may be useful in preventing OA progression. However, it did not show any chondroprotective effect using the recommended dose. In contrast, high dose glucosamine had no measurable effects.
authors.affiliation: Faculty of Pharmacy & Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada. Electronic address: a.panahifar@ualberta.ca.
authors.forename: A
authors.initials: A
authors.lastname: Panahifar
authors.affiliation: Department of Radiology & Diagnostic Imaging, University of Alberta, Edmonton, Alberta, Canada. Electronic address: jjaremko@ualberta.ca.
authors.forename: J L
authors.initials: JL
authors.lastname: Jaremko
authors.affiliation: Department of Medical Physics, Cross Cancer Institute, University of Alberta, Edmonton, Alberta, Canada. Electronic address: Anthony.tessier@albertahealthservices.ca.
authors.forename: A G
authors.initials: AG
authors.lastname: Tessier
authors.affiliation: Department of Radiology & Diagnostic Imaging, University of Alberta, Edmonton, Alberta, Canada. Electronic address: rlambert@ualberta.ca.
authors.forename: R G
authors.initials: RG
authors.lastname: Lambert
authors.affiliation: Department of Rheumatology, University of Alberta, Edmonton, Alberta, Canada. Electronic address: walter.maksymowych@ualberta.ca.
authors.forename: W P
authors.initials: WP
authors.lastname: Maksymowych
authors.affiliation: Department of Medical Physics, Cross Cancer Institute, University of Alberta, Edmonton, Alberta, Canada; Department of Oncology, University of Alberta, Edmonton, Alberta, Canada; Department of Physics, University of Alberta, Edmonton, Alberta, Canada. Electronic address: bfallone@ualberta.ca.
authors.forename: B G
authors.initials: BG
authors.lastname: Fallone
authors.affiliation: Faculty of Pharmacy & Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada; Department of Biomedical Engineering, University of Alberta, Edmonton, Alberta, Canada. Electronic address: mdoschak@ualberta.ca.
authors.forename: M R
authors.initials: MR
authors.lastname: Doschak
mesh_terms: D000818:Animals; D016118:Anterior Cruciate Ligament / Q000601:surgery; D001845:Bone Cysts / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology; D001855:Bone Marrow Diseases / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology; D002358:Cartilage, Articular / Q000000981:diagnostic imaging / Q000473:pathology; D000068579:Celecoxib; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use*; D004195:Disease Models, Animal; D018450:Disease Progression; D005944:Glucosamine / Q000627:therapeutic use; D007718:Knee Injuries; D008279:Magnetic Resonance Imaging; D020370:Osteoarthritis, Knee / Q000175:diagnosis* / Q000188:drug therapy* / Q000209:etiology; D054850:Osteophyte / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology; D011720:Pyrazoles / Q000627:therapeutic use*; D051381:Rats; D015203:Reproducibility of Results; D012720:Severity of Illness Index; D013449:Sulfonamides / Q000627:therapeutic use*; D013585:Synovitis / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology; D055114:X-Ray Microtomography
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D000068579:Celecoxib; D005944:Glucosamine
keywords: CT; Celecoxib; Glucosamine; MRI; Osteoarthritis; Osteophytes