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Osteoarthritis Cartilage. Author manuscript; available in PMC 2011 January 1.
Published in final edited form as:
PMCID: PMC2818146

Subchondral bone marrow lesions are highly associated with, and predict subchondral bone attrition longitudinally: the MOST study

Frank W. Roemer, M.D.,* Tuhina Neogi, M.D., Ph.D.,§ Michael C. Nevitt, Ph.D., David T. Felson, M.D., M.P.H.,§ Yanyan Zhu, Ph.D.,§ Yuqing Zhang, M.Sc.,§ John A. Lynch, Ph.D., M. Kassim Javaid, M.D.,** Michel D. Crema, M.D., James Torner, Ph.D.,†† Cora E. Lewis, M.D.,‡‡ and Ali Guermazi, M.D.



Subchondral bone attrition (SBA) is defined as flattening or depression of the osseous articular surface. The causes of attrition are unknown, but remodeling processes due to chronic overload that are reflected as bone marrow edema-like lesions (BMLs) on MRI might predispose the subchondral bone to subsequent attrition. The aim of this study was to evaluate the cross-sectional and longitudinal association of BMLs with SBA in the same subregion of the knee.


The Multicenter Osteoarthritis (MOST) Study is a longitudinal observational study of individuals who have or are at high risk for knee osteoarthritis. Subjects with available baseline and 30-months follow-up MRI were included. Patients with a recent history of trauma or findings suggestive of post-traumatic bone marrow changes were excluded. Subchondral BMLs and SBA were scored semiquantitatively from 0 to 3 in 10 tibiofemoral subregions. We evaluated the association of prevalent BMLs at baseline with the presence of prevalent and incident SBA on a per-subregion basis using logistic regression. We also cross-sectionally evaluated the association of BML grade severity and presence of baseline SBA.


1025 knees were included. 8.9% of the analyzed knee subregions showed SBA present at baseline and 9.2% of subregions exhibited prevalent subchondral BMLs. The adjusted odds ratio (OR) for prevalent SBA for subregions with prevalent BMLs was 18.8 [95% confidence intervals 15.9–22.4]. A larger BML size was directly associated with an increased risk of prevalent SBA. 195 (2.2%) subregions exhibited incident SBA at follow-up. The adjusted OR for incident SBA was 5.3 [95% confidence intervals 3.6–7.7] when compared to subregions without BMLs as the reference.


Prevalent and incident SBA is strongly associated with subchondral BMLs in the same subregion. One explanation for the presence and development of SBA is subchondral remodeling due to increased stress, which is reflected as BMLs on MRI.

Keywords: Attrition, Magnetic Resonance Imaging, Osteoarthritis, Knee, Bone, Bone Marrow Lesions


Osteoarthritis (OA) is the most prevalent joint disease and is increasingly common in the aging Western society 1,2. Although, traditionally considered to be a disease of the hyaline articular cartilage, OA is a process of the whole joint including cartilage, bone and intra- and periarticular structures 37. Of these joint tissues, the subchondral bone probably plays an important role for the development and progression of OA 811. Increased subchondral bone turnover as measured by scintigraphy has been observed far in advance of any radiographic changes of OA and predicted subsequent radiographic changes of OA 12. Also a number of animal studies have shown that damage to the subchondral bone through loading may lead to cartilage damage 1315. Other experimental animal models demonstrate subchondral bone changes very early after induction of disease 16,17. Subchondral bone attrition (SBA) is defined on radiographs or magnetic resonance imaging (MRI) as flattening or depression of the articular surface unrelated to gross fracture 18,19. On MRI, the assessment of bone attrition is usually performed using the Whole-Organ Magnetic Resonance Imaging Score (WORMS) 20. Flattening or depression of the articular surfaces is graded based on the subjective degree of deviation from the normal contour on multiple tomographic images. As in radiographs, reading these deviations on MRIs is not simple, which is the reason why Reichenbach et al. suggested to use a conservative definition of attrition in order to detect “true” attrition on MRI 19.

An association of radiographically and MRI-detected SBA with pain has been reported by different research groups 18,21,22. Recent MRI-based studies have shown that SBA is present also in a relevant number of knees with early and even pre-radiographic OA 19. Also presence of SBA predicts adjacent progressive cartilage loss longitudinally and is strongly associated with malalignment within the same compartment 23,24.

