scholarly journals Iguratimod, A Synthetic Disease Modifying Anti- Rheumatic Drug (Sdmard), and Various Dmards Suppress Joint Destruction. The Pathophysiological Mechanisms of the Inhibition of Bone/Cartilage Destruction

2018 ◽  
Vol 4 (1) ◽  
pp. 121-131
Author(s):  
Koichiro Ishikawa ◽  
Junichiro Ishikawa
Keyword(s):  
Joint Destruction ◽  
Cartilage Destruction ◽  
Sodium Aurothiomalate ◽  
Radiographic Outcomes ◽  
Smallest Detectable Change ◽  
Receptor Activator ◽  
Daily Dose ◽  
Suppression Mechanism ◽  
Disease Modifying ◽  
Rheumatic Drug

Objective: To elucidate the radiographic outcomes for rheumatoid arthritis (RA) patients using the synthetic disease-modifying antirheumatic drug (sDMARD) Iguratimod (IGU) and other DMARDs including injectable sodium aurothiomalate, bucillamine, salazosulphapyridine, infliximab, etanercept, tocilizumab and/or abatacept.Patients and Methods: 213 patients were enrolled in this study. Total Genant-modified Sharp scores (GSS) of hands/wrists and feet at baseline and at week 104 were calculated in 31 RA patients treated with a daily dose of 25 mg or 50 mg for 104 weeks.Results: Total GSS of 31 patients at week 104 showed no progression (total GSS  <= 0.84: the smallest detectable change) in 16 (52%) patients with a mean score reduction (95% CI) of-4.3 (-8.1 ~ -0.5) (p < 0.05).Conclusion: Treatment with the sDMARD, IGU showed no radiographic progression in 16 (52%) RA patients at week 104. Concerning the suppression mechanism of joint destruction by IGU and other DMARDs, we speculate that DMARDs prevent bone/cartilage destruction by inhibiting the receptor activator of nuclear factor-kappa B (NF- kB) lig and (RANKL) and through other antirheumatic actions.

Rheumatoid Arthritis

2014 ◽  
pp. 231-241
Author(s):  
Derrick J. Todd ◽  
Jonathan S. Coblyn
Keyword(s):  
Rheumatoid Arthritis ◽  
Laboratory Tests ◽  
Treatment Options ◽  
Joint Destruction ◽  
Autoimmune Disorder ◽  
Cartilage Destruction ◽  
Pharmacologic Treatment ◽  
Life Threatening ◽  
Disease Modifying ◽  
Over Time

Rheumatoid arthritis (RA) is an idiopathic systemic autoimmune disorder that primarily involves the joints. It causes inflammation of the synovium (synovitis) that can lead to cartilage destruction and bone erosions. Extra-articular manifestations may also occur. The diagnosis of RA is based on a combination of clinical features, laboratory tests, and imaging studies. In recent years, great strides have been made in the pharmacologic treatment of RA, which consists primarily of immunosuppressive or immunomodulatory therapy with disease-modifying antirheumatic drugs (DMARDs). It is important to understand that RA is a heterogeneous disorder: some patients may have a severe, rapidly progressive disease with life-threatening extra-articular symptoms, whereas other patients may have indolent symptoms with little if any joint destruction over time. This point is important when making a diagnosis of RA, and especially when considering treatment options.

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 Disease-Modifying Adjunctive Therapy (DMAT) in Osteoarthritis—The Biological Effects of a Multi-Mineral Complex, LithoLexal® Joint—A Review

2021 ◽  
Vol 11 (4) ◽  
pp. 901-913
Author(s):  
Erik Fink Eriksen ◽  
Osvandre Lech ◽  
Gilberto Yoshinobu Nakama ◽  
Denise M. O’Gorman
Keyword(s):  
Adjunctive Therapy ◽  
Chondroitin Sulphate ◽  
Biological Effects ◽  
Joint Destruction ◽  
Molecular Medicine ◽  
Inflammatory Disorder ◽  
Walking Ability ◽  
Contributing Factors ◽  
Mineral Complex ◽  
Disease Modifying

