scholarly journals Dual Blockade of TNF and IL-17A Inhibits Inflammation and Structural Damage in a Rat Model of Spondyloarthritis

2022 ◽  
Vol 23 (2) ◽  
pp. 859
Author(s):  
Ihsan Hammoura ◽  
Renee H. Fiechter ◽  
Shaughn H. Bryant ◽  
Susan Westmoreland ◽  
Gillian Kingsbury ◽  
...  
Keyword(s):  
Bone Formation ◽  
Rat Model ◽  
Structural Damage ◽  
Structural Changes ◽  
Ct Imaging ◽  
Control Treatment ◽  
Micro Ct ◽  
New Bone Formation ◽  
Dual Blockade ◽  
Dual Inhibition

The tumor necrosis factor (TNF) and IL-23/IL-17 axes are the main therapeutic targets in spondyloarthritis. Despite the clinical efficacy of blocking either pathway, monotherapy does not induce remission in all patients and its effect on new bone formation remains unclear. We aimed to study the effect of TNF and IL-17A dual inhibition on clinical disease and structural damage using the HLA-B27/human β2-microglobulin transgenic rat model of SpA. Immunized rats were randomized according to arthritis severity, 1 week after arthritis incidence reached 50%, to be treated twice weekly for a period of 5 weeks with either a dual blockade therapy of an anti-TNF antibody and an anti-IL-17A antibody, a single therapy of either antibody, or PBS as vehicle control. Treatment-blinded observers assessed inflammation and structural damage clinically, histologically and by micro-CT imaging. Both single therapies as well as TNF and IL-17A dual blockade therapy reduced clinical spondylitis and peripheral arthritis effectively and similarly. Clinical improvement was confirmed for all treatments by a reduction of histological inflammation and pannus formation (p < 0.05) at the caudal spine. All treatments showed an improvement of structural changes at the axial and peripheral joints on micro-CT imaging, with a significant decrease for roughness (p < 0.05), which reflects both erosion and new bone formation, at the level of the caudal spine. The effect of dual blockade therapy on new bone formation was more prominent at the axial than the peripheral level. Collectively, our study showed that dual blockade therapy significantly reduces inflammation and structural changes, including new bone formation. However, we could not confirm a more pronounced effect of dual inhibition compared to single inhibition.

Significance of structural changes in the sacroiliac joints of patients with axial spondyloarthritis detected by MRI related to patients symptoms and functioning

2021 ◽  
pp. annrheumdis-2021-221406
Author(s):  
Juergen Braun ◽  
Uta Kiltz ◽  
Xenofon Baraliakos
Keyword(s):  
Bone Formation ◽  
Structural Damage ◽  
Structural Changes ◽  
Axial Spondyloarthritis ◽  
Conventional Radiography ◽  
Axial Skeleton ◽  
Interleukin 17 ◽  
New Bone Formation ◽  
Sacroiliac Joints ◽  
Magnetic Resonance Imaging Mri

Axial spondyloarthritis (axSpA) is a chronic inflammatory rheumatic disease that manifests primarily in the axial skeleton, initially mostly in the sacroiliac joints (SIJ), usually later spreading to the spine. The disease is characterised by inflammation and new bone formation which are mainly assessed by conventional radiography (CR) and magnetic resonance imaging (MRI). Tumour necrosis factor inhibitors (TNFi) and interleukin-17 antagonists have been shown to be efficacious and efficient in patients with axSpA. This treatment seems to also inhibit structural damage, for example, retard radiographic progression. Indeed, a reduction of new bone formation in the spine, as assessed by CR, has been reported to occur after at least 2 years of therapy with TNFi. Recently, a reduction of erosions and ankylosis in the SIJ has also been observed in axSpA patients treated with etanercept and filgotinib. In this narrative review, we discuss the limited significance of such findings.

scholarly journals AB1087 DETECTING AXIAL AND PERIPHERAL NEW BONE FORMATION IN SPONDYLOARTHRITIS PATIENTS USING [18F]FLUORIDE PET-CT IMAGING

