title: Does statin use have a disease modifying effect in symptomatic knee osteoarthritis? Study protocol for a randomised controlled trial.
abstract: BACKGROUND
  Osteoarthritis (OA) is a major clinical and public health problem, with no current medications approved as having disease modifying effects. HMG-CoA reductase inhibitors, or "statins", a drug class widely used to prevent cardiovascular events, could potentially affect OA progression via a number of mechanisms including their effects on lipid metabolism and inflammation. The aim of this multicentre, randomised, double-blind, placebo-controlled trial is to determine whether atorvastatin reduces the progression of knee structural changes and symptoms over 2 years in patients with symptomatic knee OA.
  
  
  METHODS
  350 patients with symptomatic knee OA will be recruited through the OA Clinical Trial Network (in Melbourne, Hobart and Adelaide). They will be randomly allocated to the two arms of the study, receiving either 40 mg of atorvastatin or identical placebo once daily for 2 years. Magnetic resonance imaging of the knee will be performed at baseline and 2 years later. Knee structure, symptoms and function will be assessed using validated methods. The primary outcome is annual percentage change in knee cartilage volume. Secondary outcomes include progression of cartilage defects, bone marrow lesions, knee pain and function. The primary analysis will be by intention to treat, but per protocol analyses will also be performed.
  
  
  CONCLUSIONS
  The study will provide high-quality evidence to address whether atorvastatin has a novel disease modifying effect in OA by delaying the structural and symptomatic progression of knee OA. Thus, the trial has major public health and clinical importance, as if found to be beneficial, atorvastatin could produce substantial cost savings by delaying and possibly reducing the need for joint replacement surgery, and provide marked improvements in quality of life for people with OA.
  
  
  BACKGROUND
  Australian New Zealand Clinical Trials Registry: ACTRN12613000190707 , registered on 18 February 2013.
authors.affiliation: Department of Epidemiology and Preventive Medicine, Monash University, Alfred Hospital, Melbourne, 3004, Australia. yuanyuan.wang@monash.edu.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Epidemiology and Preventive Medicine, Monash University, Alfred Hospital, Melbourne, 3004, Australia. andrew.tonkin@monash.edu.
authors.forename: Andrew
authors.initials: A
authors.lastname: Tonkin
authors.affiliation: Menzies Institute for Medical Research, University of Tasmania, Private Bag 23, Hobart, TAS, 7000, Australia. graeme.jones@utas.edu.au.
authors.forename: Graeme
authors.initials: G
authors.lastname: Jones
authors.affiliation: The Queen Elizabeth Hospital, University of Adelaide, Woodville, SA, 5011, Australia. Catherine.Hill@health.sa.gov.au.|Discipline of Medicine, University of Adelaide, Adelaide, SA, 5005, Australia. Catherine.Hill@health.sa.gov.au.
authors.forename: Catherine
authors.initials: C
authors.lastname: Hill
authors.affiliation: Department of Epidemiology and Preventive Medicine, Monash University, Alfred Hospital, Melbourne, 3004, Australia. Changhai.Ding@utas.edu.au.|Menzies Institute for Medical Research, University of Tasmania, Private Bag 23, Hobart, TAS, 7000, Australia. Changhai.Ding@utas.edu.au.
authors.forename: Changhai
authors.initials: C
authors.lastname: Ding
authors.affiliation: Department of Epidemiology and Preventive Medicine, Monash University, Alfred Hospital, Melbourne, 3004, Australia. anita.wluka@monash.edu.
authors.forename: Anita E
authors.initials: AE
authors.lastname: Wluka
authors.affiliation: Department of Epidemiology and Preventive Medicine, Monash University, Alfred Hospital, Melbourne, 3004, Australia. andrew.forbes@monash.edu.
authors.forename: Andrew
authors.initials: A
authors.lastname: Forbes
authors.affiliation: Department of Epidemiology and Preventive Medicine, Monash University, Alfred Hospital, Melbourne, 3004, Australia. Flavia.Cicuttini@monash.edu.
authors.forename: Flavia M
authors.initials: FM
authors.lastname: Cicuttini
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000069059:Atorvastatin / Q000009:adverse effects / Q000627:therapeutic use*; D001315:Australia; D001696:Biomechanical Phenomena; D002358:Cartilage, Articular / Q000187:drug effects / Q000473:pathology; D002985:Clinical Protocols; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D057194:Intention to Treat Analysis; D007719:Knee Joint / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D020127:Recovery of Function; D012107:Research Design; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000069059:Atorvastatin