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Table 2 Knee pain associations by feature and quality score

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

Author Feature (method) Knee pain outcome Adjustment for confounders Association (magnitude) crude Association (magnitude) adjusted Association Quality score (%)
MRI bone marrow lesion - cohort studies
Foong 2014 [21] Change in BML size (L) and incident BMLs (L) in all three knee compartments WOMAC Knee pain severity at 2-year and 10-year visits (L) Age, sex, BMI, leg strength, and the presence of ROA NR Incident or change in total BML size β = 1.53 (95 % CI 0.37 to 2.70. + High (67)
Medial tibial change in BML size β = 2.96 (95 % CI 0.59-5.34 Incidence of BML or increase in size associated with increase in pain in the medial tibia
Driban 2013 [72] Knee baseline BML volume (C), BML volume change (L) (TFJ) 48-month change in WOMAC pain (L) Age, sex, BMI NR β = 0.21 + High (61)
(standard error 0.07) Longitudinal (L) changes in BML correlated with (L) changes in pain severity
p = 0.004
Dore 2010 [124] MRI BML size (L) regional or whole TFJ over 2.7 years Change in WOMAC pain (L) over 2.7 years Age, sex, BMI, leg strength, quality of life, and baseline pain, function β (95 % CI) Total BML size change = 1.06 (0.10 to 2.03) β (95 % CI) total BML size change = 1.13 (0.28 to 1.98) + High (56)
Kornaat 2007 [173] Semi-quantitative MRI BML change over 2 years (L) TFJ Mean WOMAC pain over 2 years Age, sex and BMI NR β (95 % CI) = 2 (−8 to 11) NA High (56)
Moisio 2009 [125] Baseline MRI semi-quantitative BML score (C) TFJ and PFJ Incident frequent knee pain 2 years after baseline (L) Age, sex, BMI, BML score, % denuded bone NR OR (95 % CI) medial tibia and femur 1.41 (0.86 to 2.33), lateral tibia and femur 1.70 (1.07 to 2.69) + Lateral TFJ BML score associated with incident frequent knee pain High (56)
Sowers 2011 [28] Semi-quantitative MRI BML, size in TFJ (C) Increasing WOMAC pain (L) Nil Medial and lateral TFJ BMLs both p <0.005 NR + Low (53)
Zhang 2011 [126] Semi-quantitative change in MRI BML size (L) TFJ over 30 months Incidence of frequent knee pain, and categorical severity (L) over 30 months Synovitis and effusions OR (95 % CI) Severity of frequent knee pain OR 3.0 (1.5 to 6.0) OR (95 % CI) Incident frequent knee pain p for trend = 0.006. Severity of frequent knee pain OR 2.2 (1.0 to 4.7) p = 0.047 + Ipsilateral association Low (50)
Wildi 2010 [95] 24-month change in regional TFJ BML score WORMS (L) 24-month change in WOMAC pain (L) Nil R <0.15, p >0.067 for all compartments NR NA, all compartments had no correlation Low (50)
Tanamas 2010 [89] Baseline semi-quantitative MRI BML size (C) Annual change in WOMAC pain (L) Nil NR NR NA Low (50)
MRI bone marrow lesion - cross-sectional studies
Zhai 2006 [135] Semi-quantitative MRI BML (C) WOMAC pain >1 (C) Age, BMI, sex, knee strength, chondral defects NR OR 1.44, 95 % CI 1.04, 2.00 + High (79)
Sharma 2014 [133] Semi-quantitative BML score WORMS TFJ or PFJ (C) Prevalent frequent knee symptoms (C) Age, sex, body mass index (BMI), previous knee injury, and previous knee surgery NR BMLs in any compartment OR 1.96, 95 % CI 1.38 to 2.77 + BML association with prevalent knee symptoms High (71)
