scholarly journals Investigation of Lake Hévíz Mineral Water Balneotherapy and Hévíz Mud Treatment in Murine Osteoarthritis and Rheumatoid Arthritis Models

2018 ◽  
Vol 2018 ◽  
pp. 1-15 ◽  
Author(s):  
V. Tékus ◽  
É. Borbély ◽  
T. Kiss ◽  
A. Perkecz ◽  
Á. Kemény ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Structural Damage ◽  
Thermal Water ◽  
Tap Water ◽  
Weight Bearing ◽  
Combined Treatment ◽  
Joint Damage ◽  
Bone Destruction ◽  
Mechanical Hyperalgesia ◽  
Anti Inflammatory

Arthritic diseases are the most frequent causes of chronic pain and disability. Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial inflammation and progressive structural joint damage. Osteoarthritis is a degenerative process of the articular cartilage associated with hypertrophic changes in the bone. The aim of the present study was to investigate the anti-inflammatory and analgesic effects of Hévíz thermal water and mud in monosodium iodoacetate- (MIA-) (25 mg/ml, 20 μl i.a.) induced osteoarthritis and Complete Freund’s adjuvant- (CFA-) (1 mg/ml, 50–50 μl s.c) induced rheumatoid arthritis murine models. The mechanonociceptive threshold of female NMRI mice (n=6– 8 mice/ group) was measured by aesthesiometry, and paw volume was monitored with plethysmometry, knee joint diameter with digital micrometer, and dynamic weight bearing on the hind limbs with a Bioseb instrument. Periarticular bone destruction was assessed by SkyScan 1176 in vivo micro-CT. Inflammatory cytokines were detected by ELISA in plasma samples. Treatments (30 min, every working day) with tap water, sand, and a combined therapy of tap water and sand served as controls. Hévíz medicinal water and combined treatment with water and mud significantly decreased the mechanical hyperalgesia and knee oedema in MIA-induced osteoarthritis model. However, balneotherapy did not influence mechanical hyperalgesia, weight bearing, or oedema formation induced by CFA. Neither medicinal water nor mud treatment ameliorated deep structural damage of the bones or the joints in the animal models. On the basis of the present findings, we conclude that balneotherapy is an effective complementary treatment to reduce the pain sensation and swelling in degenerative joint diseases such as osteoarthritis. Our experimental data are in agreement with the previous human studies that also confirmed antinociceptive and anti-inflammatory effects of thermal water and Hévíz mud treatments.

scholarly journals Zoledronic acid ameliorates the effects of secondary osteoporosis in rheumatoid arthritis patients

2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Jun Xie ◽  
Shaohua Li ◽  
Lianbo Xiao ◽  
Guilin Ouyang ◽  
Lin Zheng ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Zoledronic Acid ◽  
Fracture Risk ◽  
Disease Activity ◽  
Combined Treatment ◽  
Joint Damage ◽  
Bone Destruction ◽  
Secondary Osteoporosis ◽  
Therapeutic Effects ◽  
Clinical Trial Registry

Abstract Background Secondary osteoporosis may occur in patients with rheumatoid arthritis (RA), causing irreversible joint damage and disability. Bisphosphonates, the recently developed bone resorption inhibitors, have demonstrated significant therapeutic effects on senile and postmenopausal osteoporosis. This study evaluated the efficacy and safety of zoledronic acid (ZOL), with or without methotrexate (MTX), for the prevention and treatment of bone destruction in RA patients. Methods We recruited 66 RA patients with symptoms of secondary osteoporosis. They were randomized into three treatment groups—combined treatment with MTX and ZOL, ZOL monotherapy, or MTX monotherapy—in two consecutive 6-month periods. The participants were followed for 12 months. At the end of each treatment period, improvement in disease activity, bone destruction, and fracture risk were evaluated. Results Combined treatment with ZOL and MTX had significantly better clinical efficacy compared with either ZOL or MTX monotherapy (P < 0.05). The combination significantly improved the lumbar spine and hip BMD and reduced FRAX scores, suggesting that ZOL combined with MTX reduces bone loss and risk of hip fracture in RA patients with secondary osteoporosis. Conclusion ZOL has a synergistic effect when combined with MTX, inhibiting RA disease activity, reducing fracture risk, and improving quality of life in RA patients with secondary osteoporosis. Trial registration Chinese Clinical Trial Registry, ChiCTR1800019290. Registered 3 November 2018–Retrospective registered, http://www.chictr.org.cn/showproj.aspx?proj = 31758

