Table 1 Knee structural associations by feature and quality grade

Felson 2003 [70]

Baseline presence of BML in medial or lateral TFJ (C)

OARSI JSN grade progression of TFJ (L)

Age, sex, and BMI

NR

OR 6.5,

+

High (83)

95 % CI 3.0 to 14.0

Dore 2010 [124]

Baseline semi-quantitative MRI BML size (C) TFJ

Incident TKR over 5 years (L)

Age, sex, BMI, knee baseline pain, leg strength, cartilage defects, tibial bone area, ROA

OR (95 % CI)

OR (95 % CI)

+

High (64)

2.04 (1.55 to 2.69)

2.10 (1.13 to 3.90)

p <0.01

p = 0.019

Driban 2013 [72]

Knee baseline BML volume (C)

48-month change in OARSI JSN grade (L)

Age, sex, BMI

NR

Baseline BML volume

+

High (61)

OR 1.27, 95 % CI 1.11 to 1.46

BML volume 48 month change (L) (TFJ)

(TFJ)

BML volume regression

OR 3.36, 95 % CI 1.55 to 7.28

Davies-Tuck 2010 [67]

Incident BML (new BML after 2 years with no BMLs at baseline) MRI TFJ (L)

Progression in semi-quantitative MRI cartilage defects score after 2 years. TFJ (L)

Age, gender, BMI, baseline cartilage volume

OR (95 % CI)

OR (95 % CI)

+

High (61)

Medial TFJ

Medial TFJ

Association in the lateral TFJ and a trend in the medial TFJ

1.86 (0.70 to 4.93) p = 0.21

2.63 (0.93 to 7.44) p = 0.07

Lateral TFJ

Lateral TFJ

3.0 (1.01 to 8.93) p = 0.05

3.13 (1.01 to 9.68) p = 0.05

Hochberg 2014 [44]

Semi-quantitative MRI baseline femoral condyle BML size (C)

Incident TKR over 6 years (L)

Age, gender, BMI, race, marital status, depressive symptoms, quality of life, mechanical pain, KL grade, clinical effusion.

Medial TFJ

Medial TFJ

+

High (61)

p <0.0001

p = 0.02

Raynauld 2011 [75]

Baseline semi-quantitative BML score (C) TFJ

Incidence of TKR over 3 years (L)

Age, sex, BMI, JSW, WOMAC,

NR

OR (95% CI)

+

High (61)

BML medial plateau

1.81 (1.08 to 2.03)

p = 0.025

Raynauld 2013 [74]

Baseline semi-quantitative BML WORMS score (C) medial TFJ

Incident TKR (L) 4 year follow up

Age, BMI, gender WOMAC, CRP

NR

TKR incidence

+

High (61)

OR (95 % CI) 2.107 (1.26 to 3.54) p = 0.005 time to TKR incidence hazard ratio (95% CI) 2.13 (1.38 to 3.30) p = 0.001

Time to TKR (L)

Crema 2014 [71]

MRI BML (semi-quantitative)

Cartilage loss (semi-quantitative)

Age, gender, BMI

NR

β = 0.37 to 0.64 p <0.001

+

High (56)

(C) all regions

(L) (all regions)

Guermazi 2014 Abstract [73]

Baseline semi-quantitative BML score WORMS (C)

Cartilage thickness loss over 30 months (L)

Age, sex, body mass index, and anatomical alignment axis (degrees)

NR

Combined BML score in the medial and lateral TFJ compartment

+

High (56)

OR 1.9, 95 % CI 1.1 to 3.3

Scher 2008 [87]

Presence of any baseline semi-quantitative MRI BMLs (C)

Incident TKR (L) over 3 years

Age

NR

OR (95 % CI)

+

High (56)

8.95 (1.49 to 53.68)

p = 0.02

Sowers 2011 [28]

Semi-quantitative MRI BML, size in TFJ (C)

Progression in KL grade

Nil

R (95 % CI) medial tibia ~ 0.46 (0.35 to 0.55)

NR

+

Low (53)

(11-year follow up) (L)

Lateral tibia ~0.23 (0.13 to 0.33)

Kothari 2010 [82]

Semi-quantitative baseline MRI BML, (WORMS) (C) TFJ

Semi-quantitative cartilage defect score change over 2 years (WORMS) (L) TFJ.

