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Abstract

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. REFERENCES

Objective

Bone marrow lesions are believed to increase risk of knee osteoarthritis (OA) progression. Whether their effect is local and whether it can be explained by other types of bone lesions concomitantly present in the same subregion is unclear. We evaluated bone lesion frequency in subregions without cartilage lesions and cartilage lesion frequency in subregions without bone lesions, and investigated the within-subregion bone marrow lesion/subsequent cartilage loss relationship after adjusting for other types of bone lesions at baseline.

Methods

Individuals with knee OA had magnetic resonance imaging at baseline and 2 years later. Cartilage integrity and bone marrow lesions, cysts, and attrition were scored within tibiofemoral subregions. Logistic regression, with generalized estimating equations to account for correlation among multiple subregions within a knee, was used to estimate odds ratios (ORs) for cartilage loss associated with bone marrow lesions, adjusting for age, sex, body mass index, and bone attrition and cysts in the same subregion.

Results

Analyzing 1,953 subregions among 177 knees, 90% of subregions had no bone lesions at baseline. Only 0–3% of subregions without cartilage lesions had bone lesions in the same subregion; in contrast, 5–33% of subregions without bone lesions had cartilage lesions. Bone marrow lesions at baseline were associated with cartilage loss in the same subregion at 2 years, adjusting for other types of bone lesions at baseline (adjusted OR 3.74, 95% confidence interval 1.59–8.82).

Conclusion

In subjects with knee OA, bone marrow lesions were rare at early disease stages but predicted subregional cartilage loss after accounting for the presence of other types of bone lesions in the same subregion.


INTRODUCTION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. REFERENCES

Bone underlying the cartilage surface of joints increases the contact area under load and reduces stresses within the cartilage (1). There has been a longstanding interest in the role of subchondral bone in the development and progression of osteoarthritis (OA) (2). Subchondral bone undergoes several changes in the setting of knee OA, including remodeling of the bone–cartilage interface, endochondral and intramembranous ossification of fibrovascular tissue penetrating the cartilaginous surface ultimately producing cartilage thinning and bone exposure, and other pathology, including bone sclerosis, pseudocyst formation, and attrition. Because much of what is known has come from animal model, tissue model, or cadaver studies, it remains unclear whether damage and loss of articular cartilage precede, accompany, or follow the development of lesions in subchondral bone, and what role bone lesions play in disease progression. Magnetic resonance imaging (MRI) techniques cannot as of yet routinely provide insight into the material properties and functional capacity of subchondral bone, but do afford an opportunity within longitudinal studies to examine the role of certain bone lesions in vivo in the natural history of human knee OA.

The subchondral bone marrow lesion (a noncystic area of ill-defined hyperintensity in T2-weighted, proton-density–weighted, STIR, or intermediate-weighted images, and of hypointensity in T1-weighted MRI images [3]) has received attention as a potential risk factor for knee OA progression. In the Boston Osteoarthritis Knee Study, bone marrow lesions at baseline were associated with subsequent radiographic (4) and MRI-based (5) measures of knee OA progression. A relationship between bone marrow lesions and worse cartilage integrity has been demonstrated in cross-sectional analyses (6) and in recent studies focusing on concurrent change (5, 7, 8). Certain questions regarding bone marrow lesions remain unanswered. Does their initial appearance precede or follow local cartilage lesion development? Is the effect on cartilage local? Is the effect explained by other bone lesions (i.e., subchondral bone attrition and cysts) in the vicinity?

Niu et al introduced methodology to analyze the effect of a lesion on cartilage integrity locally, i.e., within the same articular surface subregion (9). Although 1 study examining concurrent change in bone marrow lesions and cartilage applied a within-subregion approach (8), other reports describing the relationship between baseline bone marrow lesions (i.e., present at the beginning of the study period) and subsequent cartilage loss used a more traditional, compartment-level approach (4, 5). Also, previous studies have not taken into account possible confounding from other types of bone pathology within the same subregion. A within-subregion approach provides an opportunity to explore the question of whether bone marrow lesions or cartilage lesions appear first, by examining the frequency of bone lesions in subregions free of cartilage lesions and of cartilage lesions in subregions free of bone lesions.

