Bone marrow edema and osteitis in rheumatoid arthritis: the imaging perspective
© BioMed Central Ltd 2012
Published: 28 September 2012
Magnetic resonance imaging bone marrow edema is an imaging feature that has been described in many conditions, including osteomyelitis, overuse syndromes, avascular necrosis, trauma, and inflammatory arthritides. In rheumatoid arthritis (RA), bone edema has special significance as it has been shown to be a common and widespread lesion that is often apparent at the hands and wrists but has also been described elsewhere, including the feet. It may occur in early or late disease and has been shown in several large cohort studies to have major negative implications for prognosis. It is the strongest predictor of erosive progression yet to be identified and characteristically occurs in those patients with the most aggressive and potentially disabling disease. In patients with undifferentiated arthritis, bone edema also predicts progression to criteria-positive RA, both independently and to a greater extent when combined with anti-cyclic citrullinated peptide status or rheumatoid factor positivity. Its histological correlate in the late stages of RA has been shown to be osteitis, in which the bone marrow beneath the joint is invaded by an inflammatory and vascular lymphoplasmacytic infiltrate. This lies adjacent to trabecular bone, where increased numbers of osteoclasts have been observed within resorption lacunae, suggesting a mechanistic link between inflammation and erosive bone damage. This could lead to erosion both of the overlying cortex, leading to classic radiographic rheumatoid erosions, and of local trabecular bone, possibly contributing to periarticular osteopenia and cyst formation. In addition to synovitis, osteitis is now regarded as a major rheumatoid lesion that is responsive to therapeutic intervention.
Imaging has traditionally been regarded by rheumatologists as a clinical tool to help diagnose and monitor the progress of various rheumatic diseases. This utilitarian perspective continues to be relevant in 2012, but with the introduction of advanced modalities, imaging has recently assumed another and equally important role as a non-invasive means to investigate joint pathology. Traditionally, what we know of the pathology of rheumatoid arthritis (RA) from imaging has come from plain radiography. This has led to a rather skewed emphasis on cortical bone, which by virtue of its calcium content is very clearly depicted on plain x-ray (XR). Clearly, erosion of cortical bone is the sine qua non of aggressive RA, and from the radiographic point of view, the bone underlying the cortex is much less informative, revealing only a degree of periarticular osteopenia in active disease . This may have contributed to the impression that rheumatoid bone was an inert scaffold, covered in most parts of the joint by hyaline cartilage (radiographically, a blank space) and surrounded and eroded by inflamed synovium (radiographically, soft tissue swelling). In a seminal study comparing joint histology from cadavers with post-mortem radiography, Resnick and Gmelich  provided the necessary 'proof' that the XR image of the joint was an accurate representation. Subsequent studies of the synovium, obtained via synovial biopsy and from surgical samples, were conducted from the 1970s to the 2000s by using increasingly sophisticated immunohistochemical techniques. These studies combined with radiography, as described above, resulted in the traditional view that the rheumatoid joint was attacked 'from the outside' by inflamed synovium, full of activated inflammatory cells releasing proinflammatory and bone-resorbing cytokines and thus 'burrowing down' through cartilage and bone to produce the rheumatoid erosion as summarized by Schett and Firestein .
Recently, this traditional view has been challenged, largely since the advent of magnetic resonance imaging (MRI) and its application to the imaging of RA. MRI provides a means to view the subchondral trabecular bone underneath the rheumatoid joint, an area that previously was largely invisible. Considerable evidence now suggests that rheumatoid erosions may also develop 'from the inside out', and attention is now being paid to the subchondral bone as an important site of pathology . This, in turn, has raised the question of whether the bone marrow could be implicated in this disease, with the alarming but exciting prospect that a complete conceptual overhaul is required. This article will review imaging data that shed light on this issue, including information from XR, MRI, and ultrasound (US) observational studies as well as recent randomized controlled trials.
MRI bone edema - common in inflammatory arthritis
The term 'bone marrow edema' (BME) was first used by Wilson and colleagues  in 1988 to describe bone marrow hyperintensities on T2-weighted (T2w) MRI images in patients with transient osteoporosis. However, use of the term 'edema' leaves much to be desired. It raises confusing questions in the clinician's mind about how edema could occur inside bone, a tissue that is clearly not distensible. What edema really means is 'tissue water' as the high T2w MRI signal is derived from protons in relatively free water molecules contained within cells (other than lipocytes) and blood vessels. These are concentrated in regions of inflammation, and for this reason, MRI scanning has become widely used for the detection of inflammatory lesions by using the sensitive T2W sequences where inflammation is detected as bright signal.
MRI BME occurs in many conditions . Florid BME with intense bright signal on T2w or STIR sequences is typical of osteomyelitis [7, 8]. In this situation, histology is well documented and an active inflammatory osteitis replaces the normal marrow fat . BME is also an important early feature of sacroiliitis occurring in the spondyloarthropathies. Appel and colleagues  described a small series of eight ankylosing spondylitis patients in whom bone biopsy was taken from the zygapophyseal joints and histological examination revealed osteitis corresponding to regions of MRI BME. BME has also been described in psoriatic arthritis , in which it may be associated with dactylitis , enthesitis, and especially arthritis mutilans . In osteoarthritis, BME lesions are somewhat different histologically, featuring marrow fat necrosis, fibrosis, and healing trabecular microfractures as described by Zanetti and Taljanovic [13, 14]. Thus, MRI BME is not disease-specific. There is a parallel with the radiographic sign of osteopenia, which may be associated with osteomalacia, osteoporosis, or, in its localized periarticular form, RA. However, BME has been found to have special significance in RA, not only as an indicator of joint inflammation but as a marker of bone pathology and future bone damage.
The first description of BME occurring at the RA wrist appeared in the radiology literature from Koenig and colleagues . It was initially thought to be rare , but in 1998 this was refuted by findings from a New Zealand (NZ) cohort of 42 patients with early RA , in which BME was scored in 64% of cases. Common sites were the lunate, triquetrum, and the capitate . Peterfy and colleagues  recently reviewed MRI findings from four multicenter randomized controlled trials, including data from 522 patients with RA, and showed that BME (referred to as osteitis) was most frequently scored at the navicular (scaphoid), lunate, capitate, and radius at the wrist and the 2nd and 3rd metacarpals at the fingers and had a bone involvement pattern similar to that of erosions. Others have since confirmed that BME is common in early as well as late RA, and estimates of frequency range between 34% and 68% [17, 19–21]. Ostendorf and colleagues  described BME at the hands in 9 of 25 patients with early RA (within 12 months of onset). The investigators also scanned 10 patients with very early disease at a median of 9 weeks from first symptoms and found that hand MRI scans were normal or showed tenosynovitis only but that MRI scans of the forefoot revealed BME at the metatarsophalangeal (MTP) joints in 70% of patients . This recalls the radiographic finding that the first site for development of bone erosions is the 5th MTP joint  and suggests the possibility that BME in RA might be a pre-erosive lesion.