Age, sex, BMI, other bone lesions

OR 4.04,

OR 3.75,

+

Low (50)

95 % CI 2.25 to 7.26

95 % CI 1.59 to 8.82

Raynauld 2008 [85]

Change in BML size (mm) at 24 months in medial TFJ (L)

Medial cartilage volume (L) at 24 months in medial TFJ

Age, gender, BMI, meniscal extrusion and tear, pain and bone lesions at baseline

NR

Change in BML size with femoral cartilage volume loss

-

Low (50)

Larger medial BML size means more cartilage loss in medial compartment

β = −0.31

standard error (0.08)

p = 0.0004

Roemer 2009 [90]

Change in MRI semi-quantitative BML size (WORMS) (L) TFJ and PFJ

Progression in semi-quantitative cartilage defects in (WORMS) over 30 months (L) TFJ and PFJ

Age, sex, BMI, baseline KL grade

NR

OR (95 % CI)

+

Low (50)

Incident BML OR 3.5 (2.1 to 5.9)

Progression of BML 2.8 (1.5 to 3.2)

Resolution of BML OR 0.9 (0.5 to 1.6)

Stable BML OR 1.0 (reference)

Dore 2010 [76]

Baseline semi-quantitative BML severity (C) (medial and lateral TFJ)

Ipsi-compartmental annual Cartilage volume loss (L)

Age, sex, BMI, meniscal damage

NR

Baseline

-

Low (50)

BML severity

Bigger BML means bigger volume loss

β = −22.1 to −42.0, for all regions

(p <0.05)

Parsons 2014 Abstract [83]

Baseline semi-quantitative BML score (C)

Annual TFJ JSN (L)

Age, sex, baseline KL grade

NR

β = −0.10, 95 % CI

+

Low (50)

−0.18 to

−0.02

Wildi 2010 [95]

24-month regional change in TFJ BML score WORMS (L)

24-month regional change in cartilage volume (L)

nil

R correlation coefficients all <0.07

NR

NC

Low (50)

p >0.367 for all three compartments at 24 months

Pelletier 2007 [84]

Regional Semi-quantitative baseline BML score (medial or lateral TFJ) (C)

Regional cartilage volume over 24 months (medial or lateral TFJ) (L)

NR

Lateral compartment BML score

NR

Low (50)

β = −0.31, p = 0.001

Driban 2011 [79]

Baseline BML volume (C) and 24 month change in BML volume (L) in TFJ compartments

24-month change in full thickness cartilage lesion area (L)

Age, sex, body mass index

NR

Baseline BML volume r = 0.48, 95 % CI 0.20 to 0.69

+

Low (50)

Baseline femur BML volume with loss in ipsicompartmental full thickness cartilage lesion area.

p <0.002

Tanamas 2010 [89]

Baseline semi-quantitative MRI BML size (C) TFJ

Cartilage volume change over 2 years (L) TFJ Incident TKR over 4 years

Age, sex, BMI, baseline tibial cartilage volume and bone area

R (95 % CI)

R (95 % CI)

+

Low (50)

Total cartilage loss

Total cartilage loss

0.61 (−0.11 to 1.33)

1.09 (0.24, 1.93)

OR (95 % CI)

OR (95 % CI)

Incident TKR

Incident TKR

1.55 (1.04 to 2.29)

1.57 (1.04 to 2.35)

p = 0.03

p = 0.03

Madan-Sharma 2008 [93]

Baseline MRI semi-quantitative BML (C) TFJ

OARSI medial TFJ JSN grade progression over 2 years (L) TFJ

Age, sex, BMI, family effect

NR

0.9 RR,

NA

Low (47)

95 % CI 0.18 to 3.0

Tanamas 2010 [88]

Semi-quantitative change in MRI BML severity (C)

Incident TKR over 4 years (L)

Age, gender, KL grade

OR (95 % CI)

OR (95 % CI)

+

Low (47)

Medial TFJ

Medial TFJ

Association in the medial TFJ but not in the lateral TFJ

1.72

1.99

(0.93 to 3.18)

(1.01 to 3.90)

p = 0.08

p = 0.05

Lateral TFJ

Lateral TFJ

0.95 (0.48 to 1.88)

0.96 (0.48 to 1.94)

p = 0.89

p = 0.91

Roemer 2012 [86]

Semi-quantitative BML (WORMS) TFJ and PFJ (C)

Semi-quantitative cartilage score 6-month progression TFJ and PFJ (L)

Age, sex, treatment, and BMI.

NR

BML TFJ OR 4.74, 95 % CI 1.14 to 19.5

+

Low (44)

p = 0.032

BMLs and cartilage score correlate

BML PFJ OR, 1.63 (0.67 to 3.92)

Crema 2013 [78]

MRI incident BML (WORMS)

Progressive (30 month) semi-quantitative cartilage defect (WORMS) TFJ (L)

Age, sex, BMI, malalignment, meniscal disease

NR

OR (95 % CI)

+

Low (44)

TFJ

Medial TFJ 7.6

(L)

(5.1 to 11.3)

Lateral TFJ

11.9 (6.2 to 23.0)

Hernandez-Molina 2008 [81]

Crude presence of central BMLs on MRI (C) TFJ

Semi-quantitative cartilage defect (WORMS) (L) TFJ

Alignment, BMI, KL grade, sex, and age.

