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ID PMID Title PublicationDate abstract
20335001 Cricothyroid joint abnormalities in patients with rheumatoid arthritis. 2010 Nov The objective of this study was to assess structural and functional abnormalities of the cricothyroid joint (CTJ) in patients with advanced rheumatoid arthritis (RA). A total of 19 subjects--11 patients with advanced RA and eight normal controls--were considered. All subjects underwent laryngeal endoscopy, acoustic analysis, and high-resolution computerized tomography (HRCT). Vocal symptoms, such as hoarseness, loss of range, vocal fatigue, and dyspnea were inquired and acoustic parameters, mainly pitch range, fundamental frequency, habitual pitch, perturbation parameters, and noise-to-harmonic ratio (NHR) and voice turbulence index were measured. Frequencies and means were calculated for categorical and continuous variables. Cases and controls were compared with respect to acoustic analysis, HRCT findings and laryngeal symptoms using nonparametric tests, Mann-Whitney U test for continuous variables and Fishers exact test for categorical variables. Almost half of the patients with RA had loss range and two-thirds had vocal fatigue. Thirty-six percent experienced hoarseness compared with 25% in the control group. 9.1% had decrease in vocal fold mobility and 27% had moderate/severe edema of the vocal folds/arytenoids compared with none in the control group. HRCT showed narrowing in the CTJ in 81.8% and ankylosis in 9.1% compared with none in the control group. 45.5% had an increase in the CTJ density compared with 12.5% in the control group. Acoustic analysis revealed significant decrease in pitch range and maximum phonation time (MPT) and significant increase in perturbation parameters. CTJ is commonly affected in patients with RA. Functional disabilities are crucial especially in professional voice users. Proper awareness is important for early detection and intervention.
18688791 Piloting education days for patients with early rheumatoid arthritis and their partners: a 2009 Mar OBJECTIVES: To develop, pilot, refine and reassess an education day presented by a rheumatology multidisciplinary team (MDT) for recently diagnosed (less than six months) rheumatoid arthritis (RA) patients and their partners/carers. METHODS: A patient education day was developed drawing on an assessment of local patient educational needs and preferences and input from a rheumatology MDT. Feedback from the first education day (2004) (Day 1; 12 patients; age range 19-63 years (median 46); 10 of whom were accompanied by a partner) informed the development of a second education day (2005) (Day 2; 19 patients; age range 36-75 years (median 57.5); 13 of whom were accompanied by a partner). Participants completed evaluation forms on both days and at follow-up between six and seven weeks later, rating each session on a 5-point scale on dimensions of 'informative', 'useful', 'interesting' and 'enjoyable'. A global rating of the day's 'usefulness' was completed at the end of each day on a 10-point scale. Participants were asked to write comments on each session and on aspects of the entire day. RA knowledge, and general and RA-specific self-efficacy were also measured on day 2 (and at follow-up) using the 12-item Patient Knowledge Questionnaire, the 10-item generalized self-efficacy scale and a four-item RA-specific self-efficacy scale. Both qualitative and quantitative methodologies were used in the analysis. RESULTS: Ratings for individual sessions were all high, with no session being rated below 4 out of 5 (1 = 'totally disagree' to 5 = 'totally agree') on both days. The majority of patients (84%) and their partners (57%) responded to the follow-up. Many had used the information package distributed on the day. Some patients and their partners reported positive changes in RA management. Although patient knowledge did not increase significantly (medians 11 at both time points, p = 0.054) (Day 2), RA self-efficacy improved (baseline 11 and 14, respectively), suggesting that patients were more confident in managing their condition (p = 0.010). CONCLUSIONS: The development of this 'local' education and information intervention was carried out in line with Medical Research Council guidelines, and the lessons learned from Day 1 informed further development for Day 2. A one-day format for education of early RA involving the rheumatology MDT was rated highly by participants and warrants further examination. Although this study was a small 'local' intervention, its strengths are that it informs the possibility of wider developments of this kind using a MDT.