Our goals were, in knees of individuals with knee OA, to determine: 1) in tibiofemoral surface subregions without any cartilage lesion, the frequency of subchondral bone lesions (i.e., bone marrow lesions, cysts, and attrition); 2) in subregions without any bone lesion, the frequency of cartilage lesions; and 3) whether the presence of bone marrow lesions at baseline is associated with the worsening of cartilage integrity within the same tibiofemoral subregion over the next 2 years, after adjusting for bone attrition and bone cysts within the same subregion at baseline.

MATERIALS AND METHODS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. REFERENCES

Sample.

Study participants were the members of a cohort of a natural history study of knee OA, the Mechanical Factors in Arthritis of the Knee 2 (MAK-2) study. MAK-2 cohort participants were recruited from community sources, letters to members of the registry of the Buehler Center on Aging, Health, and Society at the Feinberg School of Medicine at Northwestern University, and via medical center referrals.

Inclusion criteria were definite tibiofemoral osteophyte presence (Kellgren/Lawrence [K/L] radiographic grade ≥2) in one or both knees, and Likert category of at least “a little difficulty” for ≥2 items in the Western Ontario and McMaster Universities Osteoarthritis Index physical function scale. Exclusion criteria were corticosteroid injection within the previous 3 months; history of avascular necrosis, rheumatoid or other inflammatory arthritis, periarticular fracture, Paget's disease, villonodular synovitis, joint infection, ochronosis, neuropathic arthropathy, acromegaly, hemochromatosis, gout, pseudogout, osteopetrosis, or meniscectomy; or exclusion criteria for MRI such as presence of a pacemaker, artificial heart valve, aneurysm clip or shunt, metallic stent, implanted device (e.g., pain control/nerve stimulator, defibrillator, insulin/drug pump, ear implant), or any metallic fragment in an eye.

Approval was obtained from the Office for the Protection of Research Subjects/Institutional Review Boards of Northwestern University and Evanston Northwestern Healthcare. Written consent was obtained from all participants.

MRI acquisition and reading.

All participants had MRI of both knees using a commercial knee coil and 1 of 2 whole-body scanners (1.5T in 162 participants or 3.0T in 15 participants; GE Healthcare, Waukesha, WI). Each participant was scanned and rescanned on the same machine with the same protocol at the 2 time points (baseline and 2-year followup). Sequences included axial and double oblique coronal T1-weighted 3-dimensional spoiled gradient-echo images with water excitation, coronal T1-weighted spin-echo, and sagittal fat-suppressed dual-echo turbo spin-echo. The acquisition parameters for 1.5T and 3.0T are reported in Table 1.

Table 1. Acquisition parameters*
SequenceTR, msecTE, msecFA, degreesFOV, cmMatrix size, pixelsSlice thickness/gap, mmAcquisition time, minutes:seconds
  • *

    TR = repetition time; TE = echo time; FA = flip angle; FOV = field of view; SE = spin-echo; TSE = turbo spin-echo; 3-D = 3-dimensional; SPGR = spoiled gradient-recalled acquisition.

1.5T       
 Coronal T1-weighted SE574119012256 × 2563.0/3.04:54
 Sagittal fat-suppressed dual-echo TSE3,80019/659014256 × 2563.0/3.07:06
 Axial and double oblique coronal T1-weighted 3-D SPGR images with water excitation17.27.851016512 × 5121.5/0.08:51
3.0T       
 Coronal T1-weighted SE800119012288 × 2243.0/0.56:08
 Sagittal fat-suppressed dual-echo TSE3,00016/659014224 × 2243.0/1.05:42
 Axial and double oblique coronal T1-weighted 3-D SPGR images with water excitation18.25.71516512 × 5121.5/0.09:00

Following a detailed reading protocol, each knee was scored using the Whole-Organ Magnetic Resonance Imaging Score (WORMS) method (10). Specifically, 3 subregions (anterior, central, and posterior) of the medial and lateral femoral condyles and the medial and lateral tibial plateaus were each scored separately for subchondral bone marrow lesions, bone cysts, bone attrition, and cartilage integrity. For each lesion, each subregion received its own score.