NR

Medial TFJ cartilage loss

+

Low (44)

OR 6.1,

95 % CI 1.0, 35.2

Koster 2011 [25]

Baseline BML presence (C) TFJ

Any progression in KL grade over 1 year (L) TFJ

Age, BMI

OR (95 % CI)

OR (95 % CI)

+

Low (44)

6.01 (1.92 to 18.8)

5.29 (1.64 to 17.1)

p = 0.002

p = 0.005

Hunter 2006 [91]

Change in MRI semi-quantitative BML score (L) TFJ

Change in semi-quantitative cartilage defect score (WORMS) (L) medial or lateral TFJ

Limb alignment

Ipsilateral cartilage loss

Ipsilateral cartilage loss

NA after adjustment

Low (44)

β = 0.65

β = 0.26

p = 0.003

p = 0.16

Contralateral cartilage loss

Contralateral cartilage loss

β = −0.27

β = −0.16

p = 0.22

p = 0.52

Roemer 2009 [94]

Baseline MRI BML crude presence or absence (WORMS) (L) TFJ

Semi-quantitative cartilage defect progression over 30 months (WORMS) (L) TFJ

Age, sex, race, BMI, alignment

OR (95 % CI)

OR (95 % CI)

NA

Low (44)

Slow cartilage loss OR 1.74 (0.85 to 3.55)

Slow cartilage loss OR 1.79 (0.83 to 3.87)

Fast cartilage loss OR 1.32 (0.37 to 4.78)

Fast cartilage loss OR 1.0 (0.24 to 4.10)

Kubota 2010 [92]

MRI BML semi-quantitative volume score change over 6 months (L) TFJ

KL grade progression over 6 months (L) TFJ

Nil

BML score higher in KL progression group

NR

NC

Low (39)

p = 0.044

Driban 2012 abstract [80]

MRI BML volume change (L) TFJ over 24 months

Change in cartilage thickness and denuded area of bone (L) TFJ over 24 months

Nil

Cartilage thickness

NR

+

Low (28)

r = −0.34, p = 0.04

denuded bone

r = 0.42, p = 0.01

Femoral cartilage indices p >0.05

Carrino 2006 [77]

Crude presence of MRI BML, TFJ (C) and (L)

Any grade of cartilage defect TFJ (C) and (L)

Nil

NR

NR

+

Low (22)

Baranyay 2007 [63]

MRI BML defined as large or not large/absent in the medial and lateral compartments of TFJ (C)

MRI semi-quantitative cartilage defects of medial and lateral compartments of TFJ (C)

Age, gender, BMI, cartilage volume or bone area

OR (95 % CI)

OR (95 % CI)

+

High (71 %)

Quantitative cartilage volume medial and lateral TFJ (C)

Cartilage defect Medial TFJ

Cartilage defect Medial TFJ

Cartilage defects

1.81 (1.26 to 2.59) p = 0.005

1.80 (1.21 to 2.69) p = 0.004

NA

Lateral TFJ

Lateral TFJ

Cartilage volume

1.52 (1.14 to 2.04)

1.45 (1.02 to 2.07)

p = 0.005

p = 0.04

No association with ipsicompartmental cartilage volume

No association with ipsicompartmental cartilage volume

Guymer 2007 [35]

Presence or absence of MRI BMLs

Presence or absence of semi-quantitative cartilage defects

Age, height, weight, and tibial cartilage volume

OR (95 % CI)

OR (95 % CI)

+

High (71)

(C) TFJ

(C) TFJ

Medial TFJ

Medial TFJ

A positive association is observed in the medial but not the lateral TFJ

6.46 (1.04 to 38.39)

3.51 (1.08 to 11.42)

p = 0.04

p = 0.04

Lateral TFJ

Lateral TFJ

1.17 (0.22 to 6.26)

1.02 (0.17 to 6.12)

p = 0.85

p = 0.98

Stehling 2010 [65]

Presence of any MRI semi-quantitative BMLs (C)

Presence of any WORMS MRI cartilage defects (C)

Age, gender and BMI, KL score, knee injury or knee surgery, family history of TKR and Heberden's nodes

NR

p <0.0001

+

High (71)

Torres 2006 [103]

MRI BML (WORMS) (C) TFJ and PFJ

Semi-quantitative cartilage (WORMS) (C)

Nil

R = 0.56

NR

+

High (68)

Ip 2011 [99]

Semi-quantitative MRI BML (C)

KL grade (C)

Age, sex, BMI, OA stage, joint effusion, and meniscal damage

NR

Highest BML score p <0.001

+

High (68)

Hayes 2005 [22]

Semi-quantitative MRI BML (C)

KL grade (C)

Nil

p = 0.005

NR

+

High (61)

Kornaat 2005 [100]

Semi-quantitative MRI BML (KOSS)

Semi-quantitative cartilage defects (KOSS) TFJ and PFJ (C)

Nil

OR (95 % CI)

NR

+

Low (57)

PFJ

TFJ and PFJ (C)

17 (3.8 to 72)

