Browsing by keyword "Spondyloarthritis"
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Differential Effects of Inflammation on Bone and Response to Biologics in Rheumatoid Arthritis and SpondyloarthritisPURPOSE OF REVIEW: We review the pathways, cytokines, and concepts important to the pathogenesis of bone resorption and formation in rheumatoid arthritis (RA) and spondyloarthritis (SpA). RECENT FINDINGS: Research in bone biology has shed light on the pathogenesis of the joint destruction that occurs in RA and in peripheral SpA. However, understanding the mechanisms behind the bone formation seen in peripheral and axial SpA has been challenging. Mouse models have been used to gain an understanding of key signaling pathways, cytokines and cells regulating inflammation in these diseases. Biologic therapies directed against these targets have been developed to control both inflammation and effects on bone. Although biologic therapies improve joint inflammation in both RA and SpA, leading to a decrease in pain and improving quality of life for patients, the long-term effects of such therapies must also be evaluated by assessing their impact on structural progression. Inhibition of radiographic progression in both RA and peripheral SpA has been easier to demonstrate than in axial SpA. Here, we discuss the similarities and differences among biologic therapies as they pertain to radiographic progression.
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IL-17A deficiency promotes periosteal bone formation in a model of inflammatory arthritisBACKGROUND: Interleukin-17A (IL-17A) plays a pathogenic role in several rheumatic diseases including spondyloarthritis and, paradoxically, has been described to both promote and protect from bone formation. We therefore examined the effects of IL-17A on osteoblast differentiation in vitro and on periosteal bone formation in an in vivo model of inflammatory arthritis. METHODS: K/BxN serum transfer arthritis was induced in IL-17A-deficient and wild-type mice. Clinical and histologic inflammation was assessed and periosteal bone formation was quantitated. Murine calvarial osteoblasts were differentiated in the continuous presence of IL-17A with or without blockade of secreted frizzled related protein (sFRP)1 and effects on differentiation were determined by qRT-PCR and mineralization assays. The impact of IL-17A on expression of Wnt signaling pathway antagonists was also assessed by qRT-PCR. Finally, regulation of Dickkopf (DKK)1 expression in murine synovial fibroblasts was evaluated after treatment with IL-17A, TNF, or IL-17A plus TNF. RESULTS: IL-17A-deficient mice develop significantly more periosteal bone than wild-type mice at peak inflammation, despite comparable severity of inflammation and bone erosion. IL-17A inhibits calvarial osteoblast differentiation in vitro, inducing mRNA expression of the Wnt antagonist sFRP1 in osteoblasts, and suppressing sFRP3 expression, both potentially contributing to inhibition of osteoblast differentiation. Furthermore, a blocking antibody to sFRP1 reduced the inhibitory effect of IL-17A on differentiation. Although treatment with IL-17A suppresses DKK1 mRNA expression in osteoblasts, IL-17A plus TNF synergistically upregulate DKK1 mRNA expression in synovial fibroblasts. CONCLUSIONS: IL-17A may limit the extent of bone formation at inflamed periosteal sites in spondyloarthritis. IL-17A inhibits calvarial osteoblast differentiation, in part by regulating expression of Wnt signaling pathway components. These results demonstrate that additional studies focusing on the role of IL-17A in bone formation in spondyloarthritis are indicated.
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Mediators of inflammation and bone remodeling in rheumatic diseaseRemodeling of bone is a continuous process that occurs throughout life. Under normal physiologic conditions, bone-resorbing osteoclasts and bone-forming osteoblasts are tightly coupled and regulated to ensure proper balance, such that there is no net change in bone mass. However, inflammation perturbs normal bone homeostasis. The impact of inflammation on bone is dependent upon the anatomic site affected, cell types, factors and cytokines present in the local microenvironment, and local mechanical forces. Cytokines are central to the pathogenesis of inflammation-induced bone loss and contribute to the uncoupling of osteoclast-mediated bone resorption and osteoblast-mediated bone formation, thereby disrupting normal remodeling. In this review, we will discuss the effects of cytokines on bone in two settings, rheumatoid arthritis and spondyloarthritis, a disease category that includes ankylosing spondylitis, psoriatic arthritis, reactive arthritis, inflammatory bowel disease, and juvenile onset spondyloarthropathy. The outcome for bone in these disease settings is quite different, and an understanding of the pathogenic mechanisms leading to the net impact on bone has been essential in developing new therapeutic approaches to bone health in these diseases.
