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

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 2^a

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 days^a

≥20 % change in combined NRS and WOMAC-PF score

Not provided

+

(N = 7,558)

WOMAC-PF^a

Not provided

+

Holla [21] 2014

NRS for knee pain^a

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 VAS^a

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 days^a

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] 2014^b

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

FD_mean on FSA, medial

Knee joint surgery

OR 0.23 (0.06–0.82)

+

(N = 114)

FD_mean 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