TFJ

120 (6.5 to 2,221)

Gudbergsen 2013 [98]

Semi-quantitative MRI BML (BLOKS) (C)

KL grade (C)

Nil

KL grade

NR

+

Low (57)

p = 0.046 lateral

p <0.001 medial

Link 2003 [101]

Semi-quantitative MRI BML, (C)

KL grade (C)

Nil

p <0.05

NR

+

Low (54)

Sowers 2003 [29]

Semi-quantitative MRI BML (C)

Semi-quantitative cartilage defect (C)

Nil

p for trend

NR

+

Low (54)

p <0.0001

Felson 2001 [96]

Semi-quantitative MRI BMLs (C)

KL grade (C)

Nil

NR

NR

+

Low (54)

Lo 2005 [102]

Semi-quantitative MRI BML (WORMS ≥ 1) (C)

KL grade ≥ 2 (C)

Nil

NR

NR

+

Low (50)

Meredith 2009 [64]

Sum of semi-quantitative MRI

Sum of semi-quantitative MRI

Nil

p <0.0003

NR

+

Low (50)

BML scores in the TFJ and PFJ (C)

Cartilage defect scores in the TFJ and PFJ (C)

Fernandez-Madrid 1994 [97]

Crude presence of MRI BMLs (C)

KL grade (C)

Nil

p <0.001

NR

+

Low (46)

Scher 2008 [87]

Semi-quantitative MRI BML (C)

Semi-quantitative cartilage defect (modified Noyes) (C)

Nil

p = 0.012

NR

+

Low (43)

Ratzlaff 2014 [104]

Total tibial BML volume 12 and 24 months before TKR and interval change between 12 and 24 (C) and (L) TFJ

Incident TKR (L)

NB matched cases and controls

OR (95 % CI)

NR

+

High (65)

12 months (C)

True of TFJ but not PFJ

1.68 (1.33 to 2.13)

24 months (C)

1.35 (1.02 to 1.78)

12 to 24 months change (L)

1.23 (1.03 to 1.46)

Zhao 2010 [105]

Baseline crude presence of MRI BMLs at (C) TFJ

Overlying cartilage defect progression after 1 year (WORMS) (L) TFJ

Nil

Change in cartilage defect scores for areas with and without underlying BMLs

NR

+

Low (56)

p = 0.00003

Aitken 2013 Abstract [17]

Semi-quantitative BMLs tibia, femur and patella

Cartilage volume and defect score tibia and femur

Age, sex, BMI

NR

Tibial cartilage volume

-

Low (47)

β = −433 mm³ per unit increase in BML

p <0.01

Stahl 2011 [41]

Semi-quantitative MRI BML size (WORMS) (L) TFJ

Semi-quantitative cartilage defect size (L) TFJ

Nil

NR

p <0.165

NA

Low (47)

De-Lange 2014 abstract [106]

Semi-quantitative osteophyte (KOSS) (C)

Radiographic progression of JSN of TFJ (L)

Age, gender, BMI and baseline JSN

NR

OR (95 % CI)

+

High (61)

1.8 (1.1 to 3.1)

Higher OST score, the higher the JSN

Liu 2014 Abstract [45]

Baseline semi-quantitative osteophyte score (WORMS) (C) TFJ

Incident TKR at 6-months follow up (L)

Activity of daily living disability score

NR

RR (95 % CI) 3.01 (1.39 to 6.52)

+

Low (50)

Sowers 2011 [28]

Semi-quantitative MRI osteophyte size in TFJ (C)

Progression in KL grade (11-year follow up) (L)

Nil

R (95 % CI) medial tibia ~ 0.65 (0.59 to 0.71)

NR

+

Low (53)

Lateral tibia ~0.57 (0.49 to 0.63)

Stehling 2010 [65]

Presence of any MRI semi-quantitative osteophytes (C)

Presence of any WORMS MRI cartilage defects (C)

Age, gender and BMI, KL score, knee injury or knee surgery, family history of TKR and Heberden’s nodes

NR

p = 0.0037

+

High (71)

Torres 2006 [103]

MRI osteophyte, (WORMS) TFJ and PFJ (C)

Semi-quantitative cartilage (WORMS) TFJ and PFJ (C)

Nil

R = 0.73

NR

+

High (68)

Hayes 2005 [22]

Semi-quantitative MRI osteophyte (C)

KL grade (C)

Nil

p <0.001

NR

+

High (61)

Meredith 2009 [64]

Sum of semi-quantitative MRI

Sum of semi-quantitative MRI

Nil

p <0.0001

NR

+

Low (50)

Osteophyte scores in the TFJ and PFJ (C)

cartilage defect scores in the TFJ and PFJ (C)

McCauley 2001 [26]

MRI central osteophyte presence (C) TFJ

MRI cartilage lesion presence (C) TFJ

Nil

Crude association of 32 of 35 central osteophytes having adjacent cartilage lesions

