title: Is there a causal link between knee loading and knee osteoarthritis progression? A systematic review and meta-analysis of cohort studies and randomised trials.
abstract: OBJECTIVE
  We performed a systematic review, meta-analysis and assessed the evidence supporting a causal link between knee joint loading during walking and structural knee osteoarthritis (OA) progression.
  
  
  METHODS
  Systematic review, meta-analysis and application of Bradford Hill's considerations on causation.
  
  
  METHODS
  We searched MEDLINE, Scopus, AMED, CINAHL and SportsDiscus for prospective cohort studies and randomised controlled trials (RCTs) from 1950 through October 2013.
  
  
  METHODS
  We selected cohort studies and RCTs in which estimates of knee joint loading during walking were used to predict structural knee OA progression assessed by X-ray or MRI.
  
  
  METHODS
  Meta-analysis was performed to estimate the combined OR for structural disease progression with higher baseline loading. The likelihood of a causal link between knee joint loading and OA progression was assessed from cohort studies using the Bradford Hill guidelines to derive a 0-4 causation score based on four criteria and examined for confirmation in RCTs.
  
  
  RESULTS
  Of the 1078 potentially eligible articles, 5 prospective cohort studies were included. The studies included a total of 452 patients relating joint loading to disease progression over 12-72 months. There were very serious limitations associated with the methodological quality of the included studies. The combined OR for disease progression was 1.90 (95% CI 0.85 to 4.25; I(2)=77%) for each one-unit increment in baseline knee loading. The combined causation score was 0, indicating no causal association between knee loading and knee OA progression. No RCTs were found to confirm or refute the findings from the cohort studies.
  
  
  CONCLUSIONS
  There is very limited and low-quality evidence to support for a causal link between knee joint loading during walking and structural progression of knee OA.
  
  
  BACKGROUND
  CRD42012003253.
authors.affiliation: The Parker Institute, Copenhagen University Hospitals Bispebjerg and Frederiksberg, Copenhagen, Denmark.
authors.forename: Marius
authors.initials: M
authors.lastname: Henriksen
authors.affiliation: School of Exercise Science, Australian Catholic University, Brisbane, Queensland, Australia.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Creaby
authors.affiliation: Faculty of Health Sciences, Institute of Sports Science and Clinical Biomechanics, University of Southern Denmark, Odense, Denmark.
authors.forename: Hans
authors.initials: H
authors.lastname: Lund
authors.affiliation: Faculty of Health Sciences, Institute of Sports Science and Clinical Biomechanics, University of Southern Denmark, Odense, Denmark Department of Rheumatology and Gerontology, Copenhagen University Hospital Gentofte, Copenhagen, Denmark.
authors.forename: Carsten
authors.initials: C
authors.lastname: Juhl
authors.affiliation: The Parker Institute, Copenhagen University Hospitals Bispebjerg and Frederiksberg, Copenhagen, Denmark Faculty of Health Sciences, Institute of Sports Science and Clinical Biomechanics, University of Southern Denmark, Odense, Denmark.
authors.forename: Robin
authors.initials: R
authors.lastname: Christensen
mesh_terms: D015331:Cohort Studies; D018450:Disease Progression; D006801:Humans; D007719:Knee Joint; D020370:Osteoarthritis, Knee / Q000209:etiology*; D016032:Randomized Controlled Trials as Topic; D016474:Weight-Bearing
keywords: EPIDEMIOLOGY; RHEUMATOLOGY; STATISTICS & RESEARCH METHODS