Structural Damage In Rheumatoid Arthritis Research Articles

Structural damage in rheumatoid arthritis assessed by musculoskeletal ultrasound: A systematic literature review by the Structural Joint Damage Task Force of the OMERACT Ultrasound Working Group

ObjectivesTo identify and synthesize the evidence for the use and measurement properties of musculoskeletal ultrasound in assessing structural joint damage in patients with rheumatoid arthritis (RA). MethodsA systematic literature search (SLR) of the PubMed, Embase and Cochrane Library was performed. Original articles were included published in English reporting on ultrasound of bone erosion, cartilage damage and the measurement properties of ultrasound according to the OMERACT filter 2.1. ResultsOf the 1.495 identified articles 149 were included in the final review, most of which reported on cross-sectional studies and used the OMERACT definitions for ultrasonographic pathology. Among these, bone erosions were assessed in 139 (93.3%), cartilage damage in 24 (16.1%), enthesophytes in 8 (5.4%), osteophytes in 15 (10.1%) and malalignment and ankylosis in a single (0.9%) study, respectively. Most studies (126/149, 84.6%) assessed the joints of the hands. The overwhelming majority of studies (127/149, 85.2%) assessed structural joint damage bilaterally. Validity, reliability and responsiveness were assessed in 21 (14.1%), 34 (22.8%) and 17 (11.4%) studies, respectively. ConclusionWhile the results of this SLR suggest that ultrasound is a sensitive, reliable and feasible tool to detect damage in RA, they also highlight the need for further research and validation. Findings of this SLR will inform the next steps of the OMERACT Ultrasound Working Group in developing an ultrasound score for assessing structural joint damage in patients with RA.

Bisphosphonates in inflammatory rheumatic diseases.

The main well recognized action of bisphosphonates (BPs) is their antiresorptive capacity, making them first-line drugs in the treatment of osteoporosis and other metabolic bone diseases. In this review we have compiled other possible actions of BPs, particularly in the areas of immunomodulation, anti-inflammatory capacity and in the prevention of structural joint damage in inflammatory rheumatic diseases. The immunomodulatory capacity of BPs has been focused on the mechanisms involved in the acute-phase response associated with the administration of nitrogen containing BPs (N-BPs), with the stimulus of pro-inflammatory cytokines, through the mevalonate pathway, activation of T-cells and the decrease in the cytotoxic T-lymphocyte antigen-4 (CTLA-4). In relation to their anti-inflammatory capacity, special attention has been given to their effect on preventing structural damage in inflammatory joint diseases and on the differential immune response in bone lesions of the most common and representative inflammatory rheumatic diseases, i.e. rheumatoid arthritis and spondyloarthropathies. The present data indicate that more studies are needed to improve the knowledge on the effect of BPs on inflammatory-mediated diseases and particularly on the prevention and/or treatment of the structural damage in these disorders, since these agents could be a potential useful concomitant therapy.

The sonographic identification of cortical bone interruptions in rheumatoid arthritis: a morphological approach.

Bone erosions are the hallmark of structural damage in rheumatoid arthritis (RA). Among imaging techniques, ultrasonography (US) has emerged as an accurate, reliable, repeatable, low-cost and non-invasive imaging modality to detect erosive changes in RA. However, small interruptions of the cortical bone detectable by last generation US equipment do not necessarily represent bone erosions. According to the available data, in addition to cortical bone interruption itself, only a few morphological US findings have been proposed to define RA bone erosions. However, other additional features may be considered to facilitate the interpretation of US cortical bone interruptions in RA. These could be summarised using the following four domains: size, site, shape and scenery. This hypothesis article provides a critical literature review of US features characteristic of RA bone erosions and pictorial evidence supporting the potential role of a morphological analysis in the US identification of bone erosions in RA patients.Plain language summary The ultrasonographic morphology of cortical interruptions is helpful for the identification of bone erosions in rheumatoid arthritis: the “four Ss” approach Bone erosions are characteristic features of rheumatoid arthritis. They are associated with a more aggressive disease and with irreversible physical disability. In recent years, ultrasonography has emerged as an accurate and reliable technique for the detection of bone erosions, that appear as interruptions of the cortical bone with variable size. However, cortical bone interruptions do not necessarily represent bone erosions. Since bone erosions represent the earliest evidence of the destructive behaviour of RA, their identification is crucial.Besides the cortical interruption itself, only a few morphological ultrasonographic features were proposed to characterise bone erosions in rheumatoid arthritis.We believe that a morphological approach, including size, site, shape and scenery, may be considered to facilitate the interpretation of ultrasonographic cortical bone interruptions in rheumatoid arthritis.In this hypothesis article we carried out a critical review of the scientific literature and provided extensive pictorial evidence of the ultrasonographic spectrum of cortical interruptions supporting the potential role of considering the “four Ss” for the ultrasonographic identification of bone erosions in rheumatoid arthritis.