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Patient perspectives on health care provider practices leading to an axial spondyloarthritis diagnosis: an exploratory qualitative research studyBACKGROUND: The average time to a diagnosis for people with axial spondyloarthritis (axSpA) is 7-10 years. Delayed diagnosis may result in increased structural damage, worse physical function, and worse quality of life relative to patients with a timely axSpA diagnosis. Understanding patient experiences may provide insights for how to reduce diagnostic delays. OBJECTIVE: To provide foundational knowledge about patient experiences with healthcare providers leading to an axSpA diagnosis. METHODS: We conducted an exploratory qualitative research study with six focus groups interviews with participants recruited from three rheumatology clinics within the United States (MA (n = 3); CO (n = 2); PA (n = 1)) that included a total of 26 adults (10 females, 16 males) with rheumatologist confirmed diagnosis of axSpA in 2019. Focus groups were ~ 2 h, audio recorded, transcribed, and subject to dual coding. The codes reviewed were in relation to the patients' diagnostic experiences. RESULTS: Patients described frustrating and lengthy diagnostic journeys. They recognized that the causes of diagnostic delays in axSpA are multifactorial (e.g., no definitive diagnostic test, disease characteristics, lack of primary care provider's awareness about axSpA, trust). Patients described how doctors minimized or dismissed complaints about symptoms or told them that their issues were psychosomatic. Patients believed the healthcare system contributed to diagnostic delays (e.g., lack of time in clinical visits, difficulty accessing rheumatologists, health insurance challenges). Advice to physicians to reduce the diagnostic delay included allowing time for patients to give a complete picture of their illness experience, listening to, and believing patients, earlier referral to rheumatology, provision of HLA-B27 gene testing, and that physicians need to partner with their patients. CONCLUSIONS: Patients desire a definitive test that could be administered earlier in the course of axSpA. Until such a test is available, patients want clinicians who listen to, believe, and partner with them, and who will follow them until a diagnosis is reached. Educating primary care clinicians about guidelines and referral for diagnosis of axSpA could reduce diagnostic delay.
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Physical activity and attitudes and perceptions towards physical activity in patients with spondyloarthritis: A systematic reviewOBJECTIVE: To review systematically and synthesize qualitatively the literature about physical activity and perceptions and attitudes towards physical activity/exercise among patients with spondyloarthritis (SpA). METHODS: PubMed, CINAHL and Scopus and reference lists were searched for quantitative and qualitative studies reporting on beliefs towards exercise in patients with SpA. Searches were limited to studies published from January 2000 through December 2018. The PRISMA guidelines were followed. Systematic searches identified 128 publications which underwent a title, abstract, or full-text review. Studies were excluded if articles were not in English or did not include original data. We summarized the methodologic quality using modified criteria for quantitative and qualitative studies. RESULTS: Eight quantitative and three qualitative studies met eligibility criteria, with variable study quality. Based on self-reported data, 50% to 68% of patients with SpA met physical activity recommendations with walking, swimming/pool exercise, and cycling the most common forms reported. Intrinsic factors such as motivation and improvement in symptoms and health were commonly reported as facilitators associated with physical activity/exercise. Barriers included lack of time, fatigue, and symptoms such as pain. CONCLUSION: One third to one half of patients with SpA do not meet physical activity recommendations. Given the potential for regular physical activity to reduce symptom burden in this patient population and the recommendation for regular physical activity as part of the management of these patients, more rigorous studies of physical activity behaviors and attitudes will be useful to inform interventions and promote exercise among individuals with SpA.
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The term 'non-radiographic axial spondyloarthritis' is much more important to classify than to diagnose patients with axial spondyloarthritisThe term axial spondyloarthritis (axSpA) now is used frequently to describe patients with predominantly axial symptoms who fit into the spectrum of a well-recognised rheumatic disease that continues to be known as ankylosing spondylitis (AS). The 2009 Assessment of SpondyloArthritis international Society (ASAS) classification criteria, developed to identify patients with early or atypical disease which could not be classified by the 1984 modified New York (mNY) criteria for AS, have led to a differentiation between non-radiographic axial spondyloarthritis (nr-axSpA) and radiographic axSpA, which is largely synonymous with AS. The main reason to distinguish between these ends of the spectrum of axSpA was that tumor necrosis factor (TNF) inhibitors (TNFi) approved for AS could obtain additional labelling for nr-axSpA and be used to treat all patients manifesting clinical features of axSpA. These two terms are distinguished by the degree of 'radiographic sacroiliitis' assessed by conventional radiography, according to the 1984 mNY criteria for AS. Since this differentiation has been shown to be not very reliable, we argue that the terms nr-axSpA and AS should only be used for classification of patients with axSpA and not as separate diagnoses. Therefore, we propose that only the term axSpA be used to diagnose patients, unless there is a meaningful medical reason to differentiate nr-axSpA from AS. The available data justify performing randomised controlled trials designed to obtain regulatory approval for therapeutic agents in patients across the entire spectrum of axSpA.