20337045 [Diagnostic value of glucose-6-phosphate isomerase in rheumatoid arthritis patients: syste 2010 Feb In order to evaluate the diagnostic accuracy of glucose-6-phosphate isomerase in patients with rheumatoid arthritis, retrieval was performed using the data bases of Medline, Embase, Cochrane library, Cmcc and Cbmdisc (1990 to 2007). We included the articles which reported the studies of GPI measured by enzyme-linked immunosorbent assay in the diagnosis of RA patients. Then we reviewed 15 article and used RevMan Software for analysis; the heterogeneity among the articles was determined to be high (chi2 = 191.65, P < 0.00001). When we analyzed the 5 articles wherein serum was used as the standard, we noticed homogeneity (chi2 = 6.97, P = 0.14). The summary sensitivity was 25%; the summary specificity was 80%; the area under the curve was 0.6279. Our study demonstrated that GPI exhibited high specificity and low sensitivity in diagnosing RA cases. We suggest that GPI be used in conjunction with some assay or other that is characterized by high sensitivity.
20954369 [A case of diffuse alveolar hemorrhage occurring during the course of rheumatoid arthritis 2010 Sep A 70-year-old woman, who underwent treatment with prednisolone and methotrexate for rheumatoid arthritis, was admitted to our hospital due to rapidly progressive dyspnea. A chest CT scan showed diffuse ground-glass opacities and reticulonodular shadows in both lungs. Intubation was performed due to severe hypoxia. The color of the bronchoalveolar lavage, using three sequential aliquots, became progressively more reddish, suggesting alveolar hemorrhage. Based on this, we made a diagnosis of diffuse alveolar hemorrhage. To the best of our knowledge, few studies have reported cases of diffuse alveolar hemorrhage associated with rheumatoid arthritis as an underlying disease. We consider that diffuse alveolar hemorrhage may occur as a complication of rheumatoid arthritis.
19796386 Positive anti-citrullinated protein antibody status and small joint arthritis are consiste 2009 INTRODUCTION: The current 1987 American College of Rheumatology (ACR) classification criteria for rheumatoid arthritis (RA) have proven less useful in early arthritis. The objective of this study was to identify and compare predictors of three relevant outcomes of chronic arthritis in a cohort of very early arthritis patients. METHODS: The Norwegian Very Early Arthritis Cohort (NOR-VEAC) includes adult patients with at least one swollen joint of < or = 16 weeks' duration. Patients are followed for 2 years with comprehensive clinical and laboratory examinations. Logistic regression analyses were performed to determine independent predictors of three outcomes: persistent synovitis, prescription of disease-modifying anti-rheumatic drugs (DMARDs), and established clinical RA diagnosis within one year. RESULTS: Of 384 patients eligible for one year follow-up (56.3% females, mean (SD) age 45.8 (14.7) years, median (IQR) duration of arthritis 31 (10-62) days), 14.4% were anti-CCP2 positive, and 11.2% were IgM RF positive. 98 patients (25.5%) had persistent synovitis, 106 (27.6%) had received DMARD treatment during follow-up, while 68 (17.7%) were diagnosed with RA. Consistent independent predictors across all three outcomes were positive anti-citrullinated protein antibody (ACPA) status (odds ratio (OR) 3.2, 5.6 and 19.3), respectively, and small joint arthritis (proximal interphalangeal joint (PIP), metacarpo-phalangeal joint (MCP), and/or metatarso-phalangeal joint (MTP) joint swelling) (OR 1.9, 3.5, and 3.5, respectively). CONCLUSIONS: Positive ACPA status and small joint arthritis were consistent predictors of three relevant outcomes of chronic arthritis in very early arthritis patients. This consistency supports DMARD prescription as a valid surrogate endpoint for chronic arthritis. Importantly, this surrogate is used in ongoing efforts to develop new diagnostic criteria for early RA.
19389230 Disease activity level, remission and response in established rheumatoid arthritis: perfor 2009 Apr 23 BACKGROUND: Most composite indices of disease activity and response criteria in RA have been validated and compared in clinical trials rather than routine care. We therefore wanted to compare the performance of the DAS28, SDAI and CDAI activity indices, their activity states, their response criteria, and also compare with the ACR response criteria in an observational clinical setting. METHODS: Agreement between the criteria sets was investigated using kappa statistics in a non-randomized cohort of 1789 RA patients from southern Sweden, starting their first course of anti-TNF-treatment. Mean disease duration was 12 years. Completer analysis was used. RESULTS: Agreement between high, moderate and low activity states was moderate or substantial, with kappa = 0.5 or better for all criteria. Agreement between SDAI and CDAI disease states was > 90% in these categories with kappa > 0.8. DAS28 original and modified cut point remission had good agreement (kappa = 0.91). Agreement between responses was substantial at the overall/ACR20 level (about 95%, kappa = 0.7 or better) for all criteria. By contrast, agreement was poor between moderate and high level responses. CONCLUSION: Disease activity states according to the various indices perform similarly and show substantial agreement at all levels except remission. Agreement between SDAI and CDAI states is excellent. Response criteria, applied at the individual patient level, are hard to interpret and show poor agreement, except at the lowest level of response. Thus, they should not be applied uncritically in clinical practice.