At each subregion, cartilage morphology was scored on a 7-point integer scale from 0 to 6, where 0 = normal thickness and signal; 1 = normal thickness but increased signal on T2-weighted images; 2 = solitary, focal, partial, or full-thickness defect ≤1 mm in width; 3 = multiple areas of partial-thickness loss or a grade 2 lesion >1 mm, with areas of preserved thickness; 4 = diffuse, >75%, partial-thickness loss; 5 = multiple areas of full-thickness loss, or a full-thickness lesion >1 mm, with areas of partial-thickness loss; and 6 = diffuse, >75%, full-thickness loss. Cartilage lesion presence was defined as a score ≥2.

Subchondral bone marrow lesions and bone cysts were each scored as integers from 0 to 3, where 0 = normal; 1 = mild, <25% of the region; 2 = moderate, 25–50% of the region; and 3 = severe, >50% of the region. Subchondral bone attrition (flattening and depression of the articular surfaces) was scored as 0, 1, 2, or 3, for normal, mild, moderate, or severe attrition, respectively. Bone marrow lesions, bone attrition, and bone cysts were considered present in a subregion if the corresponding score was greater than zero. MR images were read by 1 of 3 expert readers whose reliability with this scoring system has been published (10). The readers were blinded to the chronological order of the 2 acquisitions and to the hypotheses to be tested in this study.

Radiographic acquisition and reading.

The full protocol has been previously published (11). Briefly, all participants had bilateral, anteroposterior, weight-bearing knee radiographs at baseline in the semiflexed position with fluoroscopic confirmation of superimposition of the anterior and posterior tibial plateau lines and centering of the tibial spines within the femoral notch. To describe the knees, the K/L global radiographic score was used (0 = normal; 1 = possible osteophytes; 2 = definite osteophytes without definite joint space narrowing [JSN]; 3 = definite JSN, some sclerosis, and possible attrition; and 4 = large osteophytes, marked JSN, severe sclerosis, and definite attrition). Reliability for radiographic grading for the radiographic reader (LS) was high (κ = 0.86).

Statistical analysis.

Data from the dominant knee (defined as the knee with which the participant would kick a ball) of each participant were analyzed. Twelve subregions were included per knee, 3 each from the medial tibial, medial femoral, lateral tibial, and lateral femoral surfaces. Subregions with the worst cartilage integrity score (6, or diffuse full-thickness loss of cartilage) were excluded because further worsening was not possible. The relationship between bone marrow lesions (presence versus absence) at baseline and worsening of cartilage integrity (i.e., an increase in score by ≥1 point) between baseline and 2 years afterward within the same subregion was examined using logistic regression with generalized estimating equations to account for correlation among multiple subregions within one knee. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were derived for each model. SAS software, version 9.1 (SAS Institute, Cary, NC) was used. Analyses were adjusted for age, sex, and body mass index (BMI), and further adjusted for bone attrition and bone cysts within the same subregion at baseline.

RESULTS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. REFERENCES

Of the 202 participants who completed the baseline evaluation, 10% did not participate in the 2-year followup evaluation, evenly distributed between these reasons: deceased, bilateral total knee replacement, moving away, or new MRI contraindication. Of the remaining 182 dominant knees (from 182 participants), 5 knees were excluded for missing subregional data. The sample consisted of 177 knees from 177 participants with a mean ± SD age of 66.2 ± 11.5 years and a mean ± SD BMI of 30.3 ± 6.2 kg/m2. Of the 177 participants, 139 (79%) were women and 38 (21%) were men. The majority of knees (74%) were graded K/L 2 or K/L 3. Of the 2,124 subregions (177 knees, 12 subregions per knee), 171 subregions were excluded from all analyses for having advanced disease that could not progress further (i.e., a cartilage integrity score of 6, corresponding to diffuse, full-thickness loss of cartilage), leaving an analytic sample of 1,953 subregions from 177 subjects/knees.

