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Table 4 Disease characteristics studied as determinants for clinical knee OA progression in the included studies

From: Prognostic factors for progression of clinical osteoarthritis of the knee: a systematic review of observational studies

Determinant Author [ref.] year Analysis of determinant Definition of knee OA progression OR/RR/HR/β (95 % CI) Association with OA prognosis*
Severity      
Radiographic Bruyere [13] 2005 JSN ≥0.5 mm/3 years Knee joint surgery RR 4.61 (1.65–12.8) +
(N = 8,201) Riddle [30] 2012 Per grade (0–4 grade scale) Knee joint surgery RR 2.09 (1.63–2.69) +
  Collins [15] 2014 K/L 3 vs K/L 2a Severe vs no pain WOMAC pain trajectory OR 4.3 (2.1–8.6) +
  Holla [21] 2014 Osteophytosis Poor vs good outcome WOMAC-PF trajectory OR 5.68 (2.57–12.55) +
  Oak [26] 2013 Baseline JSW (mm) Decrease KOOS pain (KOOS symptom and quality of life show similar regression coefficients) β 1.94 (1.19–2.69) +
   JSN over 4 years (mm) β 2.31 (1.18–3.44) +
Clinical Alschuler [9] 2013 NRS of past 7 daysa ≥20 % change in combined NRS and WOMAC-PF score Not provided +
(N = 7,558)   WOMAC-PFa   Not provided +
  Holla [21] 2014 NRS for knee paina Poor vs good outcome WOMAC-PF trajectory OR 1.81 (1.51–2.16) +
  Oak [26] 2013 Baseline KOOS value Decrease KOOS pain (KOOS symptom and quality of life show similar regression coefficients) β 0.49 (0.43–0.59) +
  Pisters [27] 2012 Per cm increase VASa Increase in self-reported limitations (WOMAC-PF) β 5.99 (2.90–12.4) +
  Sharma [34] 2003 Per 20 mm VAS increase Progressing/remaining in poor WOMAC-PF quintiles OR 1.48 (1.12–1.95) +
  Riddle [30] 2012 NRS of past 30 daysa Knee joint surgery RR 1.12 (1.02–1.22) +
Painful knee flexion Riddle [30] 2012 Yes vs no Knee joint surgery RR 1.58 (1.04–2.39) +
(N = 4,670)      
Joint line tenderness Holla [21] 2014 Yes vs no Poor vs good outcome WOMAC-PF trajectory OR 2.63 (1.38–5.02) +
(N = 5,367) Riddle [30] 2012 Yes vs no Knee joint surgery RR 0.71 (0.43–1.18) o
Flexion contracture Riddle [30] 2012 Knee flexion contracture (°) Knee joint surgery RR 1.06 (1.02–1.11) +
(N = 4,670)      
Knee ROM Holla [21] 2014 Active ROM in degrees Poos vs good outcome WOMAC-PF trajectory OR 0.96 (0.93–1.00)
(N = 913) Pisters [27] 2012 Mean extension Increase in performance-based limitations (TWT) β 0.92 (0.86–0.98)
Hand grip strength (muscle strength) Muraki [25] 2012 Per 1 kg strength increase Incident knee pain at follow-up (baseline K/L ≥2) OR 1.00 (0.98–1.02) o
(N = 1,313)      
Quadriceps strength Amin [10] 2009 Low vs middle Increase in knee specific VAS pain score Not provided o
(N = 5,151)   vs high strength Increase in self-reported limitations (WOMAC-PF) Not provided o
  Pisters [27] 2012 Continuous in Newton/kg Increase in self-reported limitations (WOMAC-PF) β 0.11 (0.01–1.36) o
    Increase in performance-based limitations (TWT) β 0.60 (0.37–1.03) o
  Riddle [30] 2012 Normalized to bodyweight Knee joint surgery RR 0.79 (0.65–0.96)
Bone marrow lesions/edema (BMLs/BME) Roemer [32] 2014 ≥2 subregions vs 0–1 Knee joint surgery OR 4.00 (1.75–9.16) +
  Grade ≥1 vs grade 0   OR 4.00 (0.85–18.84) o
Scher [33] 2008 Global BME vs none Knee joint surgery OR 15.2 (2.38–97.1) +
(N = 580) Tanamas [35] 2010 BMLs, present vs absent Knee joint surgery OR 1.57 (1.04–2.35) +
   Medial BMLs vs absent Knee joint surgery OR 1.78 (1.16–2.74) +
   Lateral BMLs vs absent Knee joint surgery OR 0.82 (0.43–1.54) o
Subchondral bone cysts (MRI) Tanamas [36] 2010 Medial, per grade of severity Knee joint surgery OR 1.99 (1.01–3.90) +
  Lateral, per grade of severity Knee joint surgery OR 0.96 (0.48–1.94) o
(N = 109)      