Inflammatory anemia may be an indicator for predicting disease activity and structural damage in Chinese patients with rheumatoid arthritis.

This study aimed to investigate the relationship of serum hemoglobin (HB) level with disease activity and structural damage in Chinese patients with rheumatoid arthritis (RA). A total of 890 RA patients and 890 normal subjects were enrolled in the case-control study. A HB threshold of< 110g/L (women) and < 120g/L (men) was used to determine anemia. All the patients were divided into three groups: non-anemia group (HB ≥ 120g/L (male) or 110g/L (female)), mild anemia group ((90g/L < HB < lower limit of normal), and medium to severe anemia group (HB ≤ 90g/L). Serum HB level and anemia prevalence between RA patients and normal subjects were compared. Associations of HB level with disease activity, structural damage, and function of joint in different groups were also investigated. The average of HB level in RA was (109.08 ± 17.96)g/l, which was lower than that in controls (136.75 ± 14.57)g/l (P < 0.001). Anemia was observed in 47% of the RA patients, while prevalence of anemia in control group was only 4.4%. In RA group, percentages of non-anemia, mild anemia, and medium to severe anemia were 47%, 38%, and 15%. Compared with non-anemia RA patients, RA patients with anemia had higher disease activity, severer structural damage and worse function of joint (P < 0.001). With the increase of anemia, the disease activity, structural damage, and dysfunction of joints increased significantly (P < 0.05-0.001). Linear regression analysis showed that HB level was negatively correlated with disease activity parameters, degree of joint destruction, and function (P < 0.05-0.001). Logistic regression indicated that serum HB level was protective factors for disease activity and structural damage in RA (P < 0.001). HB level was significantly related to disease activity and structural damage in RA patients.Key Points• Inflammatory anemia was popular (about a half) in patients with RA.• HB level was related to disease activity and structural damage in RA patients.

Estimation of drug effect in radiographic progression for rheumatoid arthritis and psoriatic arthritis.

To demonstrate the treatment effect on structural damage in rheumatoid arthritis (RA) and psoriatic arthritis (PsA), radiographic images of hands and feet are scored according to Sharp scoring systems in randomized clinical trials. However, the quantification of such an effect is challenging because the overall mean progression is lack of clinical interpretation. This article attempts to shed a light on the statistical challenges resulted from its scoring methods and heterogeneity of the study population and proposes a mixture distribution model approach to fit radiographic progression data. With such a model, the drug effect is fully captured by the mean progression of those patients who would progress in the study period under the control treatment. The resulting regression model also lends a tool in examining prognostic factors for radiographic progression. Simulations have been carried out to evaluate the precision of the parameter estimation procedure. Using the data examples from RA and PsA, we will show that the mixture distribution approach provides a better goodness of fit and leads to a casual inference of the study drug, hence a clinically meaningful interpretation.

Validity of the rheumatoid arthritis MRI score applied to the forefeet using the OMERACT filter: a systematic literature review

ObjectiveMRI depicts inflammation and structural damage in rheumatoid arthritis (RA). The validity of MRI-scoring of wrist-joints and metacarpophalangeal-joints according to the RA MRI score(RAMRIS) has been demonstrated. The Outcomes in...

Immune-bone interplay in the structural damage in rheumatoid arthritis.

The immune and bone systems maintain homeostasis by interacting closely with each other. Rheumatoid arthritis is a pathological consequence of their interplay, as activated T cell immune responses result in osteoclast-mediated bone erosion. An imbalance between forkhead box protein 3 (Foxp3)+ regulatory T (Treg ) cells and T helper type 17 (Th17) cells is often linked with autoimmune diseases, including arthritis. Th17 cells contribute to the bone destruction in arthritis by up-regulating receptor activator of nuclear factor kappa-Β ligand (RANKL) on synovial fibroblasts as well as inducing local inflammation. Studies on the origin of Th17 cells in inflammation have shed light on the pathogenic conversion of Foxp3+ T cells. Th17 cells converted from Foxp3+ T cells (exFoxp3 Th17 cells) comprise the most potent osteoclastogenic T cell subset in inflammatory bone loss. It has been suggested that osteoclastogenic T cells may have developed originally to stop local infection in periodontitis by inducing tooth loss. In addition, Th17 cells also contribute to the pathogenesis of arthritis by modulating antibody function. Antibodies and immune complexes have attracted considerable attention for their direct role in osteoclastogenesis, and a specific T cell subset in joints was shown to be involved in B cell antibody production. Here we summarize the recent advances in our understanding of the immune-bone interplay in the context of the bone destruction in arthritis.

Composite assessment of power Doppler ultrasonography and MRI in rheumatoid arthritis: a pilot study of predictive value in radiographic progression after one year.