21428159 Laparoscopic aspiration cytology in rheumatoid ascites: a case report. 2010 Nov BACKGROUND: To the best of our knowledge, there are currently no recorded cytologic features of any effusion from rheumatoid peritonitis showing cytologic findings linked to rheumatoid pleural disease, although rheumatoid nodules have been described in the peritoneum. CASE: A 75-year-old man with longstanding, poorly controlled rheumatoid arthritis was seen in our hospital after a motor vehicle collision. Computed tomography showed free fluid in the abdominal cavity. Laparoscopic examination revealed a large amount of nonhemorrhagic ascitic fluid and no traumatic intraabdominal injuries. Abdominal and peritoneal surfaces appeared completely normal. The ascitic fluid was aspirated through the laparoscope and sent for cytologic examination. Cytospin preparations revealed histiocytes and loosely cohesive clusters of small cytologically bland epithelioid cells amid acute inflammatory cells and granular necrotic debris. Cell block material displayed transected fibroconnective tissue fragments lined by hyperplastic mesothelium with squamous metaplasia. Immunohistochemical studies revealed that the mesothelial cells were positive for calretinin, cytokeratin 5/6, and p63. CONCLUSION: The ascites was attributed to peritoneal disease from rheumatoid arthritis, based on the cytologic findings, immuno-profile, exclusion of other possible causes (i.e., cirrhosis, nephrotic syndrome, protein-losing enteropathy, or drugs), and patient's clinical setting.
21073447 Lack of association between ADIPOQ rs266729 and ADIPOQ rs1501299 polymorphisms and cardiov 2011 Jan To assess the potential association between ADIPOQ rs266729 and rs1501299 gene polymorphisms, either isolated or in combination, and cardiovascular disease in patients with rheumatoid arthritis (RA), 674 patients seen at the rheumatology outpatient clinics of Hospital Xeral-Calde, Lugo, and Hospital San Carlos, Madrid, Spain, were analyzed. Genotyping was performed using predesigned TaqMan assays (Applied Biosystems, Foster City, CA). Carotid intima-media thickness, flow-mediated endothelium-dependent and endothelium-independent post-nitroglycerin vasodilatation, which are used as surrogate markers of subclinical atherosclerosis, were measured in a subsample. No significant differences in the genotype, allele or allele combination frequencies of both polymorphisms were found between RA patients with or without cardiovascular events or subclinical atherosclerosis. Therefore, ADIPOQ rs266729 and rs1501299 polymorphisms do not seem to be associated with cardiovascular disease in RA.
19184028 The benefits of yoga for rheumatoid arthritis: results of a preliminary, structured 8-week 2009 Oct The aim of this study was to measure the effects of a bi-weekly Raj yoga program on rheumatoid arthritis (RA) disease activity. Subjects were recruited from among RA patients in Dubai, United Arab Emirates by email invitations of the RA database. Demographic data, disease activity indices, health assessment questionnaire (HAQ), and quality of life (QOL) by SF-36 were documented at enrollment and after completion of 12 sessions of Raj yoga. A total of 47 patients were enrolled: 26 yoga and 21 controls. Baseline demographics were similar in both groups. Patients who underwent yoga had statistically significant improvements in DAS28 and HAQ, but not QOL. Our pilot study of 12 sessions of yoga for RA was able to demonstrate statistically significant improvements in RA disease parameters. We believe that a longer duration of treatment could result in more significant improvements.