As it is unknown what causes SBA in OA, one explanation could be subchondral remodeling processes and microfractures due to chronic overload that are reflected as subchondral bone marrow edema-like lesions on MRI 3,4. A recent cross-sectional population-based study reported that in more than 70% of all knees, both maximal SBA score and maximal bone marrow lesion (BML) score coexisted in the same knee region 18.

The causes of these remodeling processes could be overlying cartilage defects or other features that might increase mechanical subchondral stress such as meniscal damage and malalignment 4,10,25. Histologically, despite exhibiting normal bone tissue, BMLs seem to consist of a mixture of tissues that reflect chronic as well as active remodeling processes 2628. The alteration of the osseous surface contour could be a result of these subchondral remodeling processes including necrosis, fibrosis and focal osseous collapse 26,28. As subchondral bone marrow lesions are a non-specific finding on MRI and represent a multitude of differential diagnoses such as traumatic bone contusions and fractures with or without disruption of the articular surface, osteonecrosis, inflammation, idiopathic BMLs, and others, in this study only typical OA-related BMLs were assessed defined according to the literature26,29.

Thus, the aim of our study was to investigate whether subchondral BMLs are associated with prevalent SBA and whether BMLs in the same subregion of the knee precede SBA in the same subregion longitudinally using two different definitions of MRI detected SBA as previously suggested 19.

Patients and Methods

Study Design and Subjects

Subjects were participants in The Multicenter Osteoarthritis (MOST) Study, a prospective epidemiological study of 3,026 persons aged 50 to 79 years with a goal of identifying risk factors for incident and progressive knee OA in a sample either with OA or at high risk of developing disease. Those considered at high risk included persons who were overweight or obese, those with knee pain, aching or stiffness on most of the last 30 days, a history of knee injury that made it difficult to walk for at least one week, or previous knee surgery.

Subjects were recruited from two U.S. communities, Birmingham, Alabama and Iowa City, Iowa through mass mailing of letters and study brochures, supplemented by media and community outreach campaigns. The study protocol was approved by the Institutional Review Boards at the University of Iowa, University of Alabama, Birmingham, University of California, San Francisco and Boston University Medical Campus.

Subjects were excluded from MOST if they screened positive for rheumatoid arthritis 30, had ankylosing spondylitis, psoriatic arthritis, Reiter’s syndrome, had renal insufficiency that required hemo- or peritoneal dialysis, a history of cancer (except for non-melanoma skin cancer), had or planned to have bilateral knee replacement surgery, were unable to walk without assistance, or were planning to move out of the area in the next three years.

In the present study we included all participants with available baseline and 30-months follow-up MRI. These knees had been selected for MRI assessment for one or more of three substudies of MOST that were defined in the original grant proposal : 1) a cohort study of risk factors for radiographic OA progression consisting of randomly selected knees with either patellofemoral or tibiofemoral OA; 2) a case-control study of risk factors for incident radiographic OA; and 3) a case-control study of risk factors for new onset of consistent frequent knee pain31. Altogether 1025 subjects were selected for MRI reading and were included in the present study.


At baseline, all subjects underwent weight-bearing posteroanterior (PA) fixed flexion knee radiographs using the protocol by Peterfy et al. and a plexiglass positioning frame (SynaFlexer™) 32. A musculoskeletal radiologist and a rheumatologist experienced in reading study films, both blinded to case/control status and clinical data, graded all PA x-rays according to the Kellgren-Lawrence (KL) scale. Radiographic tibiofemoral OA was considered present if KL grade ≥2. If readers disagreed on the presence of radiographic OA, the film readings were adjudicated by a panel of 3 readers.

MRI Acquisition

MRIs were obtained in both knees with a 1.0 T dedicated MR system (OrthOne™, ONI Medical Systems, Wilmington, MA) with a circumferential extremity coil using fat-suppressed (fs) fast spin-echo proton density-weighted (PDw) sequences in two planes, sagittal (TR=4800 ms, TE=35 ms, 3 mm slice thickness, 0 mm interslice gap, 32 slices, 288 × 192 matrix, 2 excitations (NEX), 140 × 140 mm field of view (FOV), echo train length (ETL)=8) and axial (TR=4680 ms, TE=13 ms, 3 mm slice thickness, 0 mm interslice gap, 20 slices, 288 × 192 matrix, 2 NEX, 140 × 140 mm FOV, ETL=8) and a short tau inversion-recovery (STIR) sequence in the coronal plane (TR=6650 ms, TE=15 ms, TI=100 ms, 3 mm slice thickness, 0 mm interslice gap, 28 slices, 256 × 192 matrix, 2 NEX, 140 mm2 FOV, ETL=8).