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1832.2-1833
Author(s):  
J. De Jongh ◽  
R. Hemke ◽  
G. C. J. Zwezerijnen ◽  
M. Yaqub ◽  
I. Van der Horst-Bruinsma ◽  
...  
Keyword(s):  
Ankylosing Spondylitis ◽  
Bone Formation ◽  
Ct Imaging ◽  
Whole Body ◽  
Therapeutic Effects ◽  
New Bone Formation ◽  
Research Support ◽  
Patella Tendon ◽  
Pet Ct ◽  
18F Fluoride

Background:Bone formation in spondyloarthritis (SpA) is presumably related to local enthesitis/peri-articular inflammation and ultimately may lead to functional limitation (1,2). X-rays only allow long-term monitoring of bone formation (≥2 years) (3). Imaging techniques that can visualize bone formation at an early stage would therefore be valuable. Positron Emission Tomography (PET) using [18F]Fluoride can visualize and quantify (early changes in) bone formation at molecular level (4).Objectives:To investigate the feasibility of [18F]Fluoride to assess new bone formation at axial and peripheral enthesial sites in SpA patients.Methods:Thus far, 5 of the total of 15 patients with clinically active ankylosing spondylitis (AS) (according to modified New York criteria and BASDAI ≥4) and 8 of the 25 patients with active psoriatic arthritis (PsA) (according to CASPAR criteria and ≥1 clinically active enthesitis) were included. Of each patient, a whole body [18F]Fluoride PET-CT scan was performed. All scans were visually judged and scored dichotomously by one reader (blinded for clinical data) for PET-positive lesions in the spine, peripheral enthesis sites and joints. Low dose CT was used for anatomical reference.Results:The study is ongoing, with whole body [18F]Fluoride PET-CT scans available in five AS patients and eight PsA patients. In 4/5 AS scans, at least (≥1) PET positive lesions were found in the cervical, thoracic and/or lumbar vertebrae. These were mainly found in anterior corners of vertebrae and bridging syndesmophytes (Fig. 1A). In all eight PsA patients, at least 1 PET positive lesion was visualized, projected either at the site of a tendon attachment (fascia plantaris, achilles- and patella tendon (Fig 1B)) or peri-articularly (in the ankle or wrist).Fig 1.[18F]Fluoride uptake in the cervical, thoracic and lumbar spine in a clinically active AS patient (A) and in the patella tendon of the right knee in a clinically active PsA patient (B)Conclusion:[18F]Fluoride PET uptake, reflecting new bone formation, can be visualized at heterogeneously distributed enthesis and (peri-)articular sites in AS- and PsA patients. The technique therefore is sensitive to visualize new bone formation and may reflect local disease activity. Additional scans will be collected and analyzed quantitatively, also after anti-TNF or Secukinumab treatment, to further investigate the applicability of [18F]Fluoride PET for monitoring of therapeutic effects on bone formation in SpA.References: :[1]Maksymowych WP, Mallon C, Morrow S, Shojania K, Olszynski WP, Wong RL, et al. Development and validation of the Spondyloarthritis Research Consortium of Canada (SPARCC) Enthesitis Index. Ann Rheum Dis. 2009;68(6):948-53.[2]Rezvani A, Bodur H, Ataman S, Kaya T, Bugdayci DS, Demir SE, et al. Correlations among enthesitis, clinical, radiographic and quality of life parameters in patients with ankylosing spondylitis. Mod Rheumatol. 2014;24(4):651-6.[3]Rudwaleit M, Khan MA, Sieper J. The challenge of diagnosis and classification in early ankylosing spondylitis: do we need new criteria? Arthritis Rheum 2005;52:1000-8..[4]Bruijnen ST, Verweij NJF, van Duivenvoorde L, Bravenboer N, Baeten D, van Denderen JC, et al. [18F]Fluoride PET-CT imaging of bone formation in ankylosing spondylitis before and after 12 weeks of anti-TNF treatment. 2017.Acknowledgments:We thank EULAR Foreum, Pfizer and Novartis for financial support of this investigator initiated study.Disclosure of Interests:Jerney de Jongh: None declared, Robert Hemke: None declared, Gerben C.J. Zwezerijnen: None declared, Maqsood Yaqub: None declared, Irene van der Horst-Bruinsma Grant/research support from: AbbVie, Novartis, Eli Lilly, Bristol-Myers Squibb, MSD, Pfizer, UCB Pharma, Consultant of: AbbVie, Novartis, Eli Lilly, Bristol-Myers Squibb, MSD, Pfizer, UCB Pharma, Marleen G.H. van de Sande Grant/research support from: Novartis, Eli lily, UCB, Jansen, Consultant of: Abbvie, Novartis, Eli lily, MSD, Arno Van Kuijk: None declared, Irene Bultink: None declared, Lot Burgemeister: None declared, Nancy M.A. van Dillen: None declared, Alexandre Voskuyl: None declared, Conny J. van der Laken: None declared