MRI bone edema - a biomarker for aggressive erosive disease
What is the prognostic significance of the BME lesion? This question was addressed by the NZ RA cohort study, in which patients were followed 1, 2, 6, and 8 years after presentation [17, 22–24] clinically, radiographically, and by using 1.5-T contrast-enhanced MRI scans at 0, 1, and 6 years. Individual carpal bones affected by BME at baseline were examined for the presence of new MRI erosions at 1 and 6 years, and a strong association was discovered. At 1 year, 542 paired observations (from baseline and 1 year) were examined, and an odds ratio (OR) of 6.47 was derived for the likelihood that BME would be followed by MRI erosion . After 6 years, paired observations were available at 407 sites in 31 patients [23, 25]. An intriguingly similar OR of 6.5 predicted erosion from baseline BME . Additionally, the sum score for BME at the wrist predicted both components of the XR Sharp/van der Heijde score for joint damage , joint space narrowing (JSN) plus erosion, separately and together with an r2 value of 0.2. This indicates that 20% of the variance of the XR data (reflecting damage at both hands and feet) was predicted by an MRI scan of one wrist taken 6 years earlier. Interestingly, initial MRI BME scores (at one wrist) also predicted overall physical function in these patients at 6 years  and even tendon function after 8 years (chi-squared 15.3, P = 0.0005) . Taken together, the findings from this cohort were dramatic and suggested that MRI BME in early RA has a profound negative influence upon outcome, both within the bone (development of XR erosions), cartilage (JSN), and tendons and in terms of overall physical function. The logical conclusion is that something profoundly important is going on within the bone marrow in RA.
Chronological review of studies showing that magnetic resonance imaging bone marrow edema predicts erosive progression in rheumatoid arthritis
Association with erosion progression
Outcome measure (XR, MRI, or CT)
McQueen et al. 
In this NZ cohort, 42 patients with early RA were enrolled at presentation, within 6 months of symptom onset.
Baseline bone edema score predicted MRI erosion score at 1 year (OR = 6.47, P <0.001).
MRI erosion score at dominant wrist
Savnik et al. 
Danish cohort of 22 patients had RA for less than 3 years. Patients were followed at 1 year.
Presence of bone edema in wrist bones at baseline was the strongest individual predictor of bone erosions at 1 year (P <0.007).
MRI erosions at dominant wrist
McQueen et al. 
NZ cohort was reviewed at 6 years. Patients were treated with non-biologic DMARDs. MRI outcome data on 31 patients and XR outcome data on 34 patients are available.
Baseline bone edema score was only MRI feature on multivariate analysis to predict 6-year Sharp score (R2 = 0.20, P = 0.01). At each bone, OR (95% CI) for bone edema predicting MRI erosion was 6.5 (2.78 to 18.1).
XR erosion score at hands and feet and MRI erosion score
Palosaari et al. 
Twenty-seven patients with early RA had a disease duration of less than 12 months. Contrast-enhanced MRI data on 24 patients at 2 years are available.
Bone edema score was the only baseline variable to predict erosive progression at 2 years on multivariate regression (OR = 4.2, 95% CI = 1.3 to 13.8). At each bone, ORs (95% CIs) of predicted erosion at 1 and 2 years were 28 (11.7 to 67.1) and 14.9 (6.3 to 34.9), respectively.
MRI erosion score wrist
Haavardsholm et al. 
Eighty-four patients with RA had a disease duration of less than 1 year. Follow-up was at 1 year. Traditional DMARD therapy (plus anti-TNFs in two patients by 1 year) was used.
Baseline MRI bone edema score of more than 2 RAMRIS units was an independent predictor of both XR (OR = 2.77, 95% CI = 1.06 to 7.21) and MRI erosive progression.
MRI erosive progression at dominant wrist and XR erosive progression at the hands
Hetland et al. 
One hundred thirty patients with early RA had a disease duration of 3.3 years. Combination non-biologic DMARD therapy, including ciclosporin, or placebo was used. Two-year follow-up data are available.
Baseline bone edema score was the only independent predictor of 2-year change in Sharp score (multivariate linear regression): coefficient = 0.75 (95% CI = 0.55 to 0.94, P = 0.001).
XR erosion score at hands and feet
Mundwiler et al. 
Forty-six patients had a disease duration of less than 5 years. MRI and XR of 3rd, 4th, and 5th MTP joints of both feet were performed. Patients were treated with traditional and biologic DMARDs; 1- and 2-year data are available.
Bone edema predicted MRI erosions at 6 and 12 months with PPVs of 0.25 and 0.50 and NPVs of 0.99 and 0.99, respectively. At each bone, ORs for bone edema being followed by erosion were 34.2 and 68.0 at 6 and 12 months, respectively.
MRI erosion score at 3rd, 4th, and 5th MTP joints bilaterally
Hetland et al. 
In the same cohort as above (Hetland et al. ), 139 patients completed 5 years of follow-up. No treatment influence on erosion progression was noted. No biologics were used.
MRI bone edema was an independent predictor of XR progression (coefficient = 0.82, CI = 0.50 to 1.13, P <0.001). Bone edema explained 23% of the variation in the progression of the TSS (Pearson's r = 0.48).
Change in XR erosion score at hands and feet (TSS progression rate)
Døhn et al. 
Fifty-two patients with biologic-naïve RA and a disease duration of 7 years were followed for 12 months on anti-TNF therapy (adalimumab/methotrexate).
When baseline MRI bone edema was present versus not present, RR for erosive progression in the same bone on CT at 12 months was 3.8 (95% CI = 1.5 to 9.3, P = 0.004). If bone edema was 'ever present' versus 'never present', RR was 14.8 (95% CI = 4.3 to 50.7).
CT erosions at dominant wrist and 2nd to 5th MCP (site-by-site).
Bøyesen et al. 
Eighty-four patients with RA (same cohort as that of Haavardsholm et al. )
Baseline total MRI bone edema score predicted MRI erosive progression at 1 year with an OR of 1.28 (95% CI = 1.01 to 1.64, P = 0.04).