MRI Interpretation

Two musculoskeletal radiologists, with 6 and 8 years experience in standardized semiquantitative MR assessment of knee OA, blinded to radiographic OA grade, study hypotheses, and clinical data, read BMLs and SBA according to the WORMS method 20. Baseline and follow-up MRIs were read paired and with the chronological order known to the readers. BMLs and SBA were scored in each of the 5 subregions in the medial and lateral compartments, for a total of 10 subregions per knee. BML size was scored from 0–3 based on the extent of regional involvement (0=none; 1=<25% of the subregion, 2=25–50% of the subregion; 3=>50% of the subregion). BMLs were defined as ill-delineated areas of hyperintensity directly adjacent to the subchondral plate on the STIR and fs PDw images. Knees that showed typical radiologic signs of traumatic bone contusions, osteonecrosis, fracture or malignant bone infiltration were excluded from the analysis. However, of all analyzed MRIs only one knee showed a subacute tibial depression fracture at follow-up and was excluded. Bone attrition was scored from 0 to 3 based on the subjective degree of deviation from the normal contour: 0=normal, 1=mild, 2=moderate and 3=severe. The weighted kappa coefficients of inter-observer reliability (performed on 30 knees read by both readers) for the readings of BMLs (comparing 0–3 scores in each subregion) and SBA (also comparing 0–3 scores in each subregion) were 0.64 and 0.63 respectively.

Knees that showed typical radiologic signs of traumatic bone contusions, osteonecrosis, fracture or malignant bone infiltration were excluded from the analysis. However, of all analyzed MRIs only one knee showed a subacute tibial depression fracture at follow-up and was excluded.

Analytic Approach

We evaluated the association of prevalent BMLs (score>0) at baseline with the presence of prevalent and incident SBA (score>0) in the same subregion across knees using logistic regression adjusting for age, gender, BMI, ethnicity and radiographic OA. Subregions without SBA (SBA=0) at baseline that developed SBA (SBA>0) at the follow-up visit were defined as incident SBA. Subregions without subchondral BMLs at baseline were defined as the reference group for the analysis. The correlation among SBA in different subregions in the same knee was adjusted by generalized estimation equation model. Analyses were also performed to evaluate the association between different baseline BML grades and presence of SBA. In addition, we performed a sensitivity analysis by defining prevalent SBA as all subregions with SBA baseline scores of ≥2 and incident SBA as subregions with baseline SBA scores of 0 or 1, and ≥2 at the follow-up visit (“strict” SBA definition). All statistical calculations were performed using SAS® software (Version 9.1 for Windows; SAS Institute; Cary, NC).


One thousand and twenty-five participants were included (1 knee per subject). Their mean age (SD) was 63 years (8), with a mean BMI (SD) of 30.3 (5.1). Sixty-four per cent were female. The average interval from baseline to the follow-up visit was 939 days, with a range of 827 to 1622 days. Of the 1025 knees studied, 51% had tibiofemoral radiographic knee OA at baseline (KL grade ≥2). At baseline, 24.5% of knees were graded as K/L 2, 22.2% as K/L 3 and 4.5% as K/L 4. At the 30-months follow-up visit the proportion of K/L 1 knees had decreased by about half and the number of K/L 4 knees had more than doubled. 398 (38.8%) of the subjects complained about knee symptoms on most days in the past 30 days prior to the baseline visit. At the follow-up this number had slightly increased. Varus malalignment was present in 510 (50.4%) and valgus malalignment in 201 (19.9%) of the knees at the baseline visit. The detailed demographic data are presented in Table 1.

Table 1
Demographic characteristics

10247 subregions were assessable at the baseline visit. 909 (8.9%) knee subregions showed SBA present at baseline. Using the strict definition of SBA, 289 (2.8%) of subregions showed SBA at baseline and 945 (9.2%) of knee subregions exhibited prevalent subchondral BMLs with the majority of these (n=667 / 6.5%) being grade 1 lesions. Grade 2 BMLs were observed in 181 (1.8%) and grade 3 lesions in 97 (1.0%) of subregions. Of the subregions without SBA (SBA = 0) at baseline (n=8699), incident attrition was observed in 195 (2.2%) subregions. Of the 9267 subregions showing no attrition at baseline (SBA = 0 or 1) 108 (1.2%) exhibited incident attrition using the strict SBA definition (Table 2).