NR

+

Low (29)

Crude, unadjusted

Roemer 2012 [108]

MRI osteophyte

Cartilage defect (WORMS) (C)

Age, sex, BMI, race, TFJ radiographic OA

OR 2378.1,

OR 108.8,

+

Low (57)

95 % CI 249.8 to 22643.4

95 % CI 14.2 to 834.9

(WORMS) (C)

p for trend <0.0001

Link 2003 [101]

Semi-quantitative MRI osteophytes (C)

KL grade (C)

Nil

p <0.01

NR

+

Low (54)

Fernandez-Madrid 1994 [97]

Crude presence of MRI osteophytes (C)

KL grade (C)

Nil

p <0.001

NR

+

Low (46)

Kothari 2010 [82]

Semi-quantitative baseline MRI attrition

Semi-quantitative cartilage defect score change over 2 years (WORMS) (L) TFJ.

Age, sex BMI, other bone lesions

OR 3.17,

OR 1.85,

NA

Low (50)

95 % CI 1.64 to 6.16

95 % CI 0.71 to 4.82

(WORMS) (C) TFJ

Torres 2006 [103]

MRI attrition (WORMS) TFJ and PFJ (C)

Semi-quantitative cartilage (WORMS) TFJ and PFJ (C)

Nil

R = 0.75

NR

+

High (68)

Reichenbach 2008 [110]

Semi-quantitative MRI bone attrition (WORMS) (C)

KL grade and semi-quantitative cartilage defects (WORMS) (C)

Nil

NR

NR

+

Low (43)

Crude correlation

Neogi 2009 [109]

Baseline semi-quantitative MRI bone attrition size (WORMS) (C) TFJ

Cartilage defects progression (WORMS) after 30 months TFJ

Age, sex, BMI

OR 5.5,

OR 3.0,

+

Low (59)

95 % CI 3.0 to 10.0

95 % CI 2.2 to 4.2

Cicuttini 2004 [111]

Baseline quantitative MRI tibial bone area (C)

TKR incidence (L) over 4 years

Age, sex, height, weight, BMI, WOMAC, ROA severity

NR

OR (95 % CI)

+

High (78)

1.2 (1.0 to 1.4)

p = 0.02

Ding 2008 [20]

Baseline MRI tibial bone area (C) TFJ

Progressive cartilage volume loss (L) TFJ

Age, sex, BMI, OA family history, muscle strength and ROA.

β (95 % CI)

β (95 % CI)

-

High (72)

Medial femoral cartilage

Medial femoral cartilage

β = 0.17 (0.04 to 0.29)

β = 0.35 (0.14 to 0.56)

Total femoral cartilage

Total femoral cartilage

β = 0.07

β = 0.13

(0.003 to 0.14)

(0.02 to 0.25)

Ding 2006 [18]

Baseline MRI tibial bone area (C) TFJ

Change in semi-quantitative MRI cartilage defect scores over 2.3 years (L) TFJ

Age, sex, BMI, radiographic OA \features

NA

OR (95%CI)

-

High (61)

Medial TFJ

1.24 (1.01 to 1.51)

p = 0.04

Lateral TFJ

2.07 (1.52 to 2.82)

p <0.001

Everhart 2014 [114]

Baseline TFJ subchondral surface ratio of medial and lateral TFJ compartments (C)

Radiographic progression of lateral or medial TFJ knee OA at 48 months (L)

Sex, race, age, BMI, tobacco use, activity level, knee coronal alignment, baseline symptoms, injury history, surgery history, KL grade, and JSW

Unadjusted medial SSR vs progression of medial JSN

Neither medial nor lateral SSR was associated lateral or medial ROA progression in adjusted analysis p <0.05.

NA

High (61)

OR 1.43, 95 % CI 1.15 to 1.77

p = 0.0015

Medial SSR vs progression of lateral JSN

OR 1.87, 95 % CI 1.44 to 2.42

p <0.001

Davies-Tuck 2008 [112]

Baseline MRI tibial bone plateau area (C) TFJ

Progressive semi-quantitative cartilage defect score (L) medial and lateral TFJ

Age, sex, BMI, baseline cartilage defect score, baseline cartilage volume and baseline tibial plateau area

Lateral TFJ

OR (95 % CI)

+

High (56)

OR (95 % CI) −0.01 (−0.06 to 0.03) p = 0.59

Lateral TFJ 0.06 (0.004 to 0.11) p = 0.03 Medial TFJ 0.07 (0.03 to 0.12) p = 0.002

Carnes 2012 [113]

MRI tibial bone area (C)

Semi-quantitative cartilage defect progression TFJ (L)

Age, sex, BMI, cartilage defects, BML

Lateral tibial bone area OR 1.11, 95 % CI 1.0 to 1.23

OR (95 % CI) bone area medial 1.12 (1.01 to 1.26) and lateral tibial (1.35 (1.12 to 1.63)