MRI erosive progression
MRI BME has also been found to be a strong predictor of evolution from undifferentiated inflammatory arthritis (UA) to RA by Danish and Japanese groups [36–38]. Duer-Jensen and colleagues  studied 116 patients with early UA and found that 23% developed definite RA over the course of 12 to 23 months. A prediction model was constructed from baseline factors. When this included MRI BME at the hand and wrist in combination with clinical hand arthritis, positivity for rheumatoid factor, and morning stiffness lasting more than 1 hour, the optimal model correctly identified outcome in 82% of the patients. An alternative model, which did not incorporate MRI BME, predicted RA with only 60% accuracy. BME was also an independent predictor of progression (not achieved by MRI synovitis score, anti-CCP status, or CRP). Tamai and colleagues [37, 38] also studied this question and described similar findings. They used a 1.5-T MRI system (as opposed to the 0.6-T unit of the Danish group) and studied a cohort of 129 patients with UA . The authors' prediction model contained, as explanatory variables, positivity for anti-CCP or IgM-RF or both, MRI-proven symmetric synovitis, and MRI BME or bone erosion or both. At 1-year follow-up, 71.3% of the patients who were positive for two of these variables at baseline had developed RA. However, of the 22 UA patients who were positive for both anti-CCP and MRI BME, all progressed to RA with a positive predictive value of 100% . These results confirm the diagnostic power of bone marrow edema as a biomarker.
What is the link between MRI BME, synovitis, and erosion?
Most of the studies mentioned above have included measures of synovitis, which, according to the traditional paradigm of rheumatoid pathology, is the precursor to bone erosion. The association between synovitis and BME was explored by Conaghan and colleagues  at the metacarpophalangeal joints. They found that MRI synovitis (increased synovial thickness) was greater in joints with BME than without and that both lesions responded to intra-articular corticosteroid. More recently, this group analyzed MRI results from the GO-FORWARD (Golimumab for Subjects with Active RA Despite Methotrexate) study, which investigated efficacy of the anti-tumor necrosis factor (anti-TNF) agent golimumab  and found that the CRP decrease associated with a therapeutic response paralleled reductions in both synovitis and BME. Most cohort data have indicated that these measures correlate strongly with each other and that they often occur together within the same joint, but the crucial question remains: which is the pre-erosive lesion? Or could it be that both contribute to subsequent bone damage ?
Mundwiler and colleagues  attempted to tease this out further in their study of MRI scans of the 3rd, 4th, and 5th MTP joints in 50 patients with RA. The authors found that the absence of BME made the formation of an MRI erosion over the course of 1 year highly unlikely (negative predictive value at 12 months of 0.99) but that having BME dramatically increased the likelihood that an erosion would form. On baseline scans, BME was accompanied by synovitis in all but one case. However, synovitis was an isolated finding in 52 MTP joints at baseline, and only 6% of these developed subsequent bone defects or erosions. These results suggest that coexistent BME could be what gives synovitis its apparent association with later erosion. However, many of these patients began anti-TNF therapy during the study and this could have had an independent influence. In the NZ cohort referred to above, MRI synovitis was predictive of erosions at 1 year (with an OR of 2.14 compared with 6.4 for BME), but by the time the cohort was followed out to 6 years, this effect had disappeared (whereas the influence of BME remained). The data from this group are particularly important as they did not receive anti-TNF agents, which could confound the issue due to their powerful erosion-suppression effect. Therefore, the NZ data may have more closely followed the natural history of RA.
US data related to synovitis are interesting to review here because grayscale synovial thickening has been associated with later bone erosion in some 12-month prognostic studies [34, 41], but the strongest association has been with time-integrated measures of synovial vascularity from power Doppler ultrasound (PDUS), as reported by both Naredo and colleagues  and Brown and colleagues . Clearly, using US alone does not allow bone edema, which is invisible to the US probe, to be monitored, but it is interesting to speculate whether those joints with the most vascular synovium and thus highest US Doppler activity could be those with the most active underlying osteitis. A recent paper by Boesen and colleagues  addressed this question. They investigated correlations between RAMRIS scores for bone edema and synovitis and the PDUS score at the wrist joints in 50 patients with RA. The strongest correlation was between the RAMRIS bone edema and PDUS scores (rho = 0.6, P <0.001). BME was confirmed to be a vascular lesion by Hodgson and colleagues  by using dynamic-enhanced MRI. Interestingly, those authors found this measure of BME to be more sensitive than the static RAMRIS bone edema score, suggesting that low-grade osteitis may sometimes be below the level of detection of standard MRI imaging (as has also been indicated by comparative MRI/histology studies; see 'MRI BME in RA represents osteitis' section below ).
Cartilage damage occurs late and in parallel with erosion
How does cartilage damage fit into the equation? A recent study examined cartilage loss at rheumatoid wrist joints by using MRI and compared this with a control group . Unexpectedly, cartilage thinning was very minor in the group with early RA (<2 years) and not significantly different from that of controls, but there was active BME and quite extensive carpal erosion in many of these patients. If the sequence of pathology is from synovitis to cartilage damage to bone erosion, then one would expect cartilage thinning to be an early lesion. Instead, this evidence suggests that the rheumatoid erosion has a bone-centered origin and that cartilage damage occurs as a separate consequence, a conclusion that was also proposed by van der Heijde  in a review of radiographic progression of RA joint damage. The author noted (of JSN and erosion) that 'these two processes often occur in parallel but joints in which erosions are present show a preference for progression of erosions and ... (in) joints with JSN present, there is a preference for worsening of JSN over development of erosions'.
MRI BME in RA represents osteitis
Could MRI BME and periarticular osteopenia be linked?
If a region of trabecular bone contains a cellular infiltrate that replaces marrow fat, then on MRI T2w or STIR sequences, BME will appear as described above. If bony trabeculae are undamaged, there will not be osteopenia, because the XR can detect the calcium in bone only and does not image soft tissue within the marrow. However, if bony trabeculae are thinned (for example, by an osteoclast-mediated resorptive process), then the two conditions could occur together and become superimposed . The histology of BME described by Dalbeth and colleagues  showed features consistent with this hypothesis as a marrow infiltrate of macrophages, lymphocytes, and plasma cells was found directly in contact with large numbers of osteoclasts sitting in resorption lacunae on bony trabeculae. Bøyesen and colleagues  investigated the link between radiographic and MRI bone changes in the Norwegian cohort of 84 patients mentioned above . As stated above, BME was an independent predictor of MRI erosive progression, but when bone mineral density (BMD) loss at 3 months was examined, there was only a trend towards this being associated with erosion progression. However, BMD was measured by digital XR radiogrammetry by using the method described by Hoff and colleagues , which estimates cortical bone at the centers of metacarpals II, III, and IV, and not trabecular bone in the periarticular region, where bone marrow edema tends to occur. de Rooy and colleagues  investigated the related issue of whether low BMD predicted the development of RA in patients with UA. The authors confirmed that patients with reduced BMD at the hands were more likely to develop RA with an OR of 6.1. This recalls the work of Tamai and colleagues  cited above, which showed that MRI BME in patients with UA predicts the later development of RA. Clearly, more work examining the immediate periarticular region and comparing BMD and MRI BME at that site would be interesting.
