Best Practice & Research Clinical Rheumatology RSS feed: Current Issue. Evidence-based updates of best clinical practice across the spectrum of musculoskeletal conditions Best Practice and Research Clinical Rheumatology keeps the clinician or trainee informed of the latest developments and current recommended practice in the rapidly advancing fields of musculoskeletal conditions and science. The series provides a continuous update of current clinical practice. It is a topical serial publication that covers the spectrum of musculoskeletal conditions in a 4-year cycle. Each topic-based issue contains around 200 pages of practical, evidence-based review articles, which integrate the results from the latest original research with current clinical practice and thinking to provide a continuous update. Each issue follows a problem-orientated approach that focuses on the key questions to be addressed, clearly defining what is known and not known. The review articles seek to address the clinical issues of diagnosis, treatment and patient management. Management is described in practical terms so that it can be applied to the individual patient. The serial is aimed at the physician in both practice and training. The Best Practice and Research Clinical Rheumatology series provides up-to-date and expert information and opinion by drawing on Guest Editors and authors renowned for their expertise. This ongoing review of topics makes the serial ideally suited to supporting everyday clinical practice, for training needs as well as for maintaining knowledge and competency. Volume 22 (Volume 2008) 1. Connective tissue diseases M. Matucci-Cerinic & D. Furst 2. Musculoskeletal science T. Pap & U. Muller-Ladner 3. How to manage chronic musculoskeletal conditions - the principles P. Brooks & P. Conaghan 4. Miscellanous inflammatory musculoskeletal conditions J. Sibilia & H. Zeidler 5. Musculoskeletal conditions in the developing world G. Mody & R. Handa 6. Imaging in musculoskeletal conditions M. Cimmino and W. Grassi Volume 23 (2009) 1. Early rheumatoid arthritis 2. Vasculitis 3. How to do - practical procedures 4. Back pain 5. Systemic lupus erythematosus 6. Osteoporosis Volume 24 (2010) 1. Osteoarthritis 2. Paediatric rheumatology 3. How to manage chronic musculoskeletal conditions - a systematic approach to specific problems 4. Pharmacotherapy 5. Spondylo-arthropathies 6. Prevention / epidemiology This free sample chapter is being provided to demonstrate the Journal's approach to topics across the spectrum of musculoskeletal conditions. http://www.bprclinrheum.com/?rss=yesElsevier Inc.en © 2011 Published by Elsevier Inc. All rights reserved. Best Practice & Research Clinical Rheumatology1521-6942256December 2011 © 2011 Published by Elsevier Inc. All rights reserved. healthpermissions@elsevier.comhttp://www.bprclinrheum.com/article/PIIS152169421100177X/abstract?rss=yesEditorial Board/Aims and Scope10.1016/S1521-6942(11)00177-XBest Practice & Research Clinical Rheumatology 25, 6 (2011)2011-12-01Best Practice & Research Clinical Rheumatology2011-12-01256S1521-6942(11)X0008-6iiiiiihttp://www.bprclinrheum.com/article/PIIS1521694211001628/abstract?rss=yesDiseases of the musculoskeletal system, as a group, are among those that affect the largest segments of the population and carry the highest cost to society; at the same time, the individual suffers for extended times – days, weeks or years. In some cases, mechanisms of disease leading to tissue injury are becoming elucidated, with osteoporosis as one example, leading to rapid development of new therapies for specific intervention in the disease process by targeting triggering events and/or signalling pathways. In other diseases such as rheumatoid arthritis, the detailed understanding of key mechanisms is still limited. However, as several pathways of the immunoinflammatory response are activated, they have opened up for testing compounds inhibiting various of these aspects and, indeed, several efficacious biological compounds have meanwhile been licensed, whereby a major breakthrough was achieved by the introduction of inhibitors of tumour necrosis factor (TNF)-α activity in rheumatoid arthritis, followed by other biological compounds that target other cytokines or specific cells or cellular functions. In addition, more targeted therapies are expected and needed; yet current ones do not help all patients. Moreover, many of the therapies effective