Table 2
Baseline bone marrow lesions and attrition status

A strong association between prevalent BMLs and presence of SBA in the same subregion was observed cross-sectionally (Table 3). The larger the BML was the higher was the association observed. The association was comparable for both SBA definitions. In the adjusted model, baseline presence of BMLs (grade >0) in a subregion was associated with a 5.3 times higher odds (95% confidence intervals 3.6–7.7, p<0.001) of developing SBA in the corresponding subregion across all knees over 30 months when compared to a subregion without any BML at baseline (Figure 1). When using a stricter definition for the development of “definite” SBA (grade ≥2) within a subregion and considering grades 0 and 1 as “no attrition”, the corresponding odds ratio was 10.4 (95% confidence intervals 7.0–15.6, p<0.001) (Figure 2). Larger size of baseline BMLs was associated with higher odds of incident SBA at follow-up using the “strict” incident SBA definition, but not for the first definition (Table 4 and Table 5). However, using that definition only 1 subregion with a grade 3 BML at baseline showed incident SBA at follow-up.

Figure 1Figure 1Figure 1
Incident subchondral bone attrition in the medial tibiofemoral compartment. A. Sagittal fs PDw MRI at baseline depicts bone marrow lesion in the central subregion of the medial tibial plateau (arrowhead). No attrition is observed. B. Sagittal fs PDw MRI ...
Figure 2Figure 2
Incident subchondral bone attrition in the lateral tibia. A. Sagittal fs PDw MRI at baseline shows subchondral bone marrow lesion in the central and posterior subregions of the lateral tibial plateau (arrowheads). B. Sagittal fs PDw MRI at 30-months follow-up ...
Table 3
Presence of bone marrow lesions and prevalent bone attrition in the same subregion
Table 4
Baseline bone marrow lesions and incident bone attrition (defined as any grade ≥1)
Table 5
Baseline bone marrow lesions and incident bone attrition (using “strict” definition: SBA defined as any grade ≥2)


In this study, we found that presence of MRI-detected subchondral BMLs was highly associated with subchondral bone attrition in the same subregion cross-sectionally. Further, prevalent BMLs predicted development of attrition in the same subregion across knees over 30 months. This association could be confirmed also for a stricter definition of SBA as concerns had been raised that SBA might easily be “over-read” on MRI 19.

These findings suggest that BMLs, which are a reflection of increased subchondral metabolism and remodeling 26, might lead in some cases to alterations in the subchondral osseous plate and eventually weakening and deformity of the osseous articular contour. BMLs are thought to be a reflection of compartment-specific load most probably due to malalignment 3,4. As malalignment leads to altered stress in a joint, subchondral bone remodeling with resultant attrition can occur at those areas of increased stress in response to loads and in response to local microfractures as a result of those loads 33. The MRI feature of a subchondral BML then may be regarded as an intermediate of increased stress in this subregion, which may lead to attrition in later stages. Radin et al. described in an animal model of OA based on repetitive impulsive loading an increase in subchondral bone formation and a decrease in porosity, which has been associated with relative stiffening of bone. Horizontal splitting and deep fibrillation of the overlying articular cartilage followed these early bone changes 14,15. These theories seem to be supported by recent work by Neogi et al. who showed that malalignment is associated with subchondral bone attrition in a compartment-specific manner, suggesting that subchondral bone attrition may be a reflection of local mechanical load experienced through the knee joint 24. The same group also demonstrated that baseline presence of SBA is strongly associated with adjacent cartilage loss over time occurring within the same subregion of a given knee. These results were consistent for both compartments of the knee, although the effects were of greater magnitude in specific subregions that experience greater loading 23. Thus the co-occurrence of SBA, malalignment, cartilage loss and presence of BMLs within the same subregions of a knee, particularly for subregions thought to experience greater loading, seems to suggest that abnormal mechanical loading may be the common cause of these pathologies.