There are more data from quantitative histological studies of periarticular rheumatoid bone from the pre-MRI era. These revealed findings that were very similar to those described above , with regions of periarticular osteopenia featuring osteoclasts concentrated on trabeculae and an increase in the active osteoid surface in RA compared with OA specimens (12% versus 4.8%, P <0.001) . This study and others were summarized by Goldring and Gravallese  as revealing 'the presence in the marrow space of local aggregates of inflammatory cells, including macrophages and lymphocytes (with) .... an increase in resorption surfaces, which are often populated by osteoclasts'. The authors went on to remark that 'the absence of direct synovial interaction with the bone surfaces indicates that different cellular interactions are involved in the recruitment and activation of the bone resorbing cells' . It seems possible that MRI BME and radiographic periarticular osteopenia reflect two different faces of the same entity: the rheumatoid bone lesion. XRs reveal the trabecular resorption taking place, whereas MRI reveals the inflammatory infiltrate within the marrow space.
The influence of biologics on MRI BME (osteitis)
1. Anti-TNF therapy
If the rheumatoid bone lesion that is revealed on MRI as BME and that is histologically osteitis is pathologically important, then it would be expected to respond to therapy, especially therapy that stops the progression of bone erosions. A number of studies of anti-TNF agents have examined the question of regression of MRI synovitis and BME [40, 57]. Døhn and colleagues  examined 52 patients with erosive biologic-naïve RA by using MRI as well as other imaging during adalimumab/methotrexate combination therapy. As was the case for other non-biologic studies discussed already, baseline MRI BME predicted progression of computed tomography (CT) erosions with a relative risk of 3.8 (95% confidence interval of 1.5 to 9.3). At 12 months, MRI synovitis was registered in 95% of joints and BME in 20% of bones, but there was no significant change in MRI or US erosion scores, indicating that overall erosive progression was arrested. This effect was also apparent in the more recent MRI studies of golimumab therapy , in which both osteitis and synovitis persisted (but at reduced levels) despite virtual cessation of erosion. This throws a spanner in the works for both traditional and new hypotheses of erosion generation in RA, which assume synovitis or osteitis or both as the pre-erosive lesion. This has been referred to as the 'disconnect' and has been postulated to be due to a reduction in TNF-mediated RANKL signaling to osteoclasts, without which they are inactive and do not resorb bone . There is evidence for this from animal models; for example, a fusion protein of osteoprotegerin which inhibits RANK-RANKL interactions can prevent bone erosion in TNF-transgenic mice . Similarly, a study of denusomab, a RANKL-blocking monoclonal, revealed no significant clinical improvement in treated RA patients despite marked suppression of bone erosion on MRI and XR . Interestingly, radiographic JSN continued to progress in these patients despite the suppression of erosion, suggesting that a different mechanism may mediate this form of joint damage, as also proposed by van der Heijde and colleagues .
2. B-cell depletion
What happens to osteitis after treatment with B cell-depleting therapy, which is also known to halt the progression of XR erosions? This question was partly answered by the abstract that Peterfy and colleagues  submitted last year to the European League Against Rheumatism, in which MRI wrist scans from 185 patients in the Study of MabThera [Rituximab] in Patients with Rheumatoid Arthritis and Inadequate Response to Methotrexate (RA-SCORE) study were examined. These patients with RA were biologic-naïve and had responded inadequately to methotrexate. They were treated with rituximab/methotrexate or placebo/methotrexate, and MRI outcomes were assessed. A marked and significant reduction in osteitis (BME) was observed in rituximabtreated groups from weeks 12 to 24, and there was also a reduction in MRI synovitis scores. Consistent with earlier studies using XR erosions as an endpoint , there was also virtual cessation of erosion progression and JSN. The finding that depletion of B cells markedly reduced osteitis implies that the bone marrow B cell (or its offspring, the plasma cell) is likely to be intimately involved in the process of erosion. Could RANKL again be implicated in this scenario? Very recently, Boumans and colleagues  explored this by using synovial biopsy specimens to evaluate RANKL expression in osteoclast precursors present within the synovium. Sixteen weeks after rituximab/methotrexate treatment, they found a 99% decrease in RANKL-positive osteoclast precursors (P = 0.02) and a 37% decrease in RANKL expression in the synovium. Presumably, a very similar process could be taking place in the subchondral bone marrow, but that tissue is much more difficult to obtain.
3. Interleukin-6R inhibition and T-cell costimulation blockade
In a study investigating the efficacy of interleukin-6R inhibition in 31 patients with RA, RAMRIS osteitis (BME) scores fell markedly among patients on tocilizumab, both as monotherapy and combined with methotrexate . The authors noted that using MRI osteitis as an outcome measure allowed a therapeutic effect to be detected at 12 weeks, much earlier than the point at which radiographic abnormalities would have become apparent. Another study took things one step further by investigating patients with pre-RA (patients with UA who were anti-CCP-positive with synovitis at two joints). MRI synovitis, osteitis, and erosion were monitored during treatment with abatacept or placebo . At 6 months, osteitis scores in the group had improved almost 70% from baseline, but in those receiving placebo, the mean score increased by 41%. Thus, the finding that osteitis is an important pre-erosive lesion has now been adopted by pharmaceutical companies and is being employed to show efficacy of biologic therapies much earlier than was previously possible. This should translate to a more rapid assessment of response and overall improved patient management.
