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ID PMID Title PublicationDate abstract
32063468 Radiographic effects observed in the coronal view after medial malleolar osteotomy at tota 2020 Nov BACKGROUND: When soft tissue balance is not acceptable at total ankle arthroplasty (TAA) for rheumatoid varus deformity, medial malleolar osteotomy has been performed. At the same time, the shape of the ankle joint changes after soft tissue balancing with such an osteotomy, however there is few information for the radiographic findings after the osteotomy. Thus, radiographic changes in the coronal view of such cases were investigated. METHODS: JSSF-RA foot and ankle scale and SAFE-Q scores were determined along with pre/postoperative radiographic parameters of the ankle joint in 70 ankles (65 patients) with rheumatoid arthritis followed for a mean of 7.9 years (range, 2-16 years) after TAA. Seven ankles were excluded because those underwent lateral or lateral/medial malleolar osteotomy. Twenty-seven ankles underwent medial malleolar osteotomy, and compared with 36 ankles without osteotomy. RESULTS: All ankles achieved bone union after medial malleolar osteotomy, and the tibial medial malleolus (TMM) angle was significantly decreased [30.3°-19.1°] following significant valgus correction [TC angle: -2.7° to 0.5°]. The gap due to medial soft tissue tightness was significantly improved by medial malleolar osteotomy [4.95° to 0.7°]. Lateral malleolar fractures sometimes occurred (19%: 5/27 ankles) at valgus correction, but they healed completely without any internal fixation. CONCLUSION: Medial malleolar osteotomy was useful in rheumatoid varus ankle for not only controlling the soft tissue balance, but also providing a stabilized shape of the ankle joint. Lateral malleolar fractures were caused by valgus correction following medial malleolar osteotomy in some cases, but all fractures were completely healed without any internal fixation.
31615315 Plasma pentraxin 3 is associated with progression of radiographic joint damage, but not ca 2020 Nov Background: Pentraxin 3 (PTX3) has an important role in inflammation, immunity, and atherosclerosis. Rheumatoid arthritis (RA) is a chronic inflammatory disease featuring both joint damage and atherosclerosis. We investigated whether the plasma PTX3 level was associated with progression of joint destruction and subclinical atherosclerosis in RA patients.Methods: Plasma PTX3 levels were measured in 72 women with RA and 80 female control subjects. In RA patients, we also evaluated clinical characteristics, medications, and at one and three years, joint damage and atherosclerosis. Then we investigated whether PTX3 was associated with progression of joint destruction or an increase of carotid intima-media thickness (IMT).Results: Plasma PTX3 levels were significantly higher in the RA patients than in healthy controls (4.05 ± 2.91 ng/mL vs. 1.61 ± 1.05 ng/mL, p < .001). By multivariate linear regression analysis, the plasma pentraxin 3 level was independently associated with radiographic progression of joint damage for 3 years in the RA patients after adjustment for age, disease duration, body mass index, rheumatoid factor, MMP-3, Disease Activity Score 28-ESR, postmenopausal status, current use of corticosteroids and biologic use. On the other hands, pentraxin 3 was not associated with an increase of carotid intima-media thickness in RA patients.Conclusion: Female RA patients had elevated plasma PTX3 levels compared with control female subjects. PTX3 was independently associated with radiographic progression of joint damage in the RA patients, but not with carotid atherosclerosis.
32390383 Circulating C-Reactive Protein to Prealbumin Ratio and Prealbumin to Fibrinogen Ratio are 2020 May 1 BACKGROUND: The C-reactive protein to prealbumin ratio (CPR) and prealbumin to fibrinogen ratio (PFR) are two new inflammatory markers that were reported to have predictive value for the assessment of systemic inflammatory disease. The aim of the present study was to explore the relationship between these two markers and the Disease Activity Score of 28 joints (DAS-28) in rheumatoid arthritis (RA). METHODS: A total of 170 RA patients and 120 healthy individuals were enrolled in this retrospective study. Correlations of CPR and PFR with the disease activity of RA were analyzed. Receiver-operating characteristic (ROC) curves for CPR and PFR were generated to determine the discriminative ability by calculating the areas under the curve (AUC). RESULTS: Compared with healthy controls, RA patients showed a significantly lower PFR (p < 0.001) and higher CPR (p < 0.001). CPR was positively correlated with C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and DAS-28 score (r = 0.957, p < 0.001, r = 0.781, p < 0.001, r = 0.729, p < 0.001, respectively), whereas the PFR was negatively correlated with CRP, ESR, and DAS-28 score (r = -0.817, p < 0.001, r = -0.805, p < 0.001, r = -0.739, p < 0.001, respectively) in RA patients. ROC curve analysis showed that the CPR and PFR had a high level of AUC (AUC = 0.943 and AUC = 0.912, respectively). CONCLUSIONS: The CPR and PFR are two promising novel inflammatory markers for assessing disease activity in RA patients.