Axial Spondyloarthritis and New Bone Formation

2021 ◽  
Vol 30 (04) ◽  
pp. 311-318
Author(s):  
Uta Syrbe
Keyword(s):  
Bone Formation ◽  
Structural Damage ◽  
Axial Spondyloarthritis ◽  
Clinical Symptoms ◽  
Research Work ◽  
New Bone Formation ◽  
Sacroiliac Joints ◽  
Spine Mobility ◽  
Vertebral Bodies ◽  
Inflammatory Changes

AbstractAxial spondyloarthritis is an inflammatory disease of the axial skeleton. Its pathogenesis is only partly understood. At the beginning, there are inflammatory changes in the sacroiliac joints which are followed by inflammation in vertebral bodies and in facet joints. Low back pain occurring in the morning hours is the dominant clinical symptom. In the early phase, inflammatory changes are detectably by MRI. Inflammation promotes a process of joint remodelling in the sacroiliac joints which leads to erosions, sclerosis and bony bridging, i. e. ankylosis, which are detectable by X-ray. In the spine, vertical osteophytes developing at sites of previous inflammation connect vertebral bodies as syndesmophytes. Additional ossification of longitudinal ligaments contributes to the so-called bamboo spine. Ossification of the spine promotes fixation of a severe kyphosis of the thoracic spine which strongly impairs spine mobility and quality of life. High disease activity seems a prominent risk factor for development of structural damage. However, although NSAIDs improve clinical symptoms, they do not reduce new bone formation. In contrast, TNFα and IL-17 inhibitors seem to retard new bone formation apart from their clinical efficacy. Research work of the last years identified immunological pathways of inflammation. However, the trigger and cellular components of the immune reaction in the bone marrow are still poorly defined. Osteoclasts are involved in the destruction of the subchondral bone, while osteoblasts facilitate new bone formation and cartilage ossification. This review gives an overview about diagnostics and therapy of axSpA and about risk factors for the development of structural damage. Concepts about the immune pathogenesis and joint remodeling in AS are given under recognition of genetic and histopathological studies.

Review – 3D Micro CT Imaging of Renal Micro-Structural Changes

2006 ◽  
Vol 103 (2) ◽  
pp. c66-c70 ◽  
Author(s):  
Mario Gössl ◽  
Michael D. Bentley ◽  
Lilach O. Lerman
Keyword(s):  
Structural Changes ◽  
Ct Imaging ◽  
Micro Ct

Pathology: bone

2016 ◽  
Author(s):  
Rik J. Lories ◽  
Georg Schett
Keyword(s):  
Bone Formation ◽  
Structural Damage ◽  
Axial Spondyloarthritis ◽  
Signalling Pathways ◽  
New Bone Formation ◽  
Different Types ◽  
Significant Burden ◽  
Current Therapies ◽  
Developmental Signalling ◽  
Biomechanical Factors