In these 177 knees with 1,953 subregions, 82 knees (46%) had a bone marrow lesion in ≥1 subregion at risk for progression, 68 (38%) had bone attrition in ≥1 subregion, and 39 knees (22%) had a bone cyst in ≥1 subregion. Of the 1,953 regions, 1,750 subregions (90%) had no bone marrow lesions, bone attrition, or bone cysts. Bone marrow lesions occurred alone in 71 subregions, bone attrition alone in 51 subregions, and bone cysts alone in 15 subregions. Twenty-five subregions had both bone marrow lesions and bone attrition, 17 subregions had bone marrow lesions and bone cysts, and 3 subregions had bone cysts and bone attrition, whereas 21 subregions had all 3 bone lesions.

Next, we determined the frequency of subchondral bone lesions in subregions without cartilage lesions, and the frequency of cartilage lesions in subregions without bone lesions. Bone marrow lesions, bone attrition, and bone cysts were infrequently found (≤3% of the time) in subregions without cartilage lesions (Table 2). In subregions without any of these bone lesions, cartilage lesions were more frequent (found 5–33% of the time) (Table 3).

Table 2. Frequency of subchondral bone lesions in subregions without cartilage lesions at baseline
Compartment, surface, and subregionKnees without any cartilage lesions in the subregion, no.Subchondral bone lesions in the subregion, no. (%)
Bone marrow lesionBone attritionBone cyst
Medial    
 Femoral    
  Anterior1101 (1)1 (1)0 (0)
  Central981 (1)0 (0)0 (0)
  Posterior1343 (2)1 (1)1 (1)
 Tibial    
  Anterior1533 (2)0 (0)5 (3)
  Central1070 (0)2 (2)0 (0)
  Posterior1461 (1)0 (0)3 (2)
Lateral    
 Femoral    
  Anterior1103 (3)1 (1)2 (2)
  Central1260 (0)1 (1)0 (0)
  Posterior1461 (1)0 (0)1 (1)
 Tibial    
  Anterior1572 (1)0 (0)3 (2)
  Central1321 (1)0 (0)0 (0)
  Posterior1532 (1)0 (0)2 (1)
Table 3. Frequency of cartilage lesions in subregions without subchondral bone lesions (bone marrow lesion, bone attrition, or bone cysts) at baseline
Compartment, surface, and subregionKnees without any subchondral bone lesions in the subregion, no.Cartilage lesions in the subregion, no. (%)
Medial  
 Femoral  
  Anterior16153 (33)
  Central13538 (28)
  Posterior17342 (24)
 Tibial  
  Anterior16618 (11)
  Central13933 (24)
  Posterior17027 (16)
Lateral  
 Femoral  
  Anterior13528 (21)
  Central15631 (20)
  Posterior15512 (8)
 Tibial  
  Anterior16915 (9)
  Central14816 (11)
  Posterior1588 (5)

The percentages of participants with each subchondral bone lesion in ≥1 subregion at risk for cartilage loss (i.e., with a cartilage integrity score <6) are shown in Table 4. Among subjects with a bone lesion in ≥1 subregion at risk for further cartilage loss, the average number of subregions with these bone lesions was relatively small, i.e., 1.4–1.6 subregions. The percentage of participants with cartilage loss in ≥1 subregion with a bone lesion ranged from 15% for bone cysts to 24% for bone attrition among participants at risk for cartilage loss (Table 4).

Table 4. Person-specific extent of subregion involvement by bone lesion type and frequency of cartilage loss
LesionNo. (%) of persons with specified bone lesion in ≥1 subregion at risk for cartilage loss (n = 177 persons)Persons with bone lesion in ≥1 subregion at risk for cartilage loss
Average number of subregions/knee with specified lesion% of persons with cartilage loss in subregion with bone lesion
Bone marrow lesion82 (46)1.619/82 (23)
Subchondral bone attrition68 (38)1.516/68 (24)
Subchondral bone cyst39 (22)1.46/39 (15)