19247592 [Early arthritis: action desired - treatment required]. 2009 Rheumatoid Arthritis (RA) is the most prevalent inflammatory joint disease in adults and shows a destructive course in most cases. The outcome of the disease - functional decline and invalidity - necessitates an early therapy. Recent studies demonstrate that the initiation of the treatment with a disease modifying antirheumatic drug (DMARD) treatment within the first three months after the onset of symptoms is crucial for sustained improvement of prognosis as well as therapeutic success and outcome. In the early stage of the disease, the criteria for the classification of Rheumatoid Arthritis (RA) are frequently not met. Up to over 50% of the patients show an arthritis, which cannot be classified and therefore is seen as undifferentiated arthritis (UA). Early therapeutic intervention appears to prevent the chronification of the disease; thus an early and appropriate disease modifying therapy is mandatory. Age, gender, involvement of the hands, positive rheumatoid factor, as well as the detection of anti cyclic-citrullinated peptide antibodies (anti-CCP Ab) are predictors of the development of RA. Beside conventional X-rays, there are other imaging methods such as magnetic resonance tomography imaging, Power-Doppler or contrast medium enhanced sonography, which may enable the detection not only of synovitis but also of erosive lesions at very early stages. Those patients suffering from UA carry a high risk for the development of a destructive arthritis as seen in RA, and therefore should be treated with an adequate DMARD. In these cases methotrexate is still the drug of first choice.
19222864 Hypoxia. The role of hypoxia and HIF-dependent signalling events in rheumatoid arthritis. 2009 An adequate supply of oxygen and nutrients is essential for survival and metabolism of cells, and consequentially for normal homeostasis. Alterations in tissue oxygen tension have been postulated to contribute to a number of pathologies, including rheumatoid arthritis (RA), in which the characteristic synovial expansion is thought to outstrip the oxygen supply, leading to areas of synovial hypoxia and hypoperfusion. Indeed, the idea of a therapeutic modality aimed at 'starving' tissue of blood vessels was born from the concept that blood vessel formation (angiogenesis) is central to efficient delivery of oxygen to cells and tissues, and has underpinned the development of anti-angiogenic therapies for a range of cancers. An important and well characterized 'master regulator' of the adaptive response to alterations in oxygen tension is hypoxia-inducible factor (HIF), which is exquisitely sensitive to changes in oxygen tension. Activation of the HIF transcription factor signalling cascade leads to extensive changes in gene expression, which allow cells, tissues and organisms to adapt to reduced oxygenation. One of the best characterized hypoxia-responsive genes is the angiogenic stimulus vascular endothelial growth factor, expression of which is dramatically upregulated by hypoxia in many cells types, including RA synovial membrane cells. This leads to an apparent paradox, with the abundant synovial vasculature (which might be expected to restore oxygen levels to normal) occurring nonetheless together with regions of synovial hypoxia. It has been shown in a number of studies that vascular endothelial growth factor blockade is effective in animal models of arthritis; these findings suggest that hypoxia may activate the angiogenic cascade, thereby contributing to RA development. Recent data also suggest that, as well as activating angiogenesis, hypoxia may regulate many other features that are important in RA, such as cell trafficking and matrix degradation. An understanding of the biology of the HIF transcription family may eventually lead to the development of therapies that are aimed at interfering with this key signalling pathway, and hence to modulation of hypoxia-dependent pathologies such as RA.
19563633 Early and long-standing rheumatoid arthritis: distinct molecular signatures identified by 2009 INTRODUCTION: Rheumatoid arthritis (RA) is a heterogeneous disease and its underlying molecular mechanisms are still poorly understood. Because previous microarray studies have only focused on long-standing (LS) RA compared to osteoarthritis, we aimed to compare the molecular profiles of early and LS RA versus control synovia. METHODS: Synovial biopsies were obtained by arthroscopy from 15 patients (4 early untreated RA, 4 treated LS RA and 7 controls, who had traumatic or mechanical lesions). Extracted mRNAs were used for large-scale gene-expression profiling. The different gene-expression combinations identified by comparison of profiles of early, LS RA and healthy synovia were linked to the biological processes involved in each situation. RESULTS: Three combinations of 719, 116 and 52 transcripts discriminated, respectively, early from LS RA, and early or LS RA from healthy synovia. We identified several gene clusters and distinct molecular signatures specifically expressed during early or LS RA, thereby suggesting the involvement of different pathophysiological mechanisms during the course of RA. CONCLUSIONS: Early and LS RA have distinct molecular signatures with different biological processes participating at different times during the course of the disease. These results suggest that better knowledge of the main biological processes involved at a given RA stage might help to choose the most appropriate treatment.