+

Low (50)

Dore 2010 [68]

Baseline tibial bone area MRI (C)

Increase or no increase in semi-quantitative MRI tibial cartilage defects over 2.7 years (L)

Age, sex, body mass index, baseline cartilage defects, and subchondral bone mineral density

NR

OR (95 % CI) medial tibia 1.6 (1.0 to 2.6) p = 0.04 lateral tibia 2.4 (1.4 to 4.0) p <0.01

+ Bone area size is associated with increasing cartilage defect scores

Low (50)

Hudelmaier 2013 [180] Abstract

Annual change in segmented MRI knee bone area (L)

Baseline KL grade (C)

Nil

Medial tibia p <0.05

NR

+ The higher the KL grade the larger the increase in bone area

Low (50)

Ding 2005 [19]

MRI quantitative tibial bone area (C)

Semi-quantitative MRI knee cartilage defect severity scores (C) TFJ

Age, sex, BMI, family history, cartilage volume

β (95 % CI) medial TFJ 0.06 (0.03 to 0.09) lateral TFJ 0.09 (0.05 to 0.13)

β (95 % CI) medial TFJ 0.11 (0.07 to 0.15) lateral TFJ 0.17 (0.11 to 0.22)

+ Association maintained for the whole TFJ and by compartment

High (64)

Kalichman 2007 [165]

MRI patellar length ratio, trochlea sulcus angle (C)

JSN grade (C)

Age, sex, BMI

NR

Trochlea sulcus angle p for trend, medial JSN p = 0.0162, lateral JSN p = 0.1206

NC

High (64)

Kalichman 2007 [115]

MRI patellar length ratio, trochlea sulcus angle (C)

Cartilage defect (WORMS) (C)

Age, sex, BMI

NR

Trochlea sulcus angle p for trend, medial cartilage loss p = 0.0016, lateral cartilage loss p = 0.0009

+

Low (57)

Stefanik 2012 [116]

MRI lateral trochlear inclination and trochlear angle (C)

Semi-quantitative cartilage defect (WORMS) (C)

Age, sex, BMI

NR

Lateral trochlear inclination OR 2, 95 % CI 1.9 to 3.7, p <0.0001, trochlear angle OR 2.0, 95 % CI 1.2 to 3.5, p <0.0001

+

Low (57)

Frobell 2010 [107]

MRI bone area - manual segmentation (C)

KL grade, OARSI JSN grade (C)

Age and BMI

Medial tibia JSN and KL p <0.0125

Medial tibia JSN and KL p <0.0125

+

Low (57)

Wang 2005 [66]

Annual % change in tibial bone area (L) 2 years follow up

Baseline JSN (C)

Age, sex, BMI, WOMAC score, SF-36 score, physical activity, radiographic OA features, baseline tibial plateau bone area.

β (95 % CI) medial tibia β = 0.35 (−1.10 to 1.80) p = 0.63, lateral tibia −0.87 (−2.35 to 0.61) p = 0.25

β (95 % CI) medial tibia 1.88 (0.43 to 3.33) p = 0.01 lateral tibia −0.42 (−2.31 to 1.48) p = 0.66

+ Association with medial tibia but not in the lateral tibia

Low (57)

Jones 2004 [23]

Tibial bone area (MRI) (C)

Radiographic JSN (C)

Age, sex, height, weight

β (95 % CI) medial tibia β = −0.03 (−0.11 to 0.06), lateral tibia −0.00 (−0.07 to 0.06)

β (95 % CI) medial tibia β = −0.00 (−0.04 to 0.06), lateral tibia +0.00 (−0.04 to 0.05)

NA

Low (50)

Eckstein 2010 [117]

MRI tibial bone area (segmented) (C)

OARSI JSN grade (C)

Nil

p <0.01

NR

+

Low (43)

Bowes 2013 [118]

Change in segmented MRI 3D bone area over 4 years (L)

KL grade defined ROA knee (C) and (L)

Nil

NR bone area increased significantly faster in ROA vs non-ROA p <0.0001

NR

+ Higher KL grades had greater increase in bone area,

High (71)

Neogi 2013 [120]

MRI 3D bone shape (tibia, femur and patella) (C)

Incident TFJ ROA KL grade ≥2 (L)

Age, sex, BMI

NR

OR 3, 95 % CI 1.8 to 5.0

+ Developing 3D OA knee shape is associated with increasing ROA knee

High (65)

Hunter 2013 abstract [119]

Change in MRI knee bone area over 24 months (L)

Incident TFJ ROA (KL grade ≥2) (L)

NR

NR

Hazard ratio (95 % CI) range from 1.17 (1.08 to 1.27) to 3.97 (2.38 to 6.63), all highly statistically significant

+ for all bone regions Enlarging bone area associated with increasing ROA knee

Low (59)

Wluka 2005 [121]

Change in MRI tibial bone area (L)

Baseline radiographic JSN (C)

Age, BMI, pain, physical activity

Medial tibial bone area R = 160, 95 % CI 120 to 201, p <0.001

Medial tibial bone area R = 145, 95 % CI 103 to 186, p <0.001

+

Low (47)

Kotharii 2010 [82]

Semi-quantitative baseline MRI bone cyst (WORMS) (C) TFJ

Semi-quantitative cartilage defect score change over 2 years (WORMS) (L) TFJ.