Depending on the definition, we found prevalent SBA in about 9% of the knee subregions, and using the strict definition in about 3% of subregions. Subchondral BMLs were seen in about 9% of the subregions with most of these being small lesions, which is a comparable number to the data presented by Roemer et al. in a recent publication from the MOST study 8. In our study cohort incident attrition was observed in about 2% of subregions and in 1% if the strict definition was applied. Hernandez-Molina et al. reported a prevalence of bone attrition (MRI defined as grades ≥2) in 28% of the knees with pain and in 10% of knees without pain 18. A subregional analysis concerning SBA prevalence was not performed in that study. Reichenbach et al. reported data from the Framingham study, where SBA prevalence was strongly associated with disease severity. In that study, MRI-detected SBA was present in about 14% of the knees with KL grade 0 and 100% in knees with a KL grade of 4 19.

There was a strong association between prevalent BMLs and SBA that increased with BML size. One might argue that this association only reflects disease severity as BMLs and attrition are thought to be more prevalent in advanced stages of OA 4,19. However, the strong spatial association of subchondral BMLs and attrition directly adjacent to each other suggests otherwise.

There are potential limitations to the current study. First, reader bias for finding SBA whenever a BML is present, and vice versa, cannot be ruled out completely. This is a general limitation of studies that examine associations among radiological features on the same image, as readers cannot be blinded to the presence of other features as both features are depicted in the identical images and thus are seen simultaneously. Readers were unaware of the study hypothesis, which makes reading bias unlikely. Secondly, our study results are limited to the tibiofemoral joint only. There is no validated reading of bone attrition in the femoropatellar joint, and we therefore limited our investigations to the tibiofemoral joint. We did not correlate the MRI findings with X-ray readings concerning attrition but a moderate to strong correlation between MRIs and radiographs for bone attrition of the tibiofemoral joint has been shown previously 19. We did not look at BML status at follow-up as we used BMLs only as a baseline predictor for subsequent SBA. It has been shown previously that subchondral BMLs are a highly variable feature of OA with possible progression, regression and also resolution over the course of the disease 8. It would be interesting to analyze if BMLs that predicted attrition always progressed as shown in the examples in Figure 1 and Figure 2 or if there are subregions with regressing or resolving BMLs exhibiting incident SBA. However, such an analysis was not the focus of the present study. There were too few subregions with incident SBA defined as grade ≥1 to evaluate the dose response relationship across the full range of BML size at baseline.

We did not analyze if clinical findings are associated with the MRI changes of the subchondral bone. However, this was not focus of the present study and would have gone beyond the scope of our work. Several groups have previously shown that subchondral BMLs seem to play an important role in explaining pain and bone attrition seems also to be independently associated with knee symptoms 18,31,34. Additional studies are needed to further elucidate if incident attrition is independently associated with onset of knee symptoms.

Subchondral BMLs exhibit typical signal characteristics on MRI and are common but non-specific findings. BMLs may be observed in conjunction with trauma, chronic cartilage damage and OA, as an idiopathic entity or as a concomitant feature of other pathologies such as osteonecrosis, inflammation or tumor 3540. In this context especially post-traumatic marrow pathologies have to be mentioned as these are common and traumatic bone contusions or subchondral fractures may easily be misinterpreted as chronic or OA-related BMLs. Several studies have used similar terminology and have shown different clinical outcomes depending on the extent and nature of these traumatic alterations 4144. We excluded traumatic BMLs by participants’ history and whenever typical traumatic MRI findings we observed 29,4547. The latter was found in one knee, which was excluded from the analysis.

In summary, we demonstrated that presence of subchondral bone marrow lesions is highly associated with concomitant bone attrition in the same subregions across knees. Further, subchondral BMLs are a strong predictor of future development of attrition when compared to regions without baseline BMLs. These findings suggest that subchondral remodeling processes, which are reflected on MRI as BMLs, predispose that articular region to weakening of the subchondral osseous plate, which eventually will be detectable as a deformity or depression of the osseous articular contour. The common pathogenetic mechanism of both processes might be increased loading due to malalignment or damage to other protective joint structures such as the menisci or an intact articular chondral surface.


We would like to thank the participants and staff of the MOST study at the clinical sites in Birmingham, AL and Iowa City, IA and at the Coordinating Center at UCSF, San Francisco, CA.

The MOST Study is supported by NIH grants from the National Institute on Aging to Drs. Lewis (U01-AG-18947), Torner (U01-AG-18832), Nevitt (U01-AG-19069), and Felson (U01-AG-18820).


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