Axial spondyloarthritis is associated with different types of skeletal damage. Inflammation at the affected sites is linked with both loss of trabecular bone and new bone formation on the cortical side, potentially leading to joint or spine ankylosis. Both aspects of the disease can result in a significant burden for the patient. Bone loss is directly linked to proinflammatory cytokines and activation of osteoclasts. Control of inflammation is therefore the best strategy to prevent loss of bone. The nature of the new bone formation process is less defined. A prominent role for developmental signalling pathways has been proposed. Current therapies have limited or no impact on this process. However, emerging data suggest that early control of disease activity may be part of a window of opportunity to prevent structural damage, as biomechanical factors and instability following inflammation may also play a role.

scholarly journals Micro-CT Assessment of LED Irradiation on New Bone Formation in an Experimental Rat Calvaria Periosteal Elevation Model

2014 ◽  
Vol 35 (2) ◽  
pp. 151-157 ◽  
Author(s):  
Noboru Kuboyama ◽  
K. Bhawal Ujjal ◽  
Ryoichiro Uchida ◽  
Akira Kaneda ◽  
Yoshimitsu Abiko
Keyword(s):  
Bone Formation ◽  
Micro Ct ◽  
New Bone Formation ◽  
Rat Calvaria ◽  
Elevation Model ◽  
Led Irradiation

STAT3 phosphorylation inhibition for treating inflammation and new bone formation in ankylosing spondylitis

Rheumatology ◽  
2020 ◽  
Author(s):  
Sungsin Jo ◽  
Eun Jeong Won ◽  
Moon-Ju Kim ◽  
Yu Jeong Lee ◽  
So-Hee Jin ◽  
...  
Keyword(s):  
Bone Formation ◽  
Chronic Inflammation ◽  
Mononuclear Cells ◽  
Kinase Inhibitor ◽  
Janus Kinase ◽  
Micro Ct ◽  
New Bone Formation ◽  
Osteoprogenitor Cells ◽  
Suppression Effect ◽  
Stat3 Phosphorylation

Abstract Objective AS is a rheumatic disease characterized by chronic inflammation and bony ankylosis. This study was to evaluate whether a signal transducer and activator of transcription 3 phosphorylation inhibitor (stat3-p Inh) could treat both chronic inflammation and bone formation in AS. Methods Primary AS osteoprogenitor cells and spinal entheseal cells were examined for osteogenic differentiation. SF mononuclear cells (SFMCs) and lamina propria mononuclear cells (LPMCs) were obtained from AS patients. Inflammatory cytokine-producing cells were analysed using flow cytometry and ELISA. Female SKG mice were treated with stat3-p Inh, IL-17A blocker or vehicle. Inflammation and new bone formation were evaluated using immunohistochemistry, PET and micro-CT. Results In the SKG mouse model, stat3-p Inh significantly suppressed arthritis, enthesitis, spondylitis and ileitis. In experiments culturing SFMCs and LPMCs, the frequencies of IFN-γ-, IL-17A- and TNF-α-producing cells were significantly decreased after stat3-p Inh treatment. When comparing current treatments for AS, stat3-p Inh showed a comparable suppression effect on osteogenesis to Janus kinase inhibitor or IL-17A blocker in AS-osteoprogenitor cells. Stat3-p Inh suppressed differentiation and mineralization of AS-osteoprogenitor cells and entheseal cells toward osteoblasts. Micro-CT analysis of hind paws revealed less new bone formation in stat3-p Inh-treated mice than vehicle-treated mice (P = 0.005). Hind paw and spinal new bone formation were similar between stat3-p Inh- and anti-IL-17A-treated SKG mice (P = 0.874 and P = 0.117, respectively). Conclusion Stat-3p inhibition is a promising treatment for both inflammation and new bone formation in AS.