Power Doppler ultrasonography (PDUS) and MRI are independently useful to predict structural damage in patients with rheumatoid arthritis (RA). We hypothesize that there is a complementary relationship between these modalities. The aim of this study is, therefore, to investigate the usefulness of the predictive value of composite assessment of PDUS and contrast-enhanced MRI in radiographic outcomes in patients with RA. 20 patients (17 females and 3 males) with RA on disease-modifying antirheumatic drugs underwent PDUS and MRI of both hands at baseline. Radiography of the bilateral hands was performed at baseline and at 1 year. Articular synovitis on PDUS was evaluated according to quantitative measurement. Synovitis, bone marrow edema and bone erosion were scored according to the RA MRI scoring method. The changes of joint space narrowing and bone erosion on radiograph were assessed by the Sharp/van der Heijde method. We applied t-statistics to combine the assessment of quantitative PDUS with semiquantitative MRI. Structural damage progression for radiography was not correlated with any evaluations for MRI, while it showed significant correlation with synovitis on PDUS (rs = 0.597, p = 0.005). The composite assessment of both modalities (synovitis for PDUS and bone marrow edema for MRI) was correlated with structural damage progression on radiograph (rs = 0.792, p < 0.0001). Composite assessment of PDUS and MRI may have a stronger predictive value in radiographic progression than PDUS or MRI alone in RA. Advances in knowledge: Composite assessment of PDUS and MRI may be an effective predictor of structural damage in RA.

A cross sectional study of bone and cartilage biomarkers: correlation with structural damage in rheumatoid arthritis

ABSTRACTThe aim of our study was to assess the relationship between bone and cartilage remodeling biomarkers and joint damage in Rheumatoid Arthritis (RA), and to detect whether they have the capacity to predict the progression of joint disease assessment by computed tomography (CT) erosion score. We analyzed 65 female patients with established RA in our Rheumatology Department. Serum levels of bone and cartilage markers were measured: osteocalcin (OC), N-propeptide of type I collagen (PINP), collagen type I and II, C-telopeptide (CTX I, CTX-II) and cartilage oligomeric matrix protein (COMP). Radiography of both wrist and MCP joints were available. Two expert-readers independently scored articular damage and progression using the High-resolution low dose CT scan in a blinded fashion. 65 female patients with established RA with a median age of 44 years were included. The median disease-duration was two years and the median (Disease activity score) DAS 28 score at 4.46 [2.65–7.36]. The percentage of patient with low disease activity was 13.8%, while 55.4 and 30.8% for those with moderate and high disease activity respectively. The resorption bone markers were high in active versus non-active RA. Wrist and MCP erosion scores were also associated with RA activity. Our study shows that biomarkers of bone and cartilage collagen breakdown were related to specific joint erosion in RA and could predict subsequent radiographic damage in RA. Further larger scale longitudinal studies maybe needed to confirm our data.

Cellular and molecular pathways of structural damage in rheumatoid arthritis.

Structural damage of cartilage and bone tissue is a hallmark of rheumatoid arthritis (RA). The resulting joint destruction constitutes one of the major disease consequences for patients and creates a significant burden for the society. The main cells executing bone and cartilage degradation are osteoclasts and fibroblast-like synoviocytes, respectively. The function of both cell types is heavily influenced by the immune system. In the last decades, research has identified several mediators of structural damage, ranging from infiltrating immune cells and inflammatory cytokines to autoantibodies. These factors result in an inflammatory milieu in the affected joints which leads to an increased development and function of osteoclasts and the transformation of fibroblast-like synoviocytes towards a highly migratory and destructive phenotype. In addition, repair mechanisms mediated by osteoblasts and chondrocytes are strongly impaired by the presence of pro-inflammatory cytokines. This article will review the current knowledge on the mechanisms of joint inflammation and the destruction of bone and cartilage.

Predictive value of tender joints compared to synovitis for structural damage in rheumatoid arthritis

ObjectiveTo evaluate the predictive value of tender joints compared to synovitis for structural damage in rheumatoid arthritis (RA).MethodsA post hoc analysis was performed on a prospective 2-year study of 59...

Calcium channels: the potential therapeutic targets for inflammatory bone destruction of rheumatoid arthritis.

Inflammatory bone resorption causes progressive joint destruction which ultimately leads to functional disability in rheumatoid arthritis (RA). The primary cell responsible for bone resorption is the osteoclast, which means it is a potential therapeutic target against bone destruction. In fact, experimental and clinical findings suggest that blockade of osteoclast differentiation and function is highly effective in inhibiting bone destruction in RA. In this report, we show several lines of experimental evidence which suggest that a variety of Ca(2+) channels are essential in osteoclast differentiation and function, and present a hypothesis that modulation of Ca(2+) channels is a highly effective therapeutic strategy in preventing osteoclast-induced structural damage in RA.

