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Table 1 Knee structural associations by feature and quality grade

From: A systematic review of the relationship between subchondral bone features, pain and structural pathology in peripheral joint osteoarthritis

Author Feature (method) Structural progression outcome Adjustment for confounders Association (magnitude) crude Association (magnitude) adjusted Association Quality (score %)
MRI bone marrow lesion - cohorts  
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)
MRI bone marrow lesion - cross-sectional studies  
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)
MRI bone marrow lesion - case control studies  
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)
MRI osteophyte - cohort studies  
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)
MRI osteophyte - cross-sectional studies  
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)
MRI bone attrition - cohort studies  
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
MRI bone attrition - cross-sectional studies  
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
MRI bone attrition - case control studies  
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
MRI bone Shape/dimension – cohort studies  
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)
MRI bone shape/dimension - cross-sectional studies  
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)
MRI bone shape/dimension - case–control studies  
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)
MRI bone cyst - cohort studies  
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)
MRI bone cyst -– cross-sectional studies  
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)
CT bone cyst – cross-sectional studies  
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)
MRI subchondral bone morphometry - cohort studies  
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)
MRI subchondral bone morphometry - cross-sectional studies  
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)
DXA BMD - cohort studies  
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)
DXA BMD - cross-sectional studies  
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)
Volumetric CT BMD - case control studies  
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)
Knee scintigraphic subchondral bone cohort studies  
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)
Knee scintigraphic subchondral bone cross-sectional studies  
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)
2D knee bone shape – cross-sectional studies  
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)
  1. Positive correlation reported between bone feature and outcome measure (+); negative correlation reported between bone feature and outcome measure (−). BMD bone mineral density, BMI body mass index, BML bone marrow lesion, BOKS Boston osteoarthritis of the knee study, BLOKS Boston–Leeds osteoarthritis knee score, BVF bone volume fraction, C a feature or outcome described in cross-section, CT computed tomography, DXA dual-energy x-ray absorptiometry, GARP Genetics, osteoarthritis and progression study, JSN joint space narrowing, JSW joint space width, KL Kellgren-Lawrence, KOSS knee osteoarthritis scoring system, L a feature or outcome described longitudinally, MAK-2 mechanical factors in arthritis of the knee 2. NC no conclusion could be found for an association between bone feature and outcome measure, SWAN Michigan study of women’s health across the nation, MOST multicentre osteoarthritis study, MRI magnetic resonance imaging, NA no association. NR not reported, OA osteoarthritis, OAI Osteoarthritis Initiative, OR odds ratio, RR relative risk ratio, SSR subchondral surface ratio TASOAC Tasmanian older adult cohort, TFJ tibiofemoral joint, VAS visual analogue scale, WOMAC Western Ontario and McMaster Universities arthritis index, WORMS whole-organ magnetic resonance imaging score, CRP C-reactive protein, TKR total knee replacement, OARSI Osteoarthritis Research Society International, PFJ patellofemoral joint, ROA radiographic osteoarthritis