in rheumatoid arthritis have also proven their value in treating other chronic inflammatory diseases, such as psoriatic arthritis and axial spondyloarthritis.PrefaceDick Heinegård, Josef S. Smolen10.1016/j.berh.2011.11.011Best Practice & Research Clinical Rheumatology 25, 6 (2011)2011-12-01Best Practice & Research Clinical Rheumatology2011-12-01256S1521-6942(11)X0008-6749750http://www.bprclinrheum.com/article/PIIS1521694211001616/abstract?rss=yesArticular cartilage is a uniquely ordered tissue that is designed to resist compression and redistribute load, but is poorly equipped for self-repair. The chondrocyte is the only resident cell type, responsible for maintaining a specialised and extensive matrix that is avascular and lacks innervation. These attributes, as well as the slow turnover rate of aggrecan and type II collagen in mature articular cartilage, present a considerable challenge to the tissue engineer. Similarly, those attempting to halt the progression of cartilage erosion must contend with these unusual characteristics. This review explores the gaps in our knowledge of cartilage biology and pathology, including what is known about the relative contribution of collagenases and aggrecanases to cartilage degradation, the need to regulate the chondrocytic phenotype and the putative role of chondrocyte hypertrophy in the pathogenesis of degenerative and rheumatic joint disease. Recent advances in cartilage tissue engineering are also reviewed.Emerging Frontiers in cartilage and chondrocyte biologyAmanda J. Fosang, Frank Beier10.1016/j.berh.2011.11.010Best Practice & Research Clinical Rheumatology 25, 6 (2011)2011-12-01Best Practice & Research Clinical Rheumatology2011-12-01256S1521-6942(11)X0008-6751766http://www.bprclinrheum.com/article/PIIS1521694211001689/abstract?rss=yesRheumatoid arthritis is a systemic disease in which an autoimmune response translates primarily into joint inflammation with attendant joint destruction. While evidence implicates both the adaptive and innate immune system in rheumatoid synovitis, several lines of evidence now support the concept that the synovial tissue itself actively participates in the destructive inflammatory processes of arthritis. Specifically, the resident mesenchymal cells, the fibroblast-like synoviocytes (FLSs), frame a synovial microenvironment that responds to, augments and perpetuates the inflammatory process. Moreover, the FLSs have been recognised as the dominant cells mediating joint destruction. The identification of cadherin-11 expression on FLS provided an opportunity to unravel molecular mechanisms by which these resident mesenchymal cells govern processes that result in destructive synovitis in the context of systemic autoimmune disease. Herein, we discuss the unfolding biology of the synovial cadherin with its implications for the synovial pathology in arthritis, especially rheumatoid arthritis.The synovium as a privileged site in rheumatoid arthritis: Cadherin-11 as a dominant player in synovial pathologyHans P. Kiener, Thomas Karonitsch10.1016/j.berh.2011.11.012Best Practice & Research Clinical Rheumatology 25, 6 (2011)2011-12-01Best Practice & Research Clinical Rheumatology2011-12-01256S1521-6942(11)X0008-6767777http://www.bprclinrheum.com/article/PIIS1521694211001604/abstract?rss=yesRheumatologists have largely conceptualised joint disease in inflammatory and degenerative arthritis in terms of bone, cartilage and the synovial lining, but have tended to overlook other integral components of the joints which are attached close to joint margins. We discuss these structures under the umbrella term of ‘appendages’. These structures include ligaments, tendons, entheses or joint insertions, regional fibrocartilages, bursae and other peri-articular joint structures including fat pads and nails. In this review, we highlight how these structures play key pathophysiological roles in inflammatory arthritis and we emphasise how an understanding of these structures is collectively important for both clinical practice and future rheumatological research.Joint appendages – the structures which have historically been overlooked in arthritis research and therapy developmentZoe Ash, Dennis McGonagle10.1016/j.berh.2011.11.009Best Practice & Research Clinical Rheumatology 25, 6 (2011)2011-12-01Best Practice & Research Clinical Rheumatology2011-12-01256S1521-6942(11)X0008-6779784http://www.bprclinrheum.com/article/PIIS1521694211001562/abstract?rss=yesRheumatic