In summary, over the last 15 years, studies investigating MRI BME have provided new insight into the pathogenesis of RA. There is firm evidence from many groups that BME is the strongest of many conventional and imaging biomarkers for prediction of erosive progression. It is also a predictor of an aggressive RA phenotype associated with functional decline and the transition from UA to RA. Histologically, in late disease, BME has been shown to be osteitis, comprising a lymphoplasmacytic inflammatory infiltrate within the marrow, directly adjacent to osteoclasts sitting in lacunae on trabecular bone. Resorption of bony trabeculae is likely to result in the radiographic sign of periarticular osteopenia, and marrow infiltration by osteitis with resultant osteoclast activation could be driving this process. MRI studies of the therapeutic response to biologics have shown osteitis to be responsive to therapy with anti-TNF, B cell depleting therapy, and other biologic agents. Thus, a whole new dimension of rheumatoid pathology now needs consideration, and the bone marrow compartment is at center stage.
This article is part of the series on Is rheumatoid arthritis a bone marrow disease? Other articles in this series can be found at http://arthritis-research.com/series/marrow
anti-cyclic citrullinated peptide
anti-tumor necrosis factor
bone mineral density
bone marrow edema
joint space narrowing
magnetic resonance imaging
power Doppler ultrasound
rheumatoid arthritis magnetic resonance imaging score
short tau inversion recovery
total Sharp score
- Brook A, Corbett M: Radiographic changes in early rheumatoid disease. Ann Rheum Dis. 1977, 36: 71-73. 10.1136/ard.36.1.71.PubMed CentralView ArticlePubMedGoogle Scholar
- Resnick D, Gmelich JT: Bone fragmentation in the rheumatoid wrist: radiographic and pathologic considerations. Radiology. 1975, 114: 315-321.View ArticlePubMedGoogle Scholar
- Schett G, Firestein GS: Mr Outside and Mr Inside: classic and alternative views on the pathogenesis of rheumatoid arthritis. Ann Rheum Dis. 2010, 69: 787-789. 10.1136/ard.2009.121657.View ArticlePubMedGoogle Scholar
- Wilson AJ, Murphy WA, Hardy DC, Totty WG: Transient osteoporosis: transient bone marrow edema?. Radiology. 1988, 167: 757-760.View ArticlePubMedGoogle Scholar
- Peterfy CG: Magnetic resonance imaging of the wrist in rheumatoid arthritis. Semin Musculoskelet Radiol. 2001, 5: 275-288. 10.1055/s-2001-17549.View ArticlePubMedGoogle Scholar
- McQueen FM, Ostendorf B: What is MRI bone oedema in rheumatoid arthritis and why does it matter?. Arthritis Res Ther. 2006, 8: 222-225. 10.1186/ar2075.PubMed CentralView ArticlePubMedGoogle Scholar
- Craig JG, Amin MB, Wu K, Eyler WR, van Holsbeeck MT, Bouffard JA, Shirazi K: Osteomyelitis of the diabetic foot: MR imaging-pathologic correlation. Radiology. 1997, 203: 849-855.View ArticlePubMedGoogle Scholar
- Poh YJ, Dalbeth N, Doyle A, McQueen FM: MRI bone oedema is not a major feature of gout unless there is concomitant osteomyelitis: ten year findings from a high prevalence population. J Rheumatol. 2011, 38: 2475-2481. 10.3899/jrheum.110477.View ArticlePubMedGoogle Scholar
- Appel H, Loddenkemper C, Grozdanovic Z, Ebhardt H, Dreimann M, Hempfing A, Stein H, Metz-Stavenhagen P, Rudwaleit M, Sieper J: Correlation of histopathological findings and magnetic resonance imaging in the spine of patients with ankylosing spondylitis. Arthritis Res Ther. 2006, 8: R143-10.1186/ar2035.PubMed CentralView ArticlePubMedGoogle Scholar
- McQueen F, Lassere M, Ostergaard M: Magnetic resonance imaging in psoriatic arthritis: a review of the literature. Arthritis Res Ther. 2006, 8: 207-10.1186/ar1934.PubMed CentralView ArticlePubMedGoogle Scholar
- Healy PJ, Groves C, Chandramohan M, Helliwell PS: MRI changes in psoriatic dactylitis - extent of pathology, relationship to tenderness and correlation with clinical indices. Rheumatology. 2008, 47: 92-95. 10.1093/rheumatology/kem315.View ArticlePubMedGoogle Scholar
- Tan YM, Østergaard M, Doyle A, Dalbeth N, Lobo M, Reeves Q, Robinson E, Taylor WJ, Jones PB, Pui K, Lee J, McQueen FM: MRI bone oedema scores are higher in the arthritis mutilans form of psoriatic arthritis and correlate with high radiographic scores for joint damage. Arthritis Res Ther. 2009, 11: R2-10.1186/ar2586.PubMed CentralView ArticlePubMedGoogle Scholar
- Zanetti M, Bruder E, Romero J, Hodler J: Bone marrow edema pattern in osteoarthritic knees: correlation between MR imaging and histologic findings. Radiology. 2000, 215: 835-840.View ArticlePubMedGoogle Scholar
- Taljanovic MS, Graham AR, Benjamin JB, Gmitro AF, Krupinski EA, Schwartz SA, Hunter TB, Resnick DL: Bone marrow edema pattern in advanced hip osteoarthritis: quantitative assessment with magnetic resonance imaging and correlation with clinical examination, radiographic findings, and histopathology. Skeletal Radiol. 2008, 37: 423-431. 10.1007/s00256-008-0446-3.View ArticlePubMedGoogle Scholar
- Koenig H, Lucas D, Meissner R: The wrist: a preliminary report on high-resolution MR imaging. Radiology. 1986, 160: 463-467.View ArticlePubMedGoogle Scholar
- Jevtic V, Watt I, Rozman B, Kos-Golja M, Demsar F, Jarh O: Distinctive radiological features of small hand joints in rheumatoid arthritis and seronegative spondyloarthritis demonstrated by contrast-enhanced (Gd-DTPA) magnetic resonance imaging. Skeletal Radiol. 1995, 24: 351-355.View ArticlePubMedGoogle Scholar