scholarly journals Managing Osteoporosis and Joint Damage in Patients with Rheumatoid Arthritis: An Overview

2021 ◽  
Vol 10 (6) ◽  
pp. 1241
Author(s):  
Yoshiya Tanaka
Keyword(s):  
Rheumatoid Arthritis ◽  
Structural Damage ◽  
Kinase Inhibitors ◽  
Joint Destruction ◽  
Joint Damage ◽  
Nuclear Factor Κb ◽  
Cartilage Destruction ◽  
Janus Kinase ◽  
Systemic Autoimmune Disease ◽  
And Cartilage

In rheumatoid arthritis, a representative systemic autoimmune disease, immune abnormality and accompanying persistent synovitis cause bone and cartilage destruction and systemic osteoporosis. Biologics targeting tumor necrosis factor, which plays a central role in the inflammatory process, and Janus kinase inhibitors have been introduced in the treatment of rheumatoid arthritis, making clinical remission a realistic treatment goal. These drugs can prevent structural damage to bone and cartilage. In addition, osteoporosis, caused by factors such as menopause, aging, immobility, and glucocorticoid use, can be treated with bisphosphonates and the anti-receptor activator of the nuclear factor-κB ligand antibody. An imbalance in the immune system in rheumatoid arthritis induces an imbalance in bone metabolism. However, osteoporosis and bone and cartilage destruction occur through totally different mechanisms. Understanding the mechanisms underlying osteoporosis and joint destruction in rheumatoid arthritis leads to improved care and the development of new treatments.

scholarly journals Short-term changes on MRI predict long-term changes on radiography in rheumatoid arthritis: an analysis by an OMERACT Task Force of pooled data from four randomised controlled trials

2016 ◽  
Vol 76 (6) ◽  
pp. 992-997 ◽  
Author(s):  
Charles Peterfy ◽  
Vibeke Strand ◽  
Lu Tian ◽  
Mikkel Østergaard ◽  
Ying Lu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Structural Damage ◽  
Randomised Controlled Trials ◽  
Task Force ◽  
Joint Damage ◽  
Controlled Trials ◽  
X Rays ◽  
X Ray ◽  
Pooled Data ◽  
Randomised Controlled

ObjectiveIn rheumatoid arthritis (RA), MRI provides earlier detection of structural damage than radiography (X-ray) and more sensitive detection of intra-articular inflammation than clinical examination. This analysis was designed to evaluate the ability of early MRI findings to predict subsequent structural damage by X-ray.MethodsPooled data from four randomised controlled trials (RCTs) involving 1022 RA hands and wrists in early and established RA were analysed. X-rays were scored using van der Heijde-modified or Genant-modified Sharp methods. MRIs were scored using Outcome Measures in Rheumatology (OMERACT) RA MRI Score (RAMRIS). Data were analysed at the patient level using multivariable logistic regression and receiver operating characteristic curve analyses.ResultsProgression of MRI erosion scores at Weeks 12 and 24 predicted progression of X-ray erosions at Weeks 24 and 52, with areas under the curve (AUCs) of 0.64 and 0.74, respectively. 12-week and 24-week changes in MRI osteitis scores were similarly predictive of 24-week and 52-week X-ray erosion progressions; pooled AUCs were 0.78 and 0.77, respectively. MRI changes in synovitis at Weeks 12 and 24 also predicted progression of X-ray joint damage (erosion and joint-space narrowing) at Weeks 24 and 52 (AUCs=0.72 and 0.65, respectively).ConclusionsEarly changes in joint damage and inflammation detected with MRI predict changes in joint damage evident on subsequent X-rays. These findings support the use of MRI as a valid method for monitoring structural damage in short-duration RCTs.