19252818 Rheumatoid arthritis (RA)-specific autoantibodies in patients with interstitial lung disea 2009 May The purpose of this study was to identify rheumatoid arthritis (RA)-related autoantibodies in subjects with interstitial lung disease (ILD) and no articular findings of RA, supporting the hypothesis that RA-related autoimmunity may be generated in non-articular sites, such as the lung. This was a retrospective chart review utilizing clinic databases of patients with ILD to identify cases with lung disease, RA-related autoantibody positivity, and no clinical evidence of articular RA. Four patients with ILD, RF, and anti-CCP positivity and no articular findings of RA were identified. All four patients were male with a mean age at time of diagnosis of ILD of 70 years old. All had a history of smoking. Three patients died within 2 years of diagnosis of ILD and never developed articular symptoms consistent with RA; the final case met full criteria for articular RA several months after stopping immunosuppressive treatment for ILD. RF and anti-CCP can be present in smokers with ILD without clinical evidence of articular RA and in one case symptomatic ILD and autoantibody positivity preceded the development of articular RA. These findings suggest that RA-specific autoimmunity may be generated due to immunologic interactions in the lung and may be related to environmental factors such as smoking.
20735865 A personal journey from the joint to the heart. 2010 Predicting complications of diseases such as rheumatoid arthritis (RA) as well as the efficacy and toxicity of drugs used to treat the disease based on an understanding of genetic differences is leading to the development of highly individualized, personal medicine. The prevention of cardiovascular complications of RA has assumed greater importance as our ability to treat the underlying joint disease has improved and it may be possible to predict which patients with RA are at greatest risk of developing cardiovascular disease.
20739221 Rheumatoid arthritis progression mediated by activated synovial fibroblasts. 2010 Oct Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovial hyperplasia and progressive joint destruction. Rheumatoid arthritis synovial fibroblasts (RASFs) are leading cells in joint erosion and contribute actively to inflammation. RASFs show an activated phenotype that is independent of the inflammatory environment and requires the combination of several factors. Although new aspects regarding RASF activation via matrix degradation products, epigenetic modifications, inflammatory factors, Toll-like receptor (TLR) activation and others have recently been uncovered, the primary pathophysiological processes in early arthritis leading to permanent activation are mostly unknown. Here, we review new findings regarding RASF activation and their altered behavior that contribute to matrix destruction and inflammation as well as their potential to spread RA.
19858120 Arterial stiffness and cumulative inflammatory burden in rheumatoid arthritis: a dose-resp 2009 Dec OBJECTIVE: To quantify the relationship between arterial stiffness and cumulative inflammatory burden in patients with RA. METHODS: We recruited RA patients without overt arterial disease aged 40-65 years, attending hospital rheumatology outpatient clinics. Standardized research nurse assessment included blood pressure (BP), pulse wave analysis (PWA, SphygmoCor), BMI, fasting blood sample (lipids, glucose, RF and ESR), patient questionnaire (smoking, alcohol, diet, exercise, family history of premature coronary heart disease and Stanford HAQ), current medication and medical record review. Cumulative inflammatory burden was measured as ESR area-under-the-curve (ESR-years) extracted from medical records. Arterial stiffness was measured using PWA [aortic augmentation index (AIX@75)]. Multiple linear regression was used to adjust for age, sex and nine other cardiovascular risk factors. RESULTS: We recruited 114 RA patients (mean age 54 years, female 81%, current DMARD 90%, current NSAID 70%, ACR criteria 56%) comprising 1040 RA person-years. Cholesterol, glucose and BMI were similar in women and men. Women had a longer duration of arthritis (10 vs 7 years) and were more likely to be seropositive (85 vs 71%). BP, smoking and alcohol consumption were lower for women. On fully adjusted analysis, an increase of 100 ESR-years was associated with an increase in AIX@75 of 0.51 (95% CI 0.13, 0.88). On fully adjusted analysis restricted to women the increase was 0.43 (95% CI 0.01, 0.85). CONCLUSIONS: In RA patients free of overt arterial disease, a dose-response relationship exists between cumulative inflammatory burden and arterial stiffness. This relationship is independent of established CV risk factors.