- McQueen FM, Stewart N, Crabbe J, Robinson E, Yeoman S, Tan PL, McLean L: Magnetic resonance imaging of the wrist in early rheumatoid arthritis reveals a high prevalence of erosions at four months after symptom onset. Ann Rheum Dis. 1998, 57: 350-356. 10.1136/ard.57.6.350.PubMed CentralView ArticlePubMedGoogle Scholar
- Peterfy CG, Countryman P, Gabriele A, Shaw T, Anisfeld A, Tsuji W, Olech E, Gaylis NB, Conaghan PG, Strand V, Dicarlo J: Magnetic resonance imaging in rheumatoid arthritis clinical trials: emerging patterns based on recent experience. J Rheumatol. 2011, 38: 2023-2030. 10.3899/jrheum.110418.View ArticlePubMedGoogle Scholar
- Ostendorf B, Scherer A, Mödder U, Schneider M: Diagnostic value of magnetic resonance imaging of the forefeet in early rheumatoid arthritis when findings on imaging of the metacarpophalangeal joints of the hands remain normal. Arthritis Rheum. 2004, 50: 2094-2102. 10.1002/art.20314.View ArticlePubMedGoogle Scholar
- Savnik A, Malmskov H, Thomsen HS, Graff LB, Nielsen H, Danneskiold-Samsøe B, Boesen J, Bliddal H: Magnetic resonance imaging of the wrist and finger joints in patients with inflammatory joint diseases. J Rheumatol. 2001, 28: 2193-2200.PubMedGoogle Scholar
- Mundwiler ML, Maranian P, Brown DH, Silverman JM, Wallace D, Khanna D, Louie J, Furst DE, Weisman MH: The utility of MRI in predicting radiographic erosions in the metatarsophalangeal joints of the rheumatoid foot: a prospective longitudinal cohort study. Arthritis Res Ther. 2009, 11: R94-10.1186/ar2737.PubMed CentralView ArticlePubMedGoogle Scholar
- McQueen FM, Stewart N, Crabbe J, Robinson E, Yeoman S, Tan PL, McLean L: Magnetic resonance imaging of the wrist in early rheumatoid arthritis reveals progression of erosions despite clinical improvement. Ann Rheum Dis. 1999, 58: 156-163. 10.1136/ard.58.3.156.PubMed CentralView ArticlePubMedGoogle Scholar
- McQueen FM, Benton N, Perry D, Crabbe J, Robinson E, Yeoman S, McLean L, Stewart N: Bone edema scored on magnetic resonance imaging scans of the dominant carpus at presentation predicts radiographic joint damage of the hands and feet six years later in patients with rheumatoid arthritis. Arthritis Rheum. 2003, 48: 1814-1827. 10.1002/art.11162.View ArticlePubMedGoogle Scholar
- Zheng S, Robinson E, Yeoman S, Stewart N, Crabbe J, Rouse J, McQueen FM: MRI bone oedema predicts eight year tendon function at the wrist but not the requirement for orthopaedic surgery in rheumatoid arthritis. Ann Rheum Dis. 2006, 65: 607-611. 10.1136/ard.2005.043323.PubMed CentralView ArticlePubMedGoogle Scholar
- McQueen FM, Benton N, Crabbe J, Robinson E, Yeoman S, McLean L, Stewart N: What is the fate of erosions in early rheumatoid arthritis? Tracking individual lesions using × rays and magnetic resonance imaging over the first two years of disease. Ann Rheum Dis. 2001, 60: 859-868.PubMed CentralPubMedGoogle Scholar
- van der Heijde DM, van Riel PL, Nuver-Zwart IH, Gribnau FW, vad de Putte LB: Effects of hydroxychloroquine and sulphasalazine on progression of joint damage in rheumatoid arthritis. Lancet. 1989, 1: 1036-1038.View ArticlePubMedGoogle Scholar
- Benton N, Stewart N, Crabbe J, Robinson E, Yeoman S, McQueen FM: MRI of the wrist in early rheumatoid arthritis can be used to predict functional outcome at 6 years. Ann Rheum Dis. 2004, 63: 555-561. 10.1136/ard.2003.011544.PubMed CentralView ArticlePubMedGoogle Scholar
- Haavardsholm EA, Bøyesen P, Østergaard M, Schildvold A, Kvien TK: Magnetic resonance imaging findings in 84 patients with early rheumatoid arthritis: bone marrow oedema predicts erosive progression. Ann Rheum Dis. 2008, 67: 794-800. 10.1136/ard.2007.071977.View ArticlePubMedGoogle Scholar
- Hetland ML, Ejbjerg B, Hørslev-Petersen K, Jacobsen S, Vestergaard A, Jurik AG, Stengaard-Pedersen K, Junker P, Lottenburger T, Hansen I, Andersen LS, Tarp U, Skjødt H, Pedersen JK, Majgaard O, Svendsen AJ, Ellingsen T, Lindegaard H, Christensen AF, Vallø J, Torfing T, Narvestad E, Thomsen HS, Ostergaard M, CIMESTRA study group: MRI bone oedema is the strongest predictor of subsequent radiographic progression in early rheumatoid arthritis. Results from a 2-year randomised controlled trial (CIMESTRA). Ann Rheum Dis. 2009, 68: 384-390. 10.1136/ard.2008.088245.View ArticlePubMedGoogle Scholar
- Hetland ML, Stengaard-Pedersen K, Junker P, Østergaard M, Ejbjerg BJ, Jacobsen S, Lottenburger T, Hansen I, Tarp U, Andersen LS, Svendsen A, Pedersen JK, Lauridsen UB, Ellingsen T, Lindegaard H, Pødenphant J, Vestergaard A, Jurik AG, Hørslev-Petersen K, CIMESTRA study group: Radiographic progression and remission rates in early rheumatoid arthritis - MRI bone oedema and anti-CCP predicted radiographic progression in the 5-year extension of the double-blind randomised CIMESTRA trial. Ann Rheum Dis. 2010, 69: 1789-1795. 10.1136/ard.2009.125534.View ArticlePubMedGoogle Scholar
- Østergaard M, Peterfy C, Conaghan P, McQueen F, Bird P, Ejbjerg B, Shnier R, O'Connor P, Klarlund M, Emery P, Genant H, Lassere M, Edmonds J: OMERACT Rheumatoid Arthritis Magnetic Resonance Imaging Studies. Core set of MRI acquisitions, joint pathology definitions, and the OMERACT RA-MRI scoring system. J Rheumatol. 2003, 30: 1385-1386.PubMedGoogle Scholar