scholarly journals Peptides Bearing Multiple Post-Translational Modifications as Antigenic Targets for Severe Rheumatoid Arthritis Patients

2021 ◽  
Vol 22 (24) ◽  
pp. 13290
Author(s):  
Cristina García-Moreno ◽  
María J. Gómara ◽  
Raúl Castellanos-Moreira ◽  
Raimon Sanmartí ◽  
Isabel Haro
Keyword(s):  
Rheumatoid Arthritis ◽  
Structural Damage ◽  
Serum Antibody ◽  
Joint Damage ◽  
Erosive Disease ◽  
Post Translational Modifications ◽  
Diagnosis And Prognosis ◽  
Modified Peptides ◽  
Chimeric Peptides

Rheumatoid arthritis (RA) is characterized by the presence of autoantibodies that are of paramount importance for the diagnosis and prognosis of the disease and have been implicated in its pathogenesis. Proteins resulting from post-translational modifications (PTMs) are capable of triggering autoimmune responses important for the development of RA. In this work, we investigate serum antibody reactivity in patients with an established RA against a panel of chimeric peptides derived from fibrin and filaggrin proteins and bearing from one to three PTMs (citrullination, carbamylation and acetylation) by home-designed ELISA tests (anti-AMPA autoantibodies). The role of anti-AMPAs as biomarkers linked to the presence of a more severe RA phenotype (erosive disease with radiological structural damage) and to the presence of interstitial lung disease (ILD), a severe extra-articular manifestation in RA patients entailing a high mortality, was also analyzed. In general, the association with the clinical phenotype of RA was confirmed with the different autoantibodies, and especially for IgA and IgM isotypes. The prevalence of severe joint damage was only statistically significant for the IgG isotype when working with the peptide bearing three PTMs. Furthermore, the median titers were significantly higher in patients with RA-ILD, a finding not observed for the IgG isotype when working with the single- and double-modified peptides.

scholarly journals An Anti-Inflammatory Composition of Boswellia serrata Resin Extracts Alleviates Pain and Protects Cartilage in Monoiodoacetate-Induced Osteoarthritis in Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Venkata Krishnaraju Alluri ◽  
Sreenath Kundimi ◽  
Krishanu Sengupta ◽  
Trimurtulu Golakoti ◽  
Eswar Kumar Kilari
Keyword(s):  
Articular Cartilage ◽  
Structural Damage ◽  
Weight Bearing ◽  
Prostaglandin E ◽  
Thermal Stimulus ◽  
Sprague Dawley ◽  
Boswellia Serrata ◽  
Anti Inflammatory ◽  
Safranin O ◽  
Unique Composition

