Osteoarthritis treatment should contemplate the improvement of subchondral bone quality. This therapeutic approach must be individualized in each patient depending on the BMD status and the ...physiopathological subgroup of osteoarthitis (OA). BMD: bone mineral density; SB: subchondral bone.
Osteoarthritis (OA), the most common form of arthritis, is a debilitating and progressive disease that has become a major cause of disability and impaired quality of life in the elderly. OA is considered an organ disease that affects the whole joint, where the subchondral bone (SB) plays a crucial role. Regardless of whether SB alterations precede cartilage damage or appear during the evolution of the disease, SB is currently recognised as a key target in OA treatment. In fact, bone abnormalities, especially increased bone turnover, have been detected in the early evolution of some forms of OA. Systemic osteoporosis (OP) and OA share a paradoxical relationship in which both high and low bone mass conditions may result in induction and/or OA progression. Recent findings suggest that some drugs may be useful in treating both processes simultaneously, at least in a subgroup of patients with OA and OP. This review focuses on the role of SB in OA pathogenesis, describing relevant underlying mechanisms involved in the process and examining the potential activity as disease-modifying anti-osteoarthritic drugs (DMOADs) of certain SB-targeting agents currently under study.
Polymyalgia rheumatica González-Gay, Miguel A; Matteson, Eric L; Castañeda, Santos
The Lancet (British edition),
10/2017, Letnik:
390, Številka:
10103
Journal Article
Recenzirano
Polymyalgia rheumatica is an inflammatory disease that affects the shoulder, the pelvic girdles, and the neck, usually in individuals older than 50 years. Increases in acute phase reactants are ...typical of polymyalgia rheumatica. The disorder might present as an isolated condition or in association with giant cell arteritis. Several diseases, including inflammatory rheumatic and autoimmune diseases, infections, and malignancies can mimic polymyalgia rheumatica. Imaging techniques have identified the presence of bursitis in more than half of patients with active disease. Vascular uptake on PET scans is seen in some patients. A dose of 12·5–25·0 mg prednisolone daily or equivalent leads to rapid improvement of symptoms in most patients with isolated disease. However, relapses are common when prednisolone is tapered. Methotrexate might be used in patients who relapse. The effectiveness of biological therapies, such as anti-interleukin 6, in patients with polymyalgia rheumatica that is refractory to glucocorticoids requires further investigation. Most population-based studies indicate that mortality is not increased in patients with isolated disease.
Osteoporosis has been classically considered a comorbidity of rheumatoid arthritis (RA). However, recent advances in the pathogenesis of osteoporosis in RA have shown a close interplay between cells ...of the immune system and those involved in bone remodeling, introducing new actors into the classic route in which osteoclast activation is related to the RANK/RANKL/OPG pathway. In fact, the inflammatory state in early stages of RA, mediated by interleukin (IL)-1, IL-6, IL-8 and tumor necrosis factor (TNF)-α has the ability to activate and differentiate osteoclasts not only through their relationship with RANKL, but also through the Wnt/DKK1/sclerostin pathway, leading to bone loss. The role of synovial fibroblasts and activated T lymphocytes in the expression of the RANKL system and its connection to bone destruction is also depicted. In addition, autoantibodies such as rheumatoid factor and anti-citrullinated protein antibodies are other pathogenic mechanisms for the development of bone erosions and systemic osteoporosis in RA, even before the onset of arthritis. The aim of this review is to unravel the relationship between different factors involved in the development of osteoporosis in RA patients, both the classic factors and the most novel, based on the relationship of autoantibodies with bone remodeling. Furthermore, we propose that bone mineral density measured by different techniques may be helpful as a biomarker of severity in early arthritis patients.
Interstitial lung disease (ILD) is one of the most relevant extra-articular manifestations of rheumatic diseases resulting in a substantial increase in morbidity and mortality. Early diagnosis and ...close monitoring to identify patients at high risk of progression are crucial to establish the need for targeted treatment with immunomodulatory and antifibrotic drugs, with potential ability to change the course of the disease. However, there are unmet needs in this field as pulmonary auscultation, chest radiography, or pulmonary function studies do not allow identification of the most incipient stages of the disease. High-resolution computed tomography (HRCT), which is the current gold standard for diagnosis and evolutionary control, is problematic owing to ionizing radiation, cost, and accessibility. In this context, lung ultrasound (LUS) is an attractive tool in a growing research and validation process. The identification of vertical artifacts, such as B lines, and alterations of the pleural line present a good correlation with the presence of ILD by HRCT and have a good concordance with the extent and severity of the disease, with sensitivity and negative predictive values of up to 100%. Regarding the monitoring of the evolution, the validation process of LUS is in a more preliminary phase but data is encouraging. All this, together with its safety, accessibility, low cost, and good patient acceptance, postulate LUS as a useful tool for the screening of ILD and for the optimization of the indications of HRCT.