Kornaat 2006 [130] Semi-quantitative MRI BML (C) Chronic pain presence (C) Age, sex, and BMI NR OR 1.13, 95 % 0.41, 3.11, p = 0.76 NA High (71)
Lo 2009 [131] Semi-quantitative MRI BML (BLOKS) (C) WOMAC pain (C) Synovitis, effusion scores p for trend = 0.0009 p for trend = 0.006 + High (71)
Stefanik 2014 abstract [134] BML (WORMS) (C) (patellofemoral joint) Prevalent knee pain (any pain in last 30 days) and pain VAS (C) Adjusted for age, sex, BMI, depressive symptoms and TFJ BMLs NR Isolated BML of the lateral PFJ, OR (95 % CI) 1.4 (0.9 to 2.0); medial PFJ, OR (95 % CI) 1.1 (0.8 to 1.5). Isolated lateral PFJ BMLs OR 6.6 (1.7 to 11.5) NC High (71)
Ratzlaff 2013 [132] Total BML volume in the femur or tibia (C) Weight-bearing knee pain WOMAC subscale (C) Age, sex, BMI, race, and medial minimum joint space width NR Total BML volume femur p = 0.003, tibia p = 0.101 + Femoral NA Tibial High (71)
Ip 2011 [99] Semi-quantitative MRI BML (C) WOMAC pain (C) Age, sex, BMI, OA stage, joint effusion, and meniscal damage NR Total WOMAC pain NC High (68)
R = 0.05, 95 % CI −0.04 to 0.14. Stair climbing pain R = 0.09 (0.00 to 0.18)
Torres 2006 [103] MRI BML (WORMS) TFJ and PFJ (C) Pain VAS (C) Age, BMI Coefficient 5.00, 95 % CI 3.00 to 7.00 Coefficient 3.72, 95 % CI 1.76 to 5.68 + High (68)
Kim 2013 [129] Summary score and severity of MRI BML (WORMS) (C) WOMAC pain severity or presence of knee pain (C) Age, sex, BMI, radiographic OA NR BML summary score medial TFJ OR 2.33, 95 % CI 1.02 to 5.33, p <0.001 + Severity of BML is proportional to WOMAC in medial compartment after adjustment High (64)
Moisio 2009 [125] Baseline MRI semi-quantitative BML score (C) TFJ and PFJ Presence of baseline moderate to severe knee pain (C) Percent denuded bone, age, sex, BMI NR Bone marrow lesion score, OR 0.95, 95 % CI 0.63 to 1.44. Not significant in all compartments NA found on cross-sectional analysis High (64)
Ratzlaff 2014 [48] Abstract Median BML volume (PFJ, TFJ) (C) Stair-climbing knee pain WOMAC (C) Nil TFJ p = 0.01, patellofemoral p = 0.01, femur p = 0.02, tibia p = 0.03 NR + High (64)
Hayes 2005 [22] Semi-quantitative MRI BML (C) Chronic pain presence (C) Nil p = 0.001 NR + High (61)
Ai 2010 [127] Semi-quantitative MRI BML (C) Pain verbal rating scale (Likert) (C) Nil p = 0.33 NR NA Low (57)
Bilgici 2010 [128] MRI BML (WORMS) (C) WOMAC pain, pain VAS (C) Nil WOMAC r = 0.508, p <0.01 Pain VAS r = 0.488, p <0.01 NR + Low (57)
Sowers 2003 [29] Semi-quantitative MRI BML (C) Chronic pain presence (C) Nil OR 5.0, 95 % CI 2.4 to 10.5 NR + Low (54)
Link 2003 [101] Semi-quantitative MRI BML (C) WOMAC pain (C) Nil p >0.05 NR NA Low (54)
Felson 2001 [96] Semi-quantitative MRI BMLs (C) Chronic knee pain presence (C) Radiographic severity, age, sex, and effusion score p <0.001 OR 3.31, 95 % CI 1.54 to 7.41 + Low (54)
Fernandez-Madrid 1994 [97] Crude presence of MRI BMLs (C) Crude pain presence (C) Nil NR NR NA Low (46)
MRI bone marrow lesion - case−control studies
Javaid 2010 [140] Baseline semi-quantitative MRI BML size (WORMS) (C) TFJ and PFJ Incident frequent knee pain after 15 months (L) Age, sex, race, BMI NR Whole knee OR 2.8, 95 % CI 1.2 to 6.5 + High (76)