Modern advances in molecular medicine have led to the reframing of osteoarthritis as a metabolically active, inflammatory disorder with local and systemic contributing factors. According to the ‘inflammatory theory’ of osteoarthritis, immune response to an initial damage is the key trigger that leads to progressive joint destruction. Several intertwined pathways are known to induce and govern articular inflammation, cartilage matrix degradation, and subchondral bone changes. Effective treatments capable of halting or delaying the progression of osteoarthritis remain elusive. As a result, supplements such as glucosamine and chondroitin sulphate are commonly used despite the lack of scientific consensus. A novel option for adjunctive therapy of osteoarthritis is LithoLexal® Joint, a marine-derived, mineral-rich extract, that exhibited significant efficacy in clinical trials. LithoLexal® has a lattice microstructure containing a combination of bioactive rare minerals. Mechanistic research suggests that this novel treatment possesses various potential disease-modifying properties, such as suppression of nuclear factor kappa-B, interleukin 1β, tumor necrosis factor α, and cyclooxygenase-2. Accordingly, LithoLexal® Joint can be considered a disease-modifying adjunctive therapy (DMAT). LithoLexal® Joint monotherapy in patients with knee osteoarthritis has significantly improved symptoms and walking ability with higher efficacy than glucosamine. Preliminary evidence also suggests that LithoLexal® Joint may allow clinicians to reduce the dose of nonsteroidal anti-inflammatory drugs in osteoarthritic patients by up to 50%. In conclusion, the multi-mineral complex, LithoLexal® Joint, appears to be a promising candidate for DMAT of osteoarthritis, which may narrow the existing gap in clinical practice.

scholarly journals Absence of Fms-like tyrosine kinase 3 ligand (Flt3L) signalling protects against collagen-induced arthritis

2013 ◽  
Vol 74 (1) ◽  
pp. 211-219 ◽  
Author(s):  
M I P Ramos ◽  
O N Karpus ◽  
P Broekstra ◽  
S Aarrass ◽  
S E Jacobsen ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Acute Phase ◽  
Ex Vivo ◽  
Late Phase ◽  
Joint Destruction ◽  
Chronic Phase ◽  
Foxp3 Expression ◽  
Cartilage Destruction ◽  
Collagen Induced Arthritis ◽  
Clinical Arthritis

ObjectiveComprehending the mechanisms that regulate activation of autoreactive T cells and B cell antibody production is fundamental for understanding the breakdown in self-tolerance and development of autoimmunity. Here we studied the role of Fms-like tyrosine kinase 3 ligand (Flt3L) signalling in the pathogenesis of collagen-induced arthritis (CIA).MethodsCIA was induced in mice lacking Flt3L (Flt3L−/−)and wild-type (WT) littermates (C57/BL6, 8–10 weeks old). Mice were killed in the initial phase (acute phase: experiment 1) and late phase (chronic phase: experiment 2) of the disease. Arthritis severity was assessed using a semiquantitative scoring system (0–4), and histological analysis of cellular infiltration, cartilage destruction and peptidoglycan loss was performed. Phenotypic and functional analysis of T and B cells, FoxP3 expression, activation and lymphocyte costimulatory markers, and cytokine production were performed ex vivo by flow cytometry in lymph nodes. Serum collagen type II (CII)-specific antibodies were measured by ELISA.ResultsFlt3L−/−mice showed a marked decrease in clinical arthritis scores and incidence of arthritis in both acute and chronic phases of CIA compared with WT mice. Moreover, decreased synovial inflammation and joint destruction was observed. Both the magnitude and quality of T cell responses were altered in Flt3L−/−. In the acute phase, the amount of CII-specific IgG2a antibodies was lower in Flt3L−/−than WT mice.ConclusionsThese results strongly suggest a role for Flt3L signalling in the development of arthritis.

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