Age, sex BMI, other bone lesions

OR 1.66, 95 % CI 0.55 to 4.99

OR 0.47, 95 % CI 0.11 to 2.03

NA

Low (50)

Tanamas 2010 [88]

Semi-quantitative change in MRI bone cyst size (L)

Knee Cartilage volume loss over 2 years (L) TFJ

Nil

β (95 % CI) lateral tibial cartilage loss in cyst regression relative to stable and progressive cysts

NR

+

Low (47)

β = −11.81 (−16.64 to −6.98)

Madan-Sharma 2008 [93]

Baseline MRI semi-quantitative bone cyst (C) TFJ

OARSI medial TFJ JSN grade progression over 2 years (L) TFJ

Age, sex, BMI and family effect

NR

RR 1.6, 95 % CI 0.5 to 4.0

NA

Low (47)

Carrino 2006 [77]

Crude presence of MRI bone cyst TFJ (C) and (L)

Any grade of cartilage defect TFJ (C) and (L)

Nil

NR

NR

+

Low (22)

Stehling 2010 [65]

Presence of any MRI semi-quantitative cyst (C)

Presence of any WORMS MRI cartilage defects (C)

Age, gender and BMI, KL score, knee injury or knee surgery, family history of TKR and Heberden’s nodes

NR

p = 0.0131

+

High (71)

Torres 2006 [103]

MRI bone cyst (WORMS) TFJ and PFJ (C)

Semi-quantitative cartilage (WORMS) TFJ and PFJ (C)

Nil

R = 0.75

NC

High (68)

Hayes 2005 [22]

Semi-quantitative MRI bone cyst (C)

KL grade (C)

Nil

p = 0.02

NR

+

High (61)

Link 2003 [101]

Crude presence of MRI bone cyst (C)

KL grade (C)

Nil

p <0.01

NR

+

Low (54)

Crema 2010 [122]

MRI Bone cysts (WORMS) (C)

Cartilage defect (WORMS) (C)

Nil

NR

NR

+

Low (50)

Okazaki 2014 [40]

Number of CT bone cysts (medial femur and tibia) (C)

Knee KL grade (C)

Nil

p <0.05

Nil

+with KL grade in medial TFJ

Low (50)

Lo 2012 Abstract [53]

MRI BVF, trabecular number, thickness and spacing (C)

OARSI medial TFJ JSN progression between 24 and 48 months (L)

Nil

OR 2.4, 95 % CI 1.1 to 5.0, p = 0.02

NR

BVF, trabecular number and thickness are positively associated with JSN progression but negatively associated with trabecular spacing.

Low (50)

Driban 2011 [50] Abstract

MRI bone volume fraction, trabecular number, spacing & thickness of medial tibia (C)

The presence of any grade of radiographic medial & lateral JSN (C)

Nil

R = 0.09 to 1.77

NR

+ Medial JSN associated with higher BVF, trabecular number and thickness but lower spacing

High (71)

Driban 2011 [49]

MRI bone volume fraction (C)

Radiographic JSN (C)

Nil

NR

NR

+ Higher JSN score, lower JSW) were associated with higher BVF

High (64)

Lindsey 2004 [123]

MRI bone volume fraction trabecular and trabecular number (TFJ) (C)

Cartilage volume of tibia or femur in contralateral TFJ compartment (C)

Nil

Medial TFJ cartilage with lateral TFJ BVF and trabecular number. β = 0.29 to 0.36, p = 0.0020 to 0.02

NR

+ With contralateral BVF and trabecular number, but – with trabecular spacing

High (64)

Lo 2012 [54]

MRI bone volume fraction, trabecular thickness, number, spacing and DXA BMD of (proximal medial tibia) (C)

Radiographic medial JSN grade (C)

Nil

All p <0.0001

Nil

+ (BV/TV, thickness, number, BMD) (spacing)

High (64)

Chiba 2012 [34]

MRI bone volume fraction and trabecular thickness of the medial & lateral femur & tibia. (C)

Metric JSW (radiographic) of the medial and lateral TFJ (C)

Nil

Bone volume fraction −0.48 (p <0.001) trabecular thickness −0.51 (p <0.001)

NR

-

Low (57)

Dore 2010 [68]

Baseline proximal tibial BMD, DXA (C)

Increase or no increase in semi-quantitative MRI tibial cartilage defects over 2.7 years (L)