We estimated the OR for cartilage loss over a 2-year followup period (outcome variable) associated with the presence of bone marrow lesions within the same subregion. Cartilage loss was significantly associated with the presence of bone marrow lesions at baseline in the unadjusted model (OR 4.04, 95% CI 2.25–7.26) (Table 5). This relationship persisted after adjustment for age, sex, and BMI (adjusted OR 3.88, 95% CI 2.12–7.10), and after further adjustment for the presence of other types of bone lesions within the same subregion (adjusted OR 3.74, 95% CI 1.59–8.82). Bone attrition at baseline was significantly associated with cartilage loss in the same subregion after adjusting for age, sex, and BMI, but not after further adjustment for the other types of bone lesions (Table 5).

Table 5. Odds ratios for worsening of cartilage integrity between baseline and 2 years within the same subregion (n = 1,953 subregions from 177 knees of 177 subjects)*
Independent variableUnadjustedAdjusted for age, sex, and BMIAdjusted for age, sex, BMI, and other types of bone lesions within the same region
  • *

    Values are the odds ratio (95% confidence interval). BMI = body mass index.

Bone marrow lesion4.04 (2.25–7.26)3.88 (2.12–7.10)3.74 (1.59–8.82)
Subchondral bone cyst1.68 (0.56–5.00)1.66 (0.55–4.99)0.47 (0.11–2.03)
Subchondral bone attrition3.17 (1.64–6.16)2.95 (1.46–5.96)1.85 (0.71–4.82)

DISCUSSION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. REFERENCES

Our analyses show, in individuals with knee OA, that the presence of bone marrow lesions at baseline was associated with a nearly 4-fold increase in the likelihood of worsening of cartilage integrity in the same subregion over the next 2 years after adjusting for other types of bone lesions within the same subregion. Baseline data revealed that many knees had a bone marrow lesion in ≥1 subregion, but 90% of subregions had no bone marrow lesion, no bone attrition, and no bone cysts. When a bone marrow lesion was present in a knee, on average it was present in a relatively small number, i.e., less than 2 subregions. Bone lesions were rare in subregions without cartilage lesions; cartilage lesions were more common in subregions without bone lesions.

Previous reports from the Boston Osteoarthritis Knee Study that examined the relationship between the presence of bone marrow lesions at baseline and knee OA progression in a subsequent period revealed a relationship at a compartment level, i.e., presence of any bone marrow lesion in a compartment was associated with any worsening of radiographic scores (4) or cartilage integrity in that compartment (5), adjusting for age, sex, and BMI. We were able to demonstrate this relationship within the same articular surface subregion, and, further, that the bone marrow lesion/cartilage-worsening relationship was not explained by bone attrition or bone cysts that may have been present within the same subregion.

The analytic approach that we applied for the analyses of multiple subregions within a knee was similar to that used by Roemer et al (8). The utility of using subregional MRI data to examine focal lesion effects was highlighted by Niu et al (9), who conducted a matched case–control study using knees that had all subregions eligible for cartilage loss at baseline and had cartilage loss in ≥1 site at followup. The subregions with cartilage loss (cases) were matched to the sites without cartilage loss (controls) within each knee. They used conditional logistic regression, adjusting for the compartment.

A previous report of the subregional bone marrow lesion/cartilage-worsening relationship from the Multicenter Osteoarthritis (MOST) Study focused on whether bone marrow lesions and cartilage change together (8), an interesting but different question than we pose here. Roemer et al found that a persistent absence of bone marrow lesions over time was associated with a decreased risk of concurrent cartilage loss, whereas worsening and new bone marrow lesions were associated with a high risk of concurrent cartilage loss, adjusting for age, sex, BMI, and K/L grade (8). In the Boston Osteoarthritis Knee Study, Hunter et al found that an increase in bone marrow lesions was associated with a concurrent worsening of cartilage score at the compartment level (5). Raynauld et al found a relationship between concurrent cartilage volume loss and change in size of bone marrow lesions in the medial condyle and the medial tibial plateau (7). These studies consistently found that bone marrow lesions and cartilage get worse together.

