title: What Are the Prognostic Factors for Radiographic Progression of Knee Osteoarthritis? A Meta-analysis.
abstract: BACKGROUND
  A previous systematic review on prognostic factors for knee osteoarthritis (OA) progression showed associations for generalized OA and hyaluronic acid levels. Knee pain, radiographic severity, sex, quadriceps strength, knee injury, and regular sport activities were not associated. It has been a decade since the literature search of that review and many studies have been performed since then investigating prognostic factors for radiographic knee OA progression.
  
  
  OBJECTIVE
  The purpose of this study is to provide an updated systematic review of available evidence regarding prognostic factors for radiographic knee OA progression.
  
  
  METHODS
  We searched for observational studies in MEDLINE and EMBASE. Key words were: knee, osteoarthritis (or arthritis, or arthrosis, or degenerative joint disease), progression (or prognosis, or precipitate, or predictive), and case-control (or cohort, or longitudinal, or follow-up). Studies fulfilling the inclusion criteria were assessed for methodologic quality according to established criteria for reviews on prognostic factors in musculoskeletal disorders. Data were extracted and results were pooled if possible or summarized according to a best-evidence synthesis. A total of 1912 additional articles were identified; 43 met our inclusion criteria. The previous review contained 36 articles, thus providing a new total of 79 articles. Seventy-two of the included articles were scored high quality, the remaining seven were low quality.
  
  
  RESULTS
  The pooled odds ratio (OR) of two determinants showed associations with knee OA progression: baseline knee pain (OR, 2.38 [95% CI, 1.74-3.27) and Heberden nodes (OR, 2.66 [95% CI, 1.46-8.84]). Our best-evidence synthesis showed strong evidence that varus alignment, serum hyaluronic acid, and tumor necrosis factor-α are associated with knee OA progression. There is strong evidence that sex, former knee injury, quadriceps strength, smoking, running, and regular performance of sports are not associated with knee OA progression. Evidence for the majority of determined associations, however, was limited, conflicting, or inconclusive.
  
  
  CONCLUSIONS
  Baseline knee pain, presence of Heberden nodes, varus alignment, and high levels of serum markers hyaluronic acid and tumor necrosis factor-α predict knee OA progression. Sex, knee injury, and quadriceps strength, among others, did not predict knee OA progression. Large variation remains in definitions of knee OA and knee OA progression. Clinical studies should use more consistent definitions of these factors to facilitate data pooling by future meta-analyses.
authors.affiliation: Department of General Practice, Erasmus MC, University Medical Center Rotterdam, Room NA-1923, PO Box 2040, 3000 CA, Rotterdam, The Netherlands, a.bastick@erasmusmc.nl.
authors.forename: Alex N
authors.initials: AN
authors.lastname: Bastick
authors.forename: Janneke N
authors.initials: JN
authors.lastname: Belo
authors.forename: Jos
authors.initials: J
authors.lastname: Runhaar
authors.forename: Sita M A
authors.initials: SM
authors.lastname: Bierma-Zeinstra
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018771:Arthralgia / Q000175:diagnosis / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood; D016009:Chi-Square Distribution; D018450:Disease Progression; D005260:Female; D006801:Humans; D006820:Hyaluronic Acid / Q000097:blood; D007719:Knee Joint / Q000000981:diagnostic imaging* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020370:Osteoarthritis, Knee / Q000097:blood / Q000000981:diagnostic imaging* / Q000503:physiopathology; D010147:Pain Measurement; D011237:Predictive Value of Tests; D011379:Prognosis; D011859:Radiography; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D015415:Biomarkers; D014409:Tumor Necrosis Factor-alpha; D006820:Hyaluronic Acid