The boswellic acids, the active compounds in Boswellia serrata gum resin extract, are potent anti-inflammatory agents and are specific nonredox inhibitors of 5-Lipoxygenase (5-LOX). Here, we present the anti-osteoarthritis (OA) efficacy of LI13019F1 (also known as Serratrin®), a unique composition containing the acidic and nonacidic fractions of B. serrata gum resin. This composition strongly inhibited 5-LOX activity with the half-maximal inhibitory concentration (IC50) of 43.35 ± 4.90 μg/mL. Also, LI13019F1 strongly inhibited the leukotriene B4 (IC50, 7.80 ± 2.40 μg/mL) and prostaglandin E2 (IC50, 6.19 ± 0.52 μg/mL) productions in human blood-derived cells. Besides, LI13019F1 reduced TNF-α production with the IC50 of 12.38 ± 0.423 μg/mL. On average, 1, 2.5, and 5 μg/mL doses of LI13019F1 protected 34.62, 47.66, and 62.29% SW1353 human chondrosarcoma cells from IL-1β induced SOX-9 depletion, respectively. Further, a 28-day preclinical proof-of-concept study evaluated the pain relief efficacy of LI13019F1 in monoiodoacetate- (MIA-) induced Sprague-Dawley rats. At the end of the study, 150 and 300 mg/kg doses of LI13019F1 supplemented rats showed significant improvements (55.17 ± 5.81 g (p<0.05), and 66.22 ± 6.30 g (p<0.05), respectively, vs. MIA: 31.22 ± 7.15 g) in body-weight-bearing capacities. Concurrently, LI13019F1-150 and LI13019F1-300 rats substantially (p<0.05) increased the threshold of pain sensitivity to pressure (26.98 ± 2.36 and 28.06 ± 2.72-gram force, respectively; vs. 18.63 ± 5.82 in MIA) and increased (p<0.05) the latent time to withdraw the paw after a thermal stimulus (23.61 ± 2.73 and 28.18 ± 1.90 sec, respectively; vs. 16.56 ± 1.22 sec. in MIA). Besides, the histological observations on Safranin-O green stained articular cartilage revealed that LI13019F1 also prevented the MIA-induced structural damage of the cartilage and reduced the loss of the extracellular matrix (ECM) components in the experimental rats. In conclusion, the present observations suggest that LI13019F1, a new composition of B. serrata gum resin extracts, reduces pain and protects articular cartilage from the damaging action of MIA in a rodent model.

Atomic Force Microscopy Study of the Anti-inflammatory Effects of Triptolide on Rheumatoid Arthritis Fibroblast-like Synoviocytes

2017 ◽  
Vol 23 (5) ◽  
pp. 1002-1012 ◽  
Author(s):  
Zhanhui Su ◽  
Han Sun ◽  
Man Ao ◽  
Chunying Zhao
Keyword(s):  
Rheumatoid Arthritis ◽  
Atomic Force Microscopy ◽  
Inflammatory Responses ◽  
Bone Destruction ◽  
Microscopy Study ◽  
Primary Role ◽  
Force Microscopy ◽  
Atomic Force ◽  
Anti Inflammatory ◽  
Fibroblast Like Synoviocytes

AbstractHigh-resolution atomic force microscopy (AFM) was used for the in situ evaluation of the anti-inflammatory effects of triptolide on rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) to understand the anti-RA effects of triptolide, based on the morphological and biophysical changes observed in RA-FLS. RA-FLS have been reported to play a primary role in inflammatory bone destruction during the development of RA and thus are regarded as an important target for RA treatment. Triptolide pretreatment significantly inhibited tumor necrosis factor-α-induced expression of the interleukin (IL)-1β, IL-6, and IL-8 genes in MH7A cells. Using AFM, we showed that triptolide-induced morphological damage in MH7A cells by inducing significant ultrastructure changes in the membrane, which were closely related to triptolide-induced apoptosis in MH7A cells. Using force measurements determined with AFM, triptolide was shown to increase the stiffness of MH7A cells. These findings not only revealed the strong anti-inflammatory effects of triptolide on RA-FLS, highlighting triptolide as a potential anti-RA agent, but also revealed the possible use of AFM for studying anti-inflammatory responses in RA-FLS, which we expect to be developed into a potential tool for anti-RA drug studies in RA-FLS.

scholarly journals Propionibacterium freudenreichii Inhibits RANKL-Induced Osteoclast Differentiation and Ameliorates Rheumatoid Arthritis in Collagen-Induced Arthritis Mice