Felson 2007 [181] Semi-quantitative MRI BML size increase (WORMS) (L) TFJ and PFJ Incident frequent pain at 15 months (L) Age, sex, race, BMI, quadriceps strength, KL score, malalignment, baseline BML score OR 4.1, 95 % CI 2.1 to 8.1 OR 3.2, 95 % CI 1.5 to 6.8 + High (71)
Javaid 2012 [139] Baseline Semi-quantitative MRI BML, (WORMS) (C) TFJ and PFJ Presence of frequent knee pain (C) after 2 years Nil OR 1.70, 95 % CI 1.08 to NR + Low (59)
Zhao 2010 [105] Baseline crude presence of MRI BMLs at (C) TFJ Change in WOMAC Pain (L) Nil p = 0.60 NR NA Low (56)
Stahl 2011 [41] Semi-quantitative MRI BML size (WORMS) (L) TFJ Changes in WOMAC score (L) Nil NR Data not shown NA Low (47)
MRI osteophyte – cohort studies
Sowers 2011 [28] Semi-quantitative MRI osteophyte, size in TFJ (C) Increasing WOMAC pain (L) Nil Medial and lateral TFJ BMLs both p <0.001 NR + Low (53)
MRI osteophyte - cross-sectional studies
Kornaat 2006 [130] Semi-quantitative MRI osteophyte (C) Chronic pain presence (C) Age, sex, BMI NR Patellofemoral OR 2.25, 95 % CI 1.06 to 4.77 + High (71)
Sengupta 2006 [136] Semi-quantitative MRI osteophyte (WORMS) (C) Pain severity WOMAC, chronic pain (C) Age, sex, BMI NR OR 0.97, 95 % CI 0.86 to 1.10 NA High (71)
Torres 2006 [103] MRI osteophyte, (WORMS) TFJ and PFJ (C) Pain VAS (C) Nil Coefficient 1.18, 95 % CI 0.63 to 1.72 Coefficient 0.50, 95 % CI 0.07 to 0.94 NC High (68)
Hayes 2005 [22] Semi-quantitative MRI osteophyte (C) Chronic pain presence (C) Nil p <0.001 NR + High (61)
Ai 2010 [127] Semi-quantitative MRI osteophytes (C) Pain verbal rating scale (Likert) (C) Nil p = 0.166 NR NA Low (57)
Hayashi 2012 [137] Crude presence of MRI osteophytes (C) Presence of pain on WOMAC pain subscale (C) Nil OR 4.2 to 6.4, p = 0.001-0.011 NR + Low (57)
Link 2003 [101] Semi-quantitative MRI osteophytes (C) WOMAC pain (C) Nil p >0.05 NR NA Low (54)
Fernandez-Madrid 1994 [97] Crude presence of MRI osteophytes (C) Crude pain presence (C) Nil NR NR NA Low (46)
MRI osteophyte - case–control studies
Javaid 2010 [140] Baseline semi-quantitative MRI osteophyte, size (WORMS) (C) TFJ and PFJ Incident frequent knee pain after 15 months (L) Age, sex, race, BMI NR Whole knee severe osteophyte OR 4.7, 95 % CI 1.3 to 18 + High (76)
MRI bone attrition - cross-sectional studies
Hernandez-Molina 2008 [138] Semi-quantitative MRI bone attrition (WORMS) (C) Pain severity and nocturnal pain (WOMAC) (C) Age, sex, BMI, BMLs, effusions and KL grade OR (95 % CI) pain severity OR 1.6 (1.1 to 2.3), nocturnal pain OR 1.1 (0.5 to 2.1) OR (95 % CI) pain severity OR 0.9 (0.6 to 1.4), nocturnal pain OR 1.0 (0.5 to 2.1). NA High (71)
Torres 2006 [103] MRI attrition, (WORMS) TFJ and PFJ (C) Pain VAS (C) Nil Coefficient 3.33, 95 % CI 1.79 to 4.87 Coefficient 1.91, 95 % CI 0.68 to 3.13 + High (68)
MRI bone attrition - case−control studies
Javaid 2012 [139] Baseline semi-quantitative MRI attrition size (WORMS) (C) TFJ and PFJ Presence of frequent knee pain (C) after 2 years Nil OR 2.40, 95 % CI 1.51 to 3.83 NR + Low (59)
MRI bone shape/dimension - cohort studies