Age, sex, BMI, baseline cartilage defects and subchondral tibial bone area

NR

OR (95 % CI) medial tibia 1.6 (1.2 to 2.1) p <0.01 lateral tibia 1.2 (0.9, 1.6) p = 0.19

+ Association only observed in medial tibia

Low (50)

Lo 2012 Abstract [53]

DXA-measured medial:lateral periarticular BMD (paBMD) (C)

OARSI medial TFJ JSN progression (L)

Nil

OR 8.4, 95 % CI 2.8 to 25.0, p <0.0001

nil

+ JSN association with baseline M:L paBMD

Low (50)

Bruyere 2003 [42]

Subchondral tibial bone BMD (DXA) (C)

Minimum medial JSW TFJ after one year (L)

Age, sex, BMI, minimum JSW

NR

R = −0.43, p = 0.02

Negative correlation i.e., lower BMD gives bigger JSW or less JSN

Low (44)

Dore 2009 [52]

DXA tibial subchondral BMD (C)

Radiograph JSN grade and MRI cartilage defect and volume (C)

Age, sex BMI

NR

Medial tibial BMD vs JSN R = 0.11, p <0.01, defect R = 0.16, p <0.01, cartilage volume R = 0.12, p = 0.01

+ Higher the BMD the greater the JSN and cartilage defects,

High (71)

Lo 2006 [55]

DXA medial:lateral BMD ratio at the tibial plateau (C)

Radiographic JSN grade (medial and lateral TFJ) (C)

Age, sex, BMI

p <0.0001

NR

+ With medial JSN, − with lateral JSN

High (71)

Lo 2012 [54]

DXA BMD (proximal medial tibia) (C)

Radiographic medial JSN grade (C)

Nil

p <0.0001

NR

+

High (64)

Akamatsu 2014 [31] Abstract

BMD (DXA) (C) (medial tibia and femoral condyle)

Medial TFJ JSN (radiographic) (C)

Nil

Tibia R = 0.571, p <0.001 femur R = 0.550, p < 0.001

NR

+ Medial femoral and tibial condyle BMD correlated with medial JSN

Low (57)

Bennell 2008 [56]

Volumetric BMD in tibial subchondral trabecular bone (C)

KL grade (C)

Age, sex, BMI

NR

p <0.05

NC BMD falls in posterior tibial plateau as KL increases but anteriorly increase in BMD noted

Low (59)

Mazzuca 2004 [37]

Baseline late-phase subchondral bone scintigraphy (adjusted for healthy diaphysis uptake) of the medial tibia and whole knee (C)

Progression of minimum JSN of the medial TFJ from baseline to 30 months (L)

Age, BMI, KL grade (NB all women)

r = 0.22 to 0.30 (p <0.05)

r = 0 to 0.08 (p <0.05)

NA after adjustment for covariates

High (56)

Mazzuca 2005 [38]

Baseline late-phase subchondral bone scintigraphy (adjusted for healthy diaphysis uptake) of the medial tibia and whole knee (C)

Progression of minimum JSN of the medial TFJ from baseline to 30 months (L)

Baseline JSW, treatment group

NR

Coefficient 0.221, 95 % CI 0.003 to 0.439, p = 0.049

+ The greater the scintigraphic bone signal the greater the JSN

High (56)

Dieppe 1993 [58]

Baseline late and or early-phase subchondral bone scintigraphy signal (C)

Progression of JSN by ≥2 mm or knee operation incidence after 5 years (L)

Nil

p <0.005

NR

+

Low (50)

Kraus 2009 [59]

Ipsilateral late-phase bone scintigraphy, semi-quantitative retention scoring of TFJ (C)

Ipsilateral OARSI scale of JSN (C)

Age, gender, BMI, osteophyte OARSI score, knee alignment knee symptoms

Coefficient 0.47 to 0.48 (p <0.0001)

Coefficient 0.26 to 0.29 (p = 0.0005 to 0.001)

+

High (71)

McCrae 1992 [62]

Late-phase ‘extended bone uptake’ pattern bone scintigraphy, presence around the TFJ (C)

Radiographic JSN presence (C)

Nil

OR 47.3, 95% CI 6.4 to 352, p <0.01

NR

+

Low (50)

Haverkamp 2011 [36]

2D bone shape knee. 1. Femur and tibial width 2. Elevation of lateral tibial plateau (C)

1. Presence of diffuse cartilage defects semi-quantitative scoring (MRI). 2. Presence of ROA knee (KL ≥2) (C)

NB (this is a population of women only) ROA models adjusted for age, BMI; cartilage defect models adjusted for KL only

OR (95 % CI) bone width vs knee ROA 2.03 (1.55 to 2.66) p <0.001 bone width Presence of diffuse cartilage defects p <0.001

OR (95 % CI) knee ROA 1.94 (1.44 to 2.62) p <0.001

+ Wider bones and elevated tibial plateau were associated with the presence of ROA knee. Cartilage defects were only associated with bone width

Low (46)