The Role of Power Doppler Ultrasonography as Disease Activity Marker in Rheumatoid Arthritis.

Structural damage in rheumatoid arthritis (RA) occurs early if inflammation is not treated promptly. Treatment targeted to reduce inflammation, in particular, that of synovial inflammation in the joints (synovitis), has been recommended as standard treat-to-target recommendations by rheumatologists. The goal is to achieve disease remission (i.e., no disease activity). Several accepted remission criteria have not always equated to the complete absence of true inflammation. Over the last decade, musculoskeletal ultrasonography has been demonstrated to detect subclinical synovitis not appreciated by routine clinical or laboratory assessments, with the Power Doppler modality allowing clinicians to more readily appreciate true inflammation. Thus, targeting therapy to Power Doppler activity may provide superior outcomes compared with treating to clinical targets alone, making it an attractive marker of disease activity in RA. However, more validation on its true benefits such as its benefits to patients in regard to patient related outcomes and issues with standardized training in acquisition and interpretation of power Doppler findings are required.

THU0254 Residual Inflammatory Activity Assessed by A Multi-Biomarker Disease Activity Blood Test is Linked to Structural Damage in RA Patients in Low Disease Activity/Remission and Normal C-Reactive Protein Level

BackgroundThe autoantibody positive (AAB+) subset of rheumatoid arthritis (RA) patients is prone to develop bone damage. Since the extent of bone erosion in AAB+ RA shows substantial variation, we hypothesized...

FRI0349 Exploring Symptom Duration, Auto Antibodies and Inflammation in Order to Explain the Predictive Value of Baseline Erosions for Future Structural Damage in Rheumatoid Arthritis

BackgroundBaseline erosions are characteristic for Rheumatoid Arthritis (RA) and predictive for the severity of structural damage during the disease. The mechanisms leading to baseline erosions being a strong predictor for...

AB0390 Serum RANKL Activity is Suppressed by TNF Alpha Inhibition but not with MTX Alone

BackgroundBone is, together with cartilage a central target of rheumatoid arthritis (RA). Chronic synovitis attacks the juxtaarticular bone, where it causes bone erosions. Formation of bone erosions is a consequence...

AB1000 Assessing the Impact of Subcutaneous Abatacept in Inhibiting Structural Damage in Rheumatoid Arthritis by Low Field Magnetic Resonance Imaging and X-Ray

BackgroundRheumatoid arthritis (RA) treatment has shifted from reducing symptoms to earlier inhibition of disease progression, thus preventing irreversible structural damage and disability. Detection of synovitis (SYN), osteitis (OST), and erosions...

AB0283 Articular Pain is Correlated with Ultrasound Power Doppler Findings?

BackgroundThe presence of power Doppler (PD) gives relevant information about the inflammatory status of the synovial tissue, but there is no evidence if it is correlated with pain symptom of...

Whole-body MRI assessment of disease activity and structural damage in rheumatoid arthritis: first step towards an MRI joint count

The aim of this study was to investigate the ability of whole-body MRI (WBMRI) to visualize inflammation [synovitis, bone marrow oedema (BME) and enthesitis] and structural damage in patients with RA. The 3T WBMR images were acquired in a head-to-toe scan in 20 patients with RA and at least one swollen or tender joint. Short Tau Inversion Recovery and pre- and post-contrast T1-weighted images were evaluated for readability and the presence/absence of inflammation (synovitis, BME and enthesitis) and structural damage (erosions and fat infiltrations) in 76 peripheral joints, 30 entheseal sites and in the spine. The readability was >70% for all individual joints, except for the most peripheral joints of the hands and feet. Synovitis was most frequent in the wrist, first tarsometatarsal, first CMC joints and glenohumeral joints (67-61%); BME in the wrist, CMC, acromioclavicular and glenohumeral joints (45-35%) and erosions in the wrist, MTP and CMC joints (19-16%). Enthesitis at ≥ 1 site was registered in 16 patients. BME was frequently seen in the cervical (20%) but not the thoracic and lumbar spine, while fat infiltrations and erosions were rare. The intrareader agreement was high (85-100%) for all pathologies. The agreement between WBMRI and clinical findings was low. Peripheral and axial inflammation and structural damage at joints and entheses was frequently identified by WBMRI, and more frequently than by clinical examination. WBMRI is a promising tool for evaluation of the total inflammatory load of inflammation (an MRI joint count) and structural damage in RA patients.

THU0143 Performance of Prediction Matrices for Rapid Radiologic Progression in Daily Practice

BackgroundRapid radiologic progression (RRP) is an important radiologic hallmark for structural damage in rheumatoid arthritis (RA) patients. For this purpose, various prediction matrices to detect risk on RRP were developed....