Micro-CT Analysis of New Bone Formation Around Implant with Electrochemically Deposited Apatite

2003 ◽  
Vol 240-242 ◽  
pp. 611-614 ◽  
Author(s):  
Seiji Ban ◽  
Norihiro Arimoto ◽  
Shozo Tsuruta ◽  
Hiroyuki Arikawa ◽  
Takahito Kanie ◽  
...  
Keyword(s):  
Bone Formation ◽  
Micro Ct ◽  
New Bone Formation ◽  
Electrochemically Deposited ◽  
Ct Analysis

scholarly journals Secukinumab in axial spondyloarthritis: a narrative review of clinical evidence

2021 ◽  
Vol 13 ◽  
pp. 1759720X2110418
Author(s):  
Jürgen Braun ◽  
Uta Kiltz ◽  
Björn Bühring ◽  
Xenofon Baraliakos
Keyword(s):  
Ankylosing Spondylitis ◽  
Bone Formation ◽  
Structural Damage ◽  
Axial Spondyloarthritis ◽  
Human Leukocyte ◽  
Signs And Symptoms ◽  
Axial Skeleton ◽  
Narrative Review ◽  
The European Union ◽  
New Bone Formation

Axial spondyloarthritis (axSpA) is a chronic inflammatory rheumatic disease characterized by inflammation and new bone formation in the axial skeleton. AxSpA is considered a spectrum of disease that includes two subtypes identified by the Assessment in SpondyloArthritis International Society classification criteria, namely, radiographic (r-axSpA usually referred to as ankylosing spondylitis) and non-radiographic axSpA (nr-axSpA). Although the burden of disease appears similar between the two classified subtypes, the degree of inflammation, as assessed by magnetic resonance imaging and C-reactive protein, and the degree of new bone formation are significantly higher in r-axSpA than in nr-axSpA. Nevertheless, axSpA is considered one disease with different courses. International guidelines for the management of axSpA have outlined treatment goals focused on control of signs and symptoms, inflammation, prevention of progressive structural damage, preservation of physical function, normalization of social participation and improvement of quality of life. The pathogenesis of axSpA has not been completely elucidated to date. A strong link between human leukocyte antigen B27 and axSpA, however, has been identified, and the success of anti-tumour necrosis factor and anti-interleukin (IL)-17A therapy has highlighted some of the key pro-inflammatory cytokines involved. The anti-IL-17A monoclonal antibody secukinumab is approved for the treatment of ankylosing spondylitis and nr-axSpA in the European Union and United States. In this narrative review, we discuss data for secukinumab in axSpA from randomized controlled trials, including MEASURE trials in AS and PREVENT in nr-axSpA, and real-world evidence.

scholarly journals Contrast Enhanced X-Ray Computed Tomography Imaging of Amyloid Plaques in Alzheimer Disease Rat Model on Lab Based Micro CT System

2020 ◽  
Author(s):  
Michaela Kavkova ◽  
Tomas Zikmund ◽  
Annu Kala ◽  
Jakub Salplachta ◽  
Stephanie Proskauer Pena ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Alzheimer’S Disease ◽  
Spatial Distribution ◽  
Brain Tissue ◽  
Rat Model ◽  
Amyloid Plaques ◽  
Ct Imaging ◽  
Micro Ct ◽  
X Ray ◽  
Contrast Enhanced

Abstract Amyloid plaques are small (~50 μm), highly-dense aggregates of amyloid beta (Aβ) protein in brain tissue, supposed to play a key role in pathogenesis of Alzheimer’s disease (AD). Plaques´ in vivo detection, spatial distribution and quantitative characterization could be an essential marker in diagnostics and evaluation of AD progress. However, current imaging methods in clinics possess substantial limits in sensitivity towards Aβ plaques to play a considerable role in AD screening. Contrast enhanced X-ray micro computed tomography (micro CT) is an emerging highly sensitive imaging technique capable of high resolution visualization of rodent brain. In this study we show the absorption based contrast enhanced X-ray micro CT imaging is viable method for detection and 3D analysis of Aβ plaques in transgenic rodent models of Alzheimer’s disease. Using iodine contrasted brain tissue isolated from the Tg-F344-AD rat model we show the micro CT imaging is capable of precise imaging of Aβ plaques, making possible to further analyze various aspects of their 3D spatial distribution and other properties.

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