2021 ◽  
Vol 10 (1) ◽  
pp. 48
Author(s):  
Jiah Yeom ◽  
Dong Joon Yim ◽  
Seongho Ma ◽  
Young-Hee Lim
Keyword(s):  
Rheumatoid Arthritis ◽  
Mouse Model ◽  
Bone Erosion ◽  
Osteoclast Differentiation ◽  
Joint Damage ◽  
Bone Destruction ◽  
In Vivo Studies ◽  
Propionibacterium Freudenreichii ◽  
Limited Information ◽  
Collagen Induced Arthritis

Osteoclast differentiation is crucial for bone absorption, and osteoclasts are involved in bone destruction in rheumatoid arthritis (RA). Dairy Propionibacterium freudenreichii is used as a cheese starter and possesses prebiotic and postbiotic properties. It is known to stimulate the growth of bifidobacteria and produces valuable metabolites, such as vitamin B12 and propionic acid. However, limited information is available on the beneficial effects of P. freudenreichii on human disease. Herein, we aimed to investigate the inhibitory effect of P. freudenreichii MJ2 (MJ2) isolated from raw milk on osteoclast differentiation and evaluate the improvement in RA. The murine macrophage cell line, RAW 264.7, and a collagen-induced arthritis (CIA) mouse model were used to perform in vitro and in vivo studies, respectively. Heat-killed P. freudenreichii MJ2 (hkMJ2)-treated cells significantly inhibited RANKL-induced osteoclast differentiation and TRAP activity. HkMJ2-treated cells exhibited significantly decreased expression of genes and proteins related to RANKL-induced osteoclast differentiation. MJ2 administration decreased the arthritic score in the CIA mouse model. Live and dead MJ2 inhibited bone loss and afforded protection against bone erosion and joint damage in CIA mice. MJ2 decreased the levels of collagen-specific antibodies and inflammatory cytokines and the expression of osteoclast differentiation-related genes and proteins in CIA mice. Interestingly, live and dead MJ2 showed similar RA improvement effects in CIA mice. In conclusion, P. freudenreichii MJ2 inhibited osteoclast differentiation by inhibiting the NF-κB signaling pathway and ameliorated CIA.

scholarly journals Continued inhibition of structural damage over 2 years in patients with rheumatoid arthritis treated with rituximab in combination with methotrexate

2010 ◽  
Vol 69 (6) ◽  
pp. 1158-1161 ◽  
Author(s):  
Stanley B Cohen ◽  
Edward Keystone ◽  
Mark C Genovese ◽  
Paul Emery ◽  
Charles Peterfy ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Structural Damage ◽  
Joint Space Narrowing ◽  
Joint Damage ◽  
Joint Space ◽  
Tnf Inhibitors ◽  
Inadequate Response ◽  
Intention To Treat ◽  
Damage Progression ◽  
Sustained Effects

BackgroundRituximab inhibited structural damage at 1 year in patients with rheumatoid arthritis (RA) who had had a previous inadequate response to tumour necrosis factor (TNF) inhibitors.ObjectiveTo assess structural damage progression through 2 years.MethodsIntention-to-treat patients with one post-baseline radiograph (rituximab n=281; placebo n=187) received background methotrexate (MTX) and were randomised to rituximab (2×1000 mg infusions, 2 weeks apart) or placebo; patients were eligible for rituximab re-treatment every 6 months. By week 104, 82% of the placebo population had received ≥1 dose of rituximab. Radiographic end points included the change in total Sharp score (TSS), erosion and joint space narrowing scores at week 104.ResultsAt week 104, significantly lower changes in TSS (1.14 vs 2.81; p<0.0001), erosion score (0.72 vs 1.80; p<0.0001) and joint space narrowing scores (0.42 vs 1.00; p<0.0009) were observed with rituximab plus MTX vs placebo plus MTX. Within the rituximab group, 87% who had no progression of joint damage at 1 year remained non-progressive at 2 years.ConclusionsRituximab plus MTX demonstrated significant and sustained effects on joint damage progression in patients with RA and a previously inadequate response to TNF inhibitors.

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