- Hetland ML, Stengaard-Pedersen K, Junker P, Lottenburger T, Hansen I, Andersen LS, Tarp U, Svendsen A, Pedersen JK, Skjødt H, Lauridsen UB, Ellingsen T, Hansen GV, Lindegaard H, Vestergaard A, Jurik AG, Østergaard M, Hørslev-Petersen K, CIMESTRA study group: Aggressive combination therapy with intra-articular glucocorticoid injections and conventional disease-modifying anti-rheumatic drugs in early rheumatoid arthritis: second-year clinical and radiographic results from the CIMESTRA study. Ann Rheum Dis. 2008, 67: 815-822. 10.1136/ard.2007.076307.View ArticlePubMedGoogle Scholar
- Palosaari K, Vuotila J, Takalo R, Jartti A, Niemelä RK, Karjalainen A, Haapea M, Soini I, Tervonen O, Hakala M: Bone oedema predicts erosive progression on wrist MRI in early RA--a 2-yr observational MRI and NC scintigraphy study. Rheumatology. 2006, 45: 1542-1548. 10.1093/rheumatology/kel137.View ArticlePubMedGoogle Scholar
- Bøyesen P, Haavardsholm EA, van der Heijde D, Østergaard M, Hammer HB, Sesseng S, Kvien TK: Prediction of MRI erosive progression: a comparison of modern imaging modalities in early rheumatoid arthritis patients. Ann Rheum Dis. 2011, 70: 176-179. 10.1136/ard.2009.126953.View ArticlePubMedGoogle Scholar
- Savnik A, Bliddal H, Nyengaard JR, Thomsen HS: MRI of the arthritic finger joints: synovial membrane volume determination, a manual vs a stereologic method. Eur Radiol. 2002, 12: 94-98. 10.1007/s003300100986.View ArticlePubMedGoogle Scholar
- Duer-Jensen A, Hørslev-Petersen K, Hetland ML, Bak L, Ejbjerg BJ, Hansen MS, Johansen JS, Lindegaard HM, Vinterberg H, Møller JM, Østergaard M: Bone edema on magnetic resonance imaging is an independent predictor of rheumatoid arthritis development in patients with early undifferentiated arthritis. Arthritis Rheum. 2011, 63: 2192-2202. 10.1002/art.30396.View ArticlePubMedGoogle Scholar
- Tamai K Yamato M, Yamaguchi T, Ohno W: Bone marrow oedema determined by MRI reflects severe disease status in patients with early-stage rheumatoid arthritis. Ann Rheum Dis. 2006, 65 (Suppl II): 629-Google Scholar
- Tamai M, Kawakami A, Uetani M, Takao S, Arima K, Iwamoto N, Fujikawa K, Aramaki T, Kawashiri SY, Ichinose K, Kamachi M, Nakamura H, Origuchi T, Ida H, Aoyagi K, Eguchi K: A prediction rule for disease outcome in patients with undifferentiated arthritis using magnetic resonance imaging of the wrists and finger joints and serologic autoantibodies. Arthritis Rheum. 2009, 61: 772-778. 10.1002/art.24711.View ArticlePubMedGoogle Scholar
- Conaghan PG, O'Connor P, McGonagle D, Astin P, Wakefield RJ, Gibbon WW, Quinn M, Karim Z, Green MJ, Proudman S, Isaacs J, Emery P: Elucidation of the relationship between synovitis and bone damage: a randomized magnetic resonance imaging study of individual joints in patients with early rheumatoid arthritis. Arthritis Rheum. 2003, 48: 64-71. 10.1002/art.10747.View ArticlePubMedGoogle Scholar
- Conaghan PG, Emery P, Østergaard M, Keystone EC, Genovese MC, Hsia EC, Xu W, Rahman MU: Assessment by MRI of inflammation and damage in rheumatoid arthritis patients with methotrexate inadequate response receiving golimumab: results of the GO-FORWARD trial. Ann Rheum Dis. 2011, 70: 1968-1974. 10.1136/ard.2010.146068.PubMed CentralView ArticlePubMedGoogle Scholar
- Taylor PC, Steuer A, Gruber J, Cosgrove DO, Blomley MJ, Marsters PA, Wagner CL, McClinton C, Maini RN: Comparison of ultrasonographic assessment of synovitis and joint vascularity with radiographic evaluation in a randomized, placebo-controlled study of infliximab therapy in early rheumatoid arthritis. Arthritis Rheum. 2004, 50: 1107-1116. 10.1002/art.20123.View ArticlePubMedGoogle Scholar
- Naredo E, Möller I, Cruz A, Carmona L, Garrido J: Power Doppler ultrasonographic monitoring of response to anti-tumor necrosis factor therapy in patients with rheumatoid arthritis. Arthritis Rheum. 2008, 58: 2248-2256. 10.1002/art.23682.View ArticlePubMedGoogle Scholar
- Brown AK, Conaghan PG, Karim Z, Quinn MA, Ikeda K, Peterfy CG, Hensor E, Wakefield RJ, O'Connor PJ, Emery P: An explanation for the apparent dissociation between clinical remission and continued structural deterioration in rheumatoid arthritis. Arthritis Rheum. 2008, 58: 2958-2967. 10.1002/art.23945.View ArticlePubMedGoogle Scholar
- Boesen M, Ellegaard K, Boesen L, Cimmino MA, Jensen PS, Terslev L, Torp-Pedersen S, Danneskiold-Samsøe B, Bliddal H: Ultrasound Doppler score correlates with OMERACT RAMRIS bone marrow oedema and synovitis score in the wrist joint of patients with rheumatoid arthritis. Ultraschall Med. 2011.Google Scholar
- Hodgson R, Grainger A, O'Connor P, Barnes T, Connolly S, Moots R: Dynamic contrast enhanced MRI of bone marrow oedema in rheumatoid arthritis. Ann Rheum Dis. 2008, 67: 270-272. 10.1136/ard.2007.077271.View ArticlePubMedGoogle Scholar
- McQueen FM, Gao A, Ostergaard M, King A, Shalley G, Robinson E, Doyle A, Clark B, Dalbeth N: High grade MRI bone oedema is common within the surgical field in rheumatoid arthritis patients undergoing joint replacement and is associated with osteitis in subchondral bone. Ann Rheum Dis. 2007, 66: 1581-1587. 10.1136/ard.2007.070326.PubMed CentralView ArticlePubMedGoogle Scholar
- McQueen F, Clarke A, McHaffie A, Reeves Q, Williams M, Robinson E, Dong J, Chand A, Mulders D, Dalbeth N: Assessment of cartilage loss at the wrist in rheumatoid arthritis using a new MRI scoring system. Ann Rheum Dis. 2010, 69: 1971-1975. 10.1136/ard.2009.127324.View ArticlePubMedGoogle Scholar