diseases comprise a wide spectrum of different conditions. Some are caused by disturbances of the adaptive immune system, while defects in innate immune responses have been identified for others. In between are a variety of multifactorial diseases for which the evidence for a causative involvement of the adaptive immune system is still controversial. In these cases, availability of novel drugs that target key players of the adaptive immune system have improved our understanding of the relevance of adaptive immunity to the disease process, but it has also generated unprecedented findings.Rheumatoid arthritis (RA) is a prototypic example of a disease in which the relative contribution of adaptive immunity to disease pathogenesis is incompletely understood. Although numerous markers have been identified that reflect an activated adaptive immune system, several caveats render interpretation of these findings difficult. For one, the very early immune responses initiating disease are likely to take place before an individual is identified as a patient, and are thus difficult to study in the human. Furthermore, increasing evidence points to pathogenetically distinct subgroups within the clinical diagnosis RA, offering the possibility that adaptive immune responses might be relevant to one subgroup but not the other. In addition, many indications for an adaptive immune system involvement are based on associations for which the underlying mechanism is often unknown. Finally, therapeutic interventions targeting the adaptive immune system have generated heterogeneous results.The present review addresses these issues by placing adaptive immune responses in the context of rheumatic diseases, and by reviewing the evidence for a contribution of adaptive immunity to RA.Adaptive immunity in rheumatic diseases – Bystander or pathogenic player?Hans Ulrich Scherer, Gerd-Rüdiger Burmester10.1016/j.berh.2011.11.005Best Practice & Research Clinical Rheumatology 25, 6 (2011)2011-12-01Best Practice & Research Clinical Rheumatology2011-12-01256S1521-6942(11)X0008-6785800http://www.bprclinrheum.com/article/PIIS1521694211001598/abstract?rss=yesThe pathogenesis of osteoarthritis (OA) appears to be the result of a complex interplay between mechanical, cellular and biochemical forces. Obesity is the strongest risk factor for disease onset in the knee, and mechanical factors dominate the risk for disease progression. OA is a highly prevalent and disabling disease. The current pre-eminent focus in OA research and clinical practice is on persons with established radiographic symptomatic disease. This is the very end-stage of disease genesis, and modern therapies hence are largely palliative. In an effort to mitigate the rising tide of increasing OA prevalence and disease impact, we need to focus more on preventing the onset of disease and modifying the structural progression of OA. Greater therapeutic attention to the important role of mechanical factors, joint injury and obesity in OA etiopathogenesis, is required if we are to find ways of reducing the public health impact of this condition.OsteoarthritisDavid J. Hunter10.1016/j.berh.2011.11.008Best Practice & Research Clinical Rheumatology 25, 6 (2011)2011-12-01Best Practice & Research Clinical Rheumatology2011-12-01256S1521-6942(11)X0008-6801814http://www.bprclinrheum.com/article/PIIS1521694211001690/abstract?rss=yesBiomechanical factors play an important role in the health of diarthrodial joints. Altered joint loading – associated to obesity, malalignment, trauma or joint instability – is a critical risk factor for joint degeneration, whereas exercise and weight loss have generally been shown to promote beneficial effects for osteoarthritic joints. The mechanisms by which mechanical stress alters the physiology or pathophysiology of articular cartilage or other joint tissues likely involve complex interactions with genetic and molecular influences, particularly local or systemic inflammation secondary to injury or obesity. Chondrocytes perceive physical signals from their environment using a variety of mechanisms, including ion channels, integrin-mediated connections to the extracellular matrix that involve membrane, cytoskeletal and intracellular deformation. An improved understanding of the biophysical and molecular pathways involved in chondrocyte mechanotransduction can provide insight into the development of novel