Cartilage loss (MRI) Cicuttini [14] 2004 Rate 3–8 % per annum Knee joint surgery OR 2.3 (0.4–12.2) o
(N = 681)   Rate >8 % per annum   OR 7.1 (1.4–36.5) +
  Eckstein [17] 2013 Change in cMFTC.ThC Knee joint surgery Not provided +
   Change in MFTC.ThC Not provided +
   Change in LFTC.ThC Not provided o
  Roemer [32] 2014b Grade 3 vs <3 (whole knee)   OR 4.00 (2.23–7.18) +
   Grade 3 vs 0 (MFTC) Knee joint surgery OR 3.01 (1.52–5.95) +
   Grade 3 vs 0 (LFTC)   OR 1.69 (0.94–3.02) o
  Scher [33] 2008 ≥50 % vs <50 % loss Knee joint surgery OR 2.06 (0.74–5.70) o
Meniscal extrusion (MRI) Roemer [32] 2014 ≥5 mm vs <5 mm (medial) Knee joint surgery OR 1.00 (0.60–1.67) o
  ≥5 mm vs <5 mm (lateral)   OR 1.42 (0.54–3.75) o
(N = 398)      
Meniscal damage (MRI) Roemer [32] 2014 Grade 6–8 vs 0–1 (medial) Knee joint surgery OR 1.84 (1.13–2.99) o
(N = 398)   Grade 6–8 vs 0–1 (lateral)   OR 1.10 (0.68–1.77) o
Anterior cruciate ligament tear Amin [11] 2008 Complete tear on MRI Increase in knee-specific VAS pain score Not provided o
  Complete tear on MRI Increase in self-reported limitations (WOMAC-PF) Not provided o
(N = 265)      
Synovitis Roemer [32] 2014 Infrapatellar fat pad on MRI Knee joint surgery OR 2.17 (1.33–3.56) +
(N = 764) Hill [19] 2007 Infrapatellar fat pad on MRI Increase in knee-specific VAS pain score β 4.89 (0.42–9.36) +
   Intercondylar on MRI β 5.74 (0.34–11.14) +
   Suprapatellar on MRI   β 3.35 (–0.34 to 7.05) o
  Conaghan [16] 2010 Present on US Knee joint surgery HR 1.54 (0.95–2.50) o
Joint effusion Conaghan [16] 2010 Present on US Knee joint surgery HR 3.06 (2.00–4.69) +
(N = 5,979) Riddle [29] 2009 Positive bulge sign Knee joint surgery OR 2.53 (1.13–5.56) +
  Riddle [30] 2012 Positive bulge sign Knee joint surgery RR 1.58 (1.04–2.40) +
  Roemer [32] 2014 Present on MRI (grade 1–3) Knee joint surgery OR 4.75 (2.55–8.85) +
Trabecular bone texture Podsiadlo [28] 2014 FDmean on FSA, medial Knee joint surgery OR 0.23 (0.06–0.82) +
(N = 114)   FDmean on FSA, lateral   OR 0.33 (0.09–1.22) o
C2C (serum) Berry [12] 2009 High level vs low Knee joint surgery OR 1.01 (0.94–1.08) o
(N = 117)      
COMP (serum) Berry [12] 2010 High level vs low Knee joint surgery OR 0.77 (0.15–3.81) o
(N = 117)      
PIIANP (serum) Berry [12] 2010 Natural log baseline levels Knee joint surgery OR 0.28 (0.10–0.93)
(N = 117)      
ARGS (synovial) Larsson [23] 2012 Baseline level ARGS > follow-up level ARGS ≥10 units progression KOOS Pain OR 3.66 (1.01–13.2) +
(N = 74) ≥10 units progression KOOS Function of daily living OR 1.11 (0.26–4.80) o
  1. *Statistically significant association of the determinant with OA progression: + positive association, – negative association, o no association (adjusted for age and sex if applicable). aAssessed at baseline. bSimilar results found when measuring compartment cartilage thickness. ARGS aggrecan neoepitope amino acid sequence, β regression coefficient, CI confidence interval, (c)MFTC.ThC (central) medial femorotibial compartment cartilage thickness (in mm), FD mean mean fractal dimension, FSA fractal signal analysis, C2C collagen type-II cleavage, COMP cartilage oligomeric matrix protein, HR hazard ratio, JSN joint space narrowing, JSW joint space width, K/L Kellgren and Lawrence score, KOOS Knee Injury and Osteoarthritis Outcome Score, LFTC lateral FTC, N combined sample size, MRI magnetic resonance imaging, NRS Numeric Rating Scale, OA osteoarthritis, OR odds ratio, PIIANP N-propeptide of type IIA collagen, ROM range of motion, RR relative risk, TWT Timed Walking Test, US ultrasonography, VAS Visual Analogue Scale, WOMAC-PF physical function scale of the Western Ontario and McMaster osteoarthritis index