- van der Heijde D: Erosions versus joint space narrowing in rheumatoid arthritis: what do we know?. Ann Rheum Dis. 2011, 70 (Suppl 1): i116-118. 10.1136/ard.2010.140525.View ArticlePubMedGoogle Scholar
- Jimenez-Boj E, Nöbauer-Huhmann I, Hanslik-Schnabel B, Dorotka R, Wanivenhaus AH, Kainberger F, Trattnig S, Axmann R, Tsuji W, Hermann S, Smolen J, Schett G: Bone erosions and bone marrow edema as defined by magnetic resonance imaging reflect true bone marrow inflammation in rheumatoid arthritis. Arthritis Rheum. 2007, 56: 1118-1124. 10.1002/art.22496.View ArticlePubMedGoogle Scholar
- Dalbeth N, Smith T, Gray S, Doyle A, Antill P, Lobo M, Robinson E, King A, Cornish J, Shalley G, Gao A, McQueen FM: Cellular characterisation of magnetic resonance imaging bone oedema in rheumatoid arthritis; implications for pathogenesis of erosive disease. Ann Rheum Dis. 2009, 68: 279-282. 10.1136/ard.2008.096024.View ArticlePubMedGoogle Scholar
- McQueen F: A B cell explanation for autoimmune disease: the forbidden clone returns. Postgrad Med J. 2012, 88: 226-233. 10.1136/postgradmedj-2011-130364.View ArticlePubMedGoogle Scholar
- McQueen FM, Dalbeth N: Predicting joint damage in rheumatoid arthritis using MRI scanning. Arthritis Res Ther. 2009, 11: 124-10.1186/ar2778.PubMed CentralView ArticlePubMedGoogle Scholar
- Hoff M, Haugeberg G, Odegård S, Syversen S, Landewé R, van der Heijde D, Kvien TK: Cortical hand bone loss after 1 year in early rheumatoid arthritis predicts radiographic hand joint damage at 5-year and 10-year follow-up. Ann Rheum Dis. 2009, 68: 324-329. 10.1136/ard.2007.085985.View ArticlePubMedGoogle Scholar
- de Rooy DP, Kälvesten J, Huizinga TW, van der Helm-van Mil AH: Loss of metacarpal bone density predicts RA development in recent-onset arthritis. Rheumatology. 2012, 51: 1037-1041. 10.1093/rheumatology/ker435.View ArticlePubMedGoogle Scholar
- Shimizu S, Shiozawa S, Shiozawa K, Imura S, Fujita T: Quantitative histologic studies on the pathogenesis of periarticular osteoporosis in rheumatoid arthritis. Arthritis Rheum. 1985, 28: 25-31. 10.1002/art.1780280105.View ArticlePubMedGoogle Scholar
- Goldring SR, Gravallese EM: Mechanisms of bone loss in inflammatory arthritis: diagnosis and therapeutic implications. Arthritis Res. 2000, 2: 33-37. 10.1186/ar67.PubMed CentralView ArticlePubMedGoogle Scholar
- Døhn UM, Ejbjerg B, Boonen A, Hetland ML, Hansen MS, Knudsen LS, Hansen A, Madsen OR, Hasselquist M, Møller JM, Ostergaard M: No overall progression and occasional repair of erosions despite persistent inflammation in adalimumab-treated rheumatoid arthritis patients: results from a longitudinal comparative MRI, ultrasonography, CT and radiography study. Ann Rheum Dis. 2011, 70: 252-258. 10.1136/ard.2009.123729.View ArticlePubMedGoogle Scholar
- McQueen F, Naredo E: The 'disconnect' between synovitis and erosion in rheumatoid arthritis: a result of treatment or intrinsic to the disease process itself?. Ann Rheum Dis. 2011, 70: 241-244. 10.1136/ard.2010.139535.View ArticlePubMedGoogle Scholar
- Sato K, Takayanagi H: Osteoclasts, rheumatoid arthritis, and osteoimmunology. Curr Opin Rheumatol. 2006, 18: 419-426. 10.1097/01.bor.0000231912.24740.a5.View ArticlePubMedGoogle Scholar
- Cohen SB, Dore RK, Lane NE, Ory PA, Peterfy CG, Sharp JT, van der Heijde D, Zhou L, Tsuji W, Newmark R, Denosumab Rheumatoid Arthritis Study Group: Denosumab treatment effects on structural damage, bone mineral density, and bone turnover in rheumatoid arthritis: a twelve-month, multicenter, randomized, double-blind, placebo-controlled, phase II clinical trial. Arthritis Rheum. 2008, 58: 1299-1309. 10.1002/art.23417.View ArticlePubMedGoogle Scholar
- Peterfy C, Emery P, Tak PP, Østergaard M, DiCarlo J, Otsa K, Navarro Sarabi F, Pavelka K, Preston K, Shaw T, Bagnard MA, Gabriele A: Rituximab (RTX) plus methotrexate (MTX) prevents bone erosion and joint space narrowing (jsn) and reduces synovitis, osteitis as shown on MRI: results from a randomised, placebo-controlled clinical trial on patients with rheumatoid arthritis (RA-score) [abstract]. Ann Rheum Dis. 2011, 70 (Suppl 3): 152-Google Scholar
- Tak PP, Rigby WF, Rubbert-Roth A, Peterfy CG, van Vollenhoven RF, Stohl W, Hessey E, Chen A, Tyrrell H, Shaw TM, IMAGE Investigators: Inhibition of joint damage and improved clinical outcomes with rituximab plus methotrexate in early active rheumatoid arthritis: the IMAGE trial. Ann Rheum Dis. 2011, 70: 39-46. 10.1136/ard.2010.137703.View ArticlePubMedGoogle Scholar
- Boumans MJ, Thurlings RM, Yeo L, Scheel-Toellner D, Vos K, Gerlag DM, Tak PP: Rituximab abrogates joint destruction in rheumatoid arthritis by inhibiting osteoclastogenesis. Ann Rheum Dis. 2012, 71: 108-113. 10.1136/annrheumdis-2011-200198.View ArticlePubMedGoogle Scholar
- Troum OM, Peterfy CG, Kaine JL, Chung CA, Olech E, Conaghan PG: Baseline CRP predicts early improvement in synovitis, osteitis, and erosion on MRI in RA patients treated with tocilizumab: results from the ACT-RAY MRI substudy. Arthritis Rheum. 2010, 62 (Suppl 10): 120-Google Scholar
- Peterfy C, Durez P, DiCarlo J, Becker JC, Vratsanos G, Overfield S, Qi K: Abatacept reduces osteitis and inhibits bone erosion in anti-CCP2 positive patients with synovitis at high risk of developing RA. Arthritis Rheum. 2009, 60 (Suppl 10): 1690-Google Scholar