31325305 Predictors of successful discontinuation of biologic and targeted synthetic DMARDs in pati 2020 Feb 1 OBJECTIVE: To systematically review possible predictors of successful discontinuation of biologic or targeted synthetic DMARDs (b/tsDMARDs) in RA patients in remission or low disease activity. METHODS: MEDLINE database and Cochrane Library were scanned for studies that discontinued b/tsDMARDs in remission/low disease activity and searched for predictors of successful discontinuation. Additionally, EULAR and ACR meeting abstracts were hand searched. RESULTS: Thirty-four studies with a total of 5724 patients were included. Predictors of successful b/tsDMARD discontinuation were (number of studies): low disease activity (n = 13), better physical function (n = 6), low or absence of rheumatoid factor (n = 5) or ACPA (n = 3), low levels of CRP (n = 3) or ESR (n = 3), shorter disease duration (n = 3), low signals of disease activity by ultrasound (n = 3). Only one study with high risk of bias was identified on tsDMARD discontinuation. CONCLUSION: Several predictors of successful bDMARD discontinuation were identified. Although studies are heterogeneous, these predictors may inform clinical decision making in patients who are considered for a potential bDMARD discontinuation.
33086966 A case of granulomatous myositis in a patient with rheumatoid arthritis receiving anti-TNF 2020 Jan A 66-year old woman with a 14-year history of rheumatoid arthritis (RA) and uveitis was admitted to our department for evaluation of a mass in the left neck. Fourteen months prior to this admission the patient was started on golimumab. Serum creatine kinase (CK) level was elevated and myositis-specific and -associated antibodies were negative. Manual muscle test showed weakness in the neck flexor, sternocleidomastoid and deltoid muscles. Magnetic resonance imaging (MRI) of the neck, erector muscle of spine, breech, thigh and lower thigh demonstrated high-intensity lesions in the muscles in short-tau inversion recovery images. Electromyography in the right deltoid detected fibrillation potentials. Muscle biopsy from the left neck mass showed granulomatous myositis. Muscle weakness improved and CK levels normalized after discontinuation of golimumab. We report a case of granulomatous myositis under anti-TNF-α treatment for RA.
32321893 Effective Treatment with Tocilizumab in a Rheumatoid Arthritis Patient Complicated with Hu 2020 Aug 1 A 61-year-old woman with human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy (HAM)/tropical spastic paraparesis (TSP) and interstitial pneumonia (IP) was admitted to our hospital. She complained of sicca symptoms, polyarthralgia, and swollen joints. She was diagnosed with rheumatoid arthritis (RA) and Sjögren's syndrome. Methotrexate and anti-tumor necrosis factor therapy were not utilized because of the inclusion of severe respiratory disorders among the complications and the neurological symptoms of HAM/TSP. Tocilizumab monotherapy improved the RA disease activity without exacerbating HAM/TSP. The present case suggests that tocilizumab might be a suitable treatment option in patients with RA and HAM/TSP.
33198301 Activation of c-Jun N-Terminal Kinase, a Potential Therapeutic Target in Autoimmune Arthri 2020 Nov 12 The c-Jun-N-terminal kinase (JNK) is a critical mediator involved in various physiological processes, such as immune responses, and the pathogenesis of various diseases, including autoimmune disorders. JNK is one of the crucial downstream signaling molecules of various immune triggers, mainly proinflammatory cytokines, in autoimmune arthritic conditions, mainly including rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis. The activation of JNK is regulated in a complex manner by upstream kinases and phosphatases. Noticeably, different subtypes of JNKs behave differentially in immune responses. Furthermore, aside from biologics targeting proinflammatory cytokines, small-molecule inhibitors targeting signaling molecules such as Janus kinases can act as very powerful therapeutics in autoimmune arthritis patients unresponsiveness to conventional synthetic antirheumatic drugs. Nevertheless, despite these encouraging therapies, a population of patients with an inadequate therapeutic response to all currently available medications still remains. These findings identify the critical signaling molecule JNK as an attractive target for investigation of the immunopathogenesis of autoimmune disorders and for consideration as a potential therapeutic target for patients with autoimmune arthritis to achieve better disease control. This review provides a useful overview of the roles of JNK, how JNK is regulated in immunopathogenic responses, and the potential of therapeutically targeting JNK in patients with autoimmune arthritis.
33162488 Familial Mediterranean fever phenotype progression into anti-cyclic citrullinated peptide 2020 Dec 10 Familial Mediterranean fever (FMF) is caused by dysfunction of the MEFV gene product, pyrin. Here we report a case of FMF phenotype which developed into rheumatoid arthritis (RA), based on a positive result for anti-cyclic citrullinated peptide (CCP) antibody (Ab). A 42-year-old woman presented to our clinic with more than 6 months of intermittent arthralgia in the wrists, feet, and fingers associated with menstruation. No fever was reported and there was no family history of FMF or other autoimmune diseases. Laboratory tests revealed elevated C-reactive protein (CRP) and rheumatoid factor (RF). Tests for autoantibodies including anti-CCP Ab, antinuclear Ab, and anti-DNA Ab were all negative. Genetic analysis identified an R304R homozygous mutation in MEFV; however, the pathological significance is unclear because this mutation does not cause amino acid substitution. We diagnosed incomplete FMF phenotype despite the lack of fever due to periodic arthritis, lack of autoantibodies, and complete resolution of arthritis following colchicine treatment within a day. Several months later, increased stiffness and arthralgia persistently occurred in finger joints on both sides. Ultrasonography revealed synovitis at the metacarpophalangeal and metatarsophalangeal joints. Laboratory analysis revealed the patient to be positive for anti-CCP Ab. Therefore, we finally diagnosed RA. Her arthritis diminished following administration of methotrexate and salazosulfapyridine. We consider the possibility that pyrin dysfunction may have affected the acquired immunity, contributing to the onset of RA as an autoimmune disease. This is an interesting case of equivalent FMF progressing into RA and will be valuable to raise awareness of a continuum from autoinflammatory to autoimmune disease.
33526731 COMORBID CONDITION - DIABETES MELLITUS WITH CO-EXISTENT RAYNAUD'S SYNDROME IN PATIENTS WIT 2020 Dec The most common comorbidities in patients with rheumatic diseases include cardiovascular diseases (CVD), liver and biliary tract infection, lung diseases, amyloidosis, fractures of different localizations, malignant neoplasms, metabolic disorders and diabetes mellitus (DM). The aim of study was to investigate the clinical course of DM and rheumatoid arthritis (RS) in patients with RA using laboratory and instrumental research methods. There were examined 85 patients with RA who were treated in the rheumatology department of Ivano-Frankivsk Central City Clinical Hospital. The patients' age ranged from 40 to 70 years. Endothelial dysfunction (ED) signs were observed in 76 (89.4%) patients. ED was diagnosed in all patients with RA, co-existent RS and DM. In the patients with RA and those with RA and co-existent RS, impaired EDVBA was detected. In the patients of Group II, the indicator of EDVBA (6.5±0.2%) was significantly lower as compared to the patients of Group I (8.8±0.3%) (р<0.05). The levels of both CRP and TNF-α, serving as non-specific inflammatory markers, were significantly higher (29.37±3.56 mg/l, p<0.01) in the patients with RS as compared to the patients with RA only (23.89±1.77 mg/l). A detailed study of the pathophysiological and immunological features of the clinical course of secondary RS will allow us to optimize its treatment schemes in patients with RA, reduce clinical and laboratory manifestation of RA and improve quality of life in such patients, especially those with a comorbidity.
30120021 Antisynthetase syndrome complicating the course of established case with rheumatoid arthri 2020 Sep A 52-year-old male patient developed RA in March 2009 at the age of 43, with symmetric polyarthritis and active synovitis affecting hands, knees, ankles and both feet without symptoms or signs suggestive of extra-articular features. Laboratory investigations showed negative RF and positive anti-CCP antibodies, negative ANA, negative anti-dsDNA antibodies; the X-rays of both hands showed typical erosive changes in RA and fulfilled the new ACR/EULAR (2010) criteria of RA. The patient achieved remission on a combination of DMARDs. He did well until January 2017 when he developed acute onset of progressive chest pain, dyspnea, and acute respiratory failure. High-resolution CT of the lung showed extensive areas of ground glass veiling, and interstitial subpleural infiltrates were found consistent with aggressive interstitial lung disease (ILD). Autoantibodies against extractable nuclear antigens were screened and showed positive results for anti-RO and anti-Jo1 autoantibodies. The positive anti-Jo1was an expression of anti-synthetase syndrome complicating the RA course and explained the rapidly aggressive course of ILD.
32314010 Coronavirus Disease 19 (COVID-19) complicated with pneumonia in a patient with rheumatoid 2020 Jun In December 2019, numerous coronavirus disease 2019 (COVID-19) cases were reported in Wuhan, China, which has since spread throughout the world. However, its impact on rheumatoid arthritis (RA) patients is unknown. Herein, we report a case of COVID-19 pneumonia in a 61-year-old female RA patient who was receiving conventional disease-modifying antirheumatic drugs (cDMARDs). The patient presented with a 4-day history of myalgia and febrile sensation. COVID-19 was confirmed by real-time polymerase chain reaction (PCR). Chest X-ray showed increased opacity on the right lower lung area, and C-reactive protein level was slightly elevated. The patient was treated with antiviral agents (lopinavir/ritonavir), and treatment with cDMARDs was discontinued except hydroxychloroquine. Her symptoms and laboratory results gradually improved. Three weeks later, real-time PCR for COVID-19 showed negative conversion, and the patient was discharged without any complications.
31896547 Gingimaps: Protein Localization in the Oral Pathogen Porphyromonas gingivalis. 2020 Feb 19 Porphyromonas gingivalis is an oral pathogen involved in the widespread disease periodontitis. In recent years, however, this bacterium has been implicated in the etiology of another common disorder, the autoimmune disease rheumatoid arthritis. Periodontitis and rheumatoid arthritis were known to correlate for decades, but only recently a possible molecular connection underlying this association has been unveiled. P. gingivalis possesses an enzyme that citrullinates certain host proteins and, potentially, elicits autoimmune antibodies against such citrullinated proteins. These autoantibodies are highly specific for rheumatoid arthritis and have been purported both as a symptom and a potential cause of the disease. The citrullinating enzyme and other major virulence factors of P. gingivalis, including some that were implicated in the etiology of rheumatoid arthritis, are targeted to the host tissue as secreted or outer-membrane-bound proteins. These targeting events play pivotal roles in the interactions between the pathogen and its human host. Accordingly, the overall protein sorting and secretion events in P. gingivalis are of prime relevance for understanding its full disease-causing potential and for developing preventive and therapeutic approaches. The aim of this review is therefore to offer a comprehensive overview of the subcellular and extracellular localization of all proteins in three reference strains and four clinical isolates of P. gingivalis, as well as the mechanisms employed to reach these destinations.
33087004 A case of acute diffuse large B cell lymphoma in an anti-human T-cell leukaemia virus type 2020 Jul A 70-year-old woman was hospitalised due to jaundice and fever. She was diagnosed with rheumatoid arthritis (RA) at 54 years of age. Treatment with methotrexate (MTX) was successful, and her RA was in remission. Five weeks before the hospitalisation, she was diagnosed with optic neuritis due to a decline in the visual acuity of the right eye. She was treated with methylprednisolone pulse therapy, followed by prednisolone (PSL), before the hospitalisation, which were not effective. Blood tests showed increased C-reactive protein (CRP) levels, liver injury, and thrombocytopenia. Abdominal echo revealed numerous enlarged lymph nodes in the hepatic portal region. Malignant lymphoma was suspected due to high serum levels of soluble interleukin-2 receptor. None of the treatments were effective, and she died on the fifth hospital day. Diffuse large B cell lymphoma was diagnosed during the autopsy, which showed infiltration of CD20-positive atypical lymphocytes in almost all organs. Since she was taking MTX, she was diagnosed with immunosuppressive drug-associated lymphoproliferative disease (LPD). Anti-human T-cell leukaemia virus type 1 (HTLV-1) antibody was detected in her serum after her death; however, adult T cell leukaemia/lymphoma was not observed. LPD develops during the treatment of RA with disease modifying anti-rheumatic drugs; however, a rapid clinical course leading to death is rarely observed. Previous reports suggest that T cell dysregulation observed in HTLV-1 may contribute towards the development of B cell lymphoma. We have discussed the possible roles of HTLV-1 in LPD development in this case.
32130057 Clinical Profile of Patients with Scleritis in Bangladesh. 2021 Aug 18 Purpose: To analyze clinical profile of the patients with scleritis in a tertiary care eye hospital in Bangladesh.Method: Retrospective analysis of 111 eyes of 79 patients of scleritis between January 2012 and May 2018.Result: The study observed a relative younger mean age and equal gender distribution. Diffuse anterior scleritis (43%) was the most common type of scleritis. Rheumatoid arthritis (10%) was the most common systemic disease followed by granulomatosis with polyangiitis (5%) and tuberculosis (2.5%). Fifty-eight patients (73.4%) required immunosuppressive agents.Conclusion: The current study highlighted a distinct pattern and profile of scleritis patients in Bangladesh.
31584316 A novel arthritis model induced by wind, damp, cold and heat in female rats. 2020 Oct Animal models are in constant development to benefit scientific research. Rheumatoid arthritis (RA) is considered a very complex disease due to its complicated pathogenesis, and patients with rheumatic disease around the world are still unable to obtain effective, simple and curable treatment. In order to obtain a clear insight into the pathogenesis of RA, a rat model was established based on the concept of Bi syndrome in Traditional Chinese Medicine by simulating the conditions of RA as much as possible via the change in the physical conditions wind, damp, cold and heat (WDCH). For the first time, a new WDCH-induced RA model in female rats was successfully established and evaluated by body-weight change, paw swelling, blood cells analysis, spleen and thymus coefficients, autoantibodies and serum cytokine changes and histopathology. This model is characterised by its objectivity, no exogenous induction, short modelling time, extremely elevated expression level of autoantibodies and obvious histopathological change. The establishment of such a new model may provide more benefits in the research of the pathogenesis of RA.
31742738 A directly GP130-targeting small molecule ameliorates collagen-induced arthritis (CIA) by 2020 Apr Rheumatoid arthritis is a chronic inflammatory disease associated with joint inflammation and destruction driven by T helper 17 (Th17) cells. Interleukin-6 (IL-6) is secreted by many cell types, including macrophages and synovial fibroblasts. It induces the differentiation and function of Th17 cells that can increase lymphocytic infiltration in the joint. LMT-28 can suppress IL-6 signalling through direct binding to glycoprotein-130 and alleviate inflammatory diseases such as rheumatoid arthritis and inflammatory bowel disease. The purpose of this study was to assess whether LMT-28 could potently inhibit Th17 differentiation and to determine the mechanism involved in the attenuating effect of LMT-28 on rheumatoid arthritis through the IL-6 signalling pathway. LMT-28 reduced the arthritis score and showed protective effects against bone and cartilage destruction in collagen-induced arthritis (CIA) mice. In mice with CIA, LMT-28 markedly decreased serum levels of IL-6, TNF and IL-1β compared to vehicle control. Moreover, LMT-28 attenuated Th17 cell activation in lymph nodes of CIA mice. We demonstrated that LMT-28 suppressed differentiation of Th17 in mouse splenocytes and human peripheral blood mononuclear cells (PBMCs). Additionally, LMT-28 inhibited phosphorylation of GP130, STAT3 and ERK induced by Hyper-IL-6 in human fibroblast-like synoviocytes (FLS). Collectively, these results suggest that LMT-28 can inhibit differentiated/activated-Th17 cells in rheumatoid arthritis by blocking activation of the STAT3 pathway. LMT-28 can attenuate rheumatoid arthritis by inhibiting differentiation/activation of Th17 cells and suppressing the proliferation and signalling activation of the IL-6/solubleIL-6 receptor complex stimulated FLS.
32377996 Serum homocysteine levels and their association with clinical characteristics of inflammat 2020 Nov OBJECTIVE: The aim of our study was to explore the serum levels of homocysteine (Hcy) and its association with clinical characteristics in patients with different types of inflammatory arthritis. METHODS: A total of 242 patients diagnosed with inflammatory arthritis (which included rheumatoid arthritis (RA), ankylosing spondylitis (AS), and gout), 49 with osteoarthritis (OA), and 36 with hyperuricaemia (HUA) and 81 healthy controls (HCs) were enrolled for comparisons. RESULTS: The serum Hcy levels of patients with RA, AS, and OA were comparable with those of the HC group (P > 0.05). However, the serum level of Hcy was significantly higher in patients with gout than in HCs (18.75 ± 9.98 vs. 14.20 ± 6.22 μmol/L, P = 0.007). In addition, we found that the serum Hcy level was much higher in RA patients who received methotrexate (MTX) therapy without folic acid supplementation than in those who received MTX with folic acid supplementation (13.39 ± 4.80 vs. 9.41 ± 2.04 μmol/L, P = 0.001). Furthermore, there was a positive correlation between uric acid and Hcy in patients without uric acid-lowering treatment (r = 0.537, P = 0.002), but the correlation was eliminated after adjusting uric acid-lowering treatment (r = 0.139, P = 0.393). Finally, consistent with the above findings, hyperhomocysteinaemia (HHcy) was more common in gout patients (P < 0.05). CONCLUSION: Screening for HHcy in patients with gout and RA, especially RA patients treated with MTX, might be necessary, and patients with HHcy might benefit from earlier supplementation with folic acid. Key Points • Serum homocysteine (Hcy) was elevated and the rate of hyperhomocysteinaemia (HHcy) was significantly higher in gout. • Rheumatoid arthritis (RA) patients who received methotrexate (MTX) treatment without folic acid supplementation showed higher serum Hcy than those who received MTX treatment with folic acid supplementation. • The serum Hcy level was positively correlated with age in only RA patients. • Serum Hcy was correlated with uric acid in gout patients, but the correlation was eliminated after adjusting uric acid-lowering treatment.
32971299 Three cases of rheumatoid meningitis with elevated CSF neopterin levels. 2020 Nov 15 Rheumatoid meningitis (RM) is a rare but treatable central nervous system (CNS) manifestation of rheumatoid arthritis (RA) with various clinical presentations and atypical cerebrospinal fluid (CSF) findings. There are no established biomarkers for RM, making diagnosis a challenge. Herein, we present three cases of RM: two patients with RA diagnosis and one without. CSF analysis showed pleocytosis in only one case. In contrast, CSF neopterin levels were elevated in all three cases and decreased after steroid therapy. This study suggests that CSF neopterin levels may be a useful biomarker for diagnosing and therapeutically monitoring CNS inflammation in patients with RM.
32452368 [Protein arginine deiminase of oral microbiome plays a causal role in the polyarthritis rh 2020 May In the last decade, the association between the periodontitis and rheumatoid arthritis (RA) has been established, suggesting that oral microbiome plays a causal role by initiating this chronic autoimmune inflammatory disease of articulation. Both pathogenesis are similar in term of chronic inflammation, tissue breakdown and bone resorption. Molecular aspects have also revealed that citrullination, a post-translational modification catalyzed by peptidyl-arginine deiminases (PADs), is involved in both diseases. For RA, citrullinated proteins production leads to the synthesis the of anti-citrullinated protein antibodies triggering the loss of immune tolerance. In humans, five PADs have been identified. Recently, studies have found that only Porphyromonas species possess PAD. Thus, a major periodontal pathogen, Porphyromonas gingivalis, is able to generate citrullinated epitopes, and could consequently induce anti-citrullinated protein antibodies. In this review, citrullination process, periodontitis and RA are described to put them in relation with molecular, clinical and epidemiological studies establishing the association between periodontitis and RA.
32477372 Transcriptional Regulation of Osteoclastogenesis: The Emerging Role of KLF2. 2020 Dysregulation of osteoclastic differentiation and its activity is a hallmark of various musculoskeletal disease states. In this review, the complex molecular factors underlying osteoclastic differentiation and function are evaluated. The emerging role of KLF2 in regulation of osteoclastic differentiation is examined, specifically in the context of rheumatoid arthritis in which it has been most extensively studied among the musculoskeletal diseases. The therapies that exist to manage diseases associated with osteoclastogenesis are numerous and diverse. They are varied in their mechanisms of action and in the outcomes they produce. For this review, therapies targeting osteoclasts will be emphasized, though it should be noted that many therapies exist which bolster the action of osteoblasts. A new targeted molecular approach is under investigation for the future potential therapeutic development of rheumatoid arthritis.