Recent reports imply a need to consider other types of bone lesions in the analysis of the bone marrow lesion/cartilage loss relationship. In the MOST Study, bone marrow lesions were associated with prevalent and incident bone attrition in the same subregion, adjusting for age, sex, BMI, and ethnicity (12). Also, in other analyses from the MOST Study, bone attrition was associated with cartilage loss in the same subregion (13), and bone marrow lesions were associated with cysts in the same subregion (14). However, we were not able to find any reports of the bone marrow lesion/cartilage loss relationship in which analyses were adjusted for the presence of these other types of bone lesions.

We found no bone lesions in 90% of subregions. This is similar to results from the MOST Study, in which 92% of subregions had no bone marrow lesions at baseline (8), and 95% of subregions had no bone cysts (14). A bone marrow lesion was present in ≥1 subregion in 62% of knees in the MOST Study (8) and in 57% of knees in the Boston Osteoarthritis Knee Study (5). The lower number (46%) in our study may reflect the fact that we excluded subregions with the most severe stage of disease (a score of 6, or diffuse, full-thickness loss).

In an arthroscopic study, bone marrow lesions were present (per MRI reader blinded to arthroscopy findings) beneath 105 (19%) of 554 articular cartilage defects but only 1% of articular surfaces that appeared normal at the time of surgery (6). Higher grades of articular cartilage defects were associated with a higher prevalence and greater depth and cross-sectional area of bone marrow lesions (6). In our examination of the baseline data, we found that bone marrow lesions, attrition, and cysts were each very rare in subregions free of any cartilage lesion. In contrast, cartilage lesions were more common in subregions free of any of these bone lesions.

Together, these arthroscopic results and our results support the possibility that cartilage lesions typically develop before bone marrow lesions, and that bone marrow lesion development depends on the presence of preexisting cartilage damage. It is possible that bone marrow lesions have a deleterious effect on osteoarthritic disease that is already underway. However, it is important to acknowledge the alternative possibility, that bone marrow lesions are a local epiphenomenon of cartilage status with no impact on the rate of cartilage loss. This can be further explored in studies with more than 2 time points.

Our study has limitations. The WORMS method may be relatively insensitive in the detection of small changes. We used the cartilage integrity score from the WORMS because it enabled us to examine the relationship between bone marrow lesions and subsequent worsening of cartilage integrity within the same subregion. Despite the limitations of the WORMS method, we were able to detect this relationship. The relatively small number of men precluded analysis to confirm that the results were similar specifically for men.

It is important to emphasize that other aspects of subchondral bone structure and function may play a pivotal role in knee OA disease progression. The bone lesions that are the focus of our and other studies may not capture, except perhaps in an indirect way, key mechanical and material properties of subchondral bone, how it functions, how it handles load at the knee, and its ability to help articular cartilage. Methods to assess these subchondral bone parameters in vivo should be refined and applied in longitudinal studies.

In conclusion, in individuals with knee OA, subchondral bone lesions were rare in tibiofemoral subregions without cartilage lesions; cartilage lesions were more common in subregions without bone lesions. The presence of bone marrow lesions at baseline was associated with worsening of cartilage integrity in the same tibiofemoral subregion over the next 2 years in analyses adjusting for bone attrition and cysts in the same subregion.

AUTHOR CONTRIBUTIONS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. REFERENCES

All authors were involved in drafting the article or revising it critically for important intellectual content, and all authors approved the final version to be submitted for publication. Dr. Sharma had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study conception and design. Kothari, Dunlop, Cahue, Sharma.

Acquisition of data. Kothari, Guermazi, Marshall, Cahue, Prasad, Sharma.

Analysis and interpretation of data. Kothari, Guermazi, Chmiel, Dunlop, Song, Almagor, Sharma.

REFERENCES

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. REFERENCES
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    Crema MD, Roemer FW, Marra MD, Niu J, Zhu Y, Lynch J, et al. MRI-detected bone marrow edema-like lesions are strongly associated with subchondral cysts in patients with or at risk for knee osteoarthritis: the MOST Study [abstract]. Osteoarthritis Cartilage 2008; 16: S160.