Everhart 2014 [114] Baseline TFJ subchondral surface ratio of medial and lateral TFJ compartments (C) Incident frequent knee pain 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 NR Medial SSR OR 0.48, 95 % CI 0.30 to 0.75, p = 0.0009. Lateral SSR OR 1.27, 95 % CI 0.86 to 1.88, p = 0.19 - larger MSSR gets less incident frequent knee pain High (61)
MRI bone shape/dimension - cross-sectional studies
Ochiai 2010 [47] MRI irregularity of femoral condyle contour (C) Knee pain VAS (C) Nil Irregularity of femoral condyle contour r = 0.472, p = 0.0021 NR + Low (50)
MRI bone cyst - cohort studies
Sowers 2011 [28] Semi-quantitative MRI bone cyst size in TFJ (C) Increasing WOMAC pain (L) Nil NR NR analysis described as not significant but data not shown NA Low (53)
MRI bone cyst - cross-sectional studies
Kornaat 2006 [130] Semi-quantitative MRI bone cyst(C) Chronic pain presence (C) Nil NR Patellofemoral OR 1.83, 95 % CI (0.80 to 4.16) NA High (71)
Torres 2006 [103] MRI bone cyst (WORMS) TFJ and PFJ (C) Pain VAS (C) Age, BMI Coefficient 2.50, 95 % CI −0.38 to 5.38 Coefficient 0.82, 95 % CI −0.50 to 2.14 NA High (68)
Hayes 2005 [22] Semi-quantitative MRI bone cyst (C) Chronic pain presence (C) Age, sex, and BMI p <0.001 NR + High (61)
Hayashi 2012 [137] Crude presence of MRI bone cysts (C) Presence of pain on WOMAC pain subscale (C) Nil OR 6.7 to 17.8, p = 0.004 to 0.03 NR + Low (57)
Link 2003 [101] Crude presence of MRI bone cyst (C) WOMAC pain (C) Nil p >0.05 NR NA Low (54)
MRI bone cyst - case control studies
Javaid 2010 [140] Baseline semi-quantitative MRI bone cyst size (WORMS) (C) TFJ and PFJ Incident frequent knee pain after 15 months (L) Nil NR NR p >0.1 NA High (76)
Javaid 2012 [139] Baseline semi-quantitative MRI bone cyst size (WORMS) (C) TFJ and PFJ Presence of frequent knee pain (C) after 2 years Nil OR 1.61, 95 % CI 1.03 to 2.52 NR + Low (59)
qCT bone mineral density - cross-sectional studies
Burnett 2012 [57] BMD of patellar lateral facet (qCT) (C) WOMAC – knee pain at rest (C) Nil Total lateral patella facet p = 0.04, inferior lateral facet p = 0.005 NR   Low (57)
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) Pain severity VAS (C) Models adjusted for Age, BMI NR Bone width p = 0.167, lateral tibia plateau elevation p = 0.002 + Lateral tibial plateau associated with pain severity, NA bone width with pain severity Low (46)
  1. Positive correlation reported between bone feature and outcome measure (+); negative correlation reported between bone feature and outcome measure (−). BMI body mass index, BML bone marrow lesion, C a feature or outcome described in cross-section, knee pain on most days for at least the last month (chronic pain) confidence interval (CI), KL Kellgren-Lawrence, L a feature or outcome described longitudinally, NA no association, NC no conclusion could be found for an association between bone feature and outcome measure, NR not reported, OA osteoarthritis, OAI Osteoarthritis Initiative, OR odds ratio, PFJ patellofemoral joint, ROA radiographic osteoarthritis, SSR subchondral surface ratio VAS visual analogue scale, WOMAC Western Ontario and McMaster Universities arthritis index, qCT quantitative computed tomography