20808171 Familial Mediterranean fever presenting as anti-cyclic citrullinated peptide antibody nega 2010 Sep A 64-year-old Egyptian man who resides in the United States presented to the rheumatology clinic with 6 months history of episodic recurrent pauci--arthritis along with constitutional symptoms. His Mediterranean ancestry, anti-cyclic citrullinated peptide negativity, and cyclical palindromic rheumatism prompted an investigation for familial Mediterranean fever gene mutation. He was found to have heterozygous 694I gene mutation during MEFV analysis. He also met Liveneh 1 major and 1 minor criteria for the diagnosis of familial Mediterranean fever.
21874999 [Cardiovascular diseases and rheumatoid arthritis]. 2010 Morbidity and mortality rates are higher in rheumatoid arthritis (RA) patients than in the general population. RA is associated with an increased risk of cardiovascular disease. All of the cardiac structures can be affected during the course of RA. Rheumatoid arthritis, per se, is a cardiovascular (CV) risk factor as arterial hypertension, dyslipidemia and diabetes etc. Although the increased CV risk is acknowledged, limited attention is paid to detecting and managing CV comorbid conditions. Early identification, adequate CV risk management and ongoing monitoring of risk factors are mandatory to reduce the CV risk. Also, adequate control of arthritis disease activity is necessary to lower CV risk.
19922016 The role of psychological distress and personality variables in the disablement process in 2009 Nov OBJECTIVE: To test whether psychological distress and personality variables mediate or moderate physical health-related quality of life (HRQOL) in rheumatoid arthritis (RA) patients. METHODS: In 168 RA patients the following self-report instruments were administered: the Health Assessment Questionnaire (HAQ), the General Health Questionnaire (GHQ), the Defence Style Questionnaire (DSQ), the Hostility and Direction of Hostility Questionnaire (HDHQ), and the Sense of Coherence (SOC) scale. A total of 152 patients with several rheumatological disorders [56 with systemic sclerosis (SSc), 56 with systemic lupus erythematosus (SLE) and 40 with Sjögren's syndrome (SS)] served as disease controls. The outcome measure was the physical scale of the World Health Organization Quality of Life Instrument, Short Form (WHOQOL-BREF). We used hierarchical regression to determine whether our data were consistent with the disablement process model. RESULTS: In RA patients, sense of coherence was associated with physical HRQOL but the relationship was mediated by psychological distress. Self-sacrificing defence style moderated the relationship between pain and physical HRQOL: pain was associated with impaired physical HRQOL only in patients with predominant self-sacrificing defence style. Although psychological distress and personality variables were also associated with physical HRQOL in the disease control group, the moderating effects of personality on physical HRQOL were unique to RA. Thus, in RA, psychological distress, functional disability, and the interaction term between pain and self-sacrificing defence style were independently associated with physical HRQOL. CONCLUSIONS: In RA patients, psychological distress mediated the association of personality variables with physical HRQOL but personality moderated the effects of pain on physical HRQOL and this could be relevant to psychological interventions.
18765428 Cellular characterisation of magnetic resonance imaging bone oedema in rheumatoid arthriti 2009 Feb OBJECTIVES: Magnetic resonance imaging (MRI) bone oedema is an important predictor of bone erosion in rheumatoid arthritis (RA). This study aimed to determine the cellular components of MRI bone oedema, and clarify the relationship between bone erosion and MRI bone oedema. METHODS: Twenty-eight bones from 11 patients with RA undergoing orthopaedic surgery were analysed by quantitative and semi-quantitative immunohistochemistry. Pre-operative contrast-enhanced MRI scans were analysed for bone oedema. RESULTS: The density of osteoclasts was higher in those samples with MRI bone oedema than those without MRI bone oedema (p = 0.01). Other cells identified within bone marrow included macrophages and plasma cells, and these were more numerous in samples with MRI bone oedema (p = 0.02 and 0.05 respectively). B cells were present in lower numbers, but B cell aggregates were identified in some samples with MRI bone oedema. There was a trend to increased RANKL expression in samples with MRI bone oedema (p = 0.09). Expression of RANKL correlated with the number of osteoclasts (r = 0.592, p = 0.004). CONCLUSIONS: The increased number of osteoclasts and RANKL expression in samples with MRI bone oedema supports the hypothesis that bone erosion in RA occurs through activation of local bone resorption mechanisms within subchondral bone as well as through synovial invasion into bone.