Key Points
• The good sensitivity and negative predictive values of LUS postulate this technique as a useful tool for the screening of ILD and for the optimization of the indications of HRCT in rheumatic diseases.
Adult-onset Still´s disease (AOSD) is a systemic inflammatory condition that affects mainly young people. The clinical course consists of two distinctive patterns: one with a predominance of systemic ...symptoms and another manifested by progressive chronic polyarthritis. Glucocorticoids remain the mainstay in the treatment of AOSD. However, biologic therapies are often required to achieve clinical remission and allow glucocorticoid discontinuation. Areas covered: The review summarizes the main retrospective and prospective studies, and case series on the use of the anti-interleukin (IL)-6 receptor tocilizumab in AOSD. Expert opinion: Since IL-6 serum levels are highly increased in both active systemic and polyarticular phenotypes, IL-6 blockade was considered to be a plausible therapeutic option for the management of AOSD. Tocilizumab, the only anti-IL-6-receptor antagonist currently available for AOSD, has proved to be effective for the management of refractory AOSD patients, including those with life-threatening complications. Nevertheless, there are some reports describing patients who are refractory to any therapy. Future research should focus on the identification of prognostic biomarkers that help us to tailor an individualized treatment for each type of patient and in the search of new disease activity indices that help us to monitor the response to the therapy more closely.
Osteoarthritis (OA) affects all articular tissues and finally leads to joint failure. Although articular tissues have long been considered unresponsive to estrogens or their deficiency, there is now ...increasing evidence that estrogens influence the activity of joint tissues through complex molecular pathways that act at multiple levels. Indeed, we are only just beginning to understand the effects of estrogen deficiency on articular tissues during OA development and progression, as well as on the association between OA and osteoporosis. Estrogen replacement therapy and current selective estrogen receptor modulators have mixed effectiveness in preserving and/or restoring joint tissue in OA. Thus, a better understanding of how estrogen acts on joints and other tissues in OA will aid the development of specific and safe estrogen ligands as novel therapeutic agents targeting the OA joint as a whole organ.
Abstract Adult-onset Still's disease (AOSD) is a rare systemic inflammatory disorder mainly characterized by persistent high spiking fevers, evanescent rash, and joint involvement. The pathogenesis ...of AOSD is only partially known, but pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1, IL-6, IL-18, and IFN-γ seem to play a major role in this disorder. AOSD is at the crossroad of auto-inflammatory syndromes and autoimmune diseases. It is diagnosed by exclusion to determine the presence of high serum ferritin levels, which is usually >1000 μg/L. AOSD is generally treated with non-steroidal anti-inflammatory drugs, corticosteroids, and disease-modifying anti-rheumatic drugs (DMARDs). Although information on biologic therapy in the management of AOSD is scarce, these drugs represent a major breakthrough in the management of patients with AOSD refractory to corticosteroids or conventional DMARDs or in patients presenting life-threatening manifestations. In this regard, TNF-α, IL-1, and IL-6 antagonists had been proved effective in patients with AOSD.
Abstract Chronic inflammatory rheumatic diseases (IRD), including rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis, are prevalent conditions worldwide, with a considerable burden ...on healthcare systems. They are associated with increased cardiovascular (CV) morbidity and mortality. In this review, we focused on the epidemiology, traditional CV risk factors, genetics, and the link between chronic inflammation, atherosclerosis, and CV disease. Remarkably, patients with IRD have higher vulnerability to atheromatous plaques. The risk of unstable plaques is higher in patients with rheumatoid arthritis than in controls. Active disease is a characteristic ascribed to vulnerability and rupture of plaques and a cause of thrombosis in IRD. Management of CV risk in patients with IRD includes optimal control of disease activity. CV risk stratification by applying risk charts is also essential. Imaging techniques might be useful to determine the actual CV risk of patients with IRD who are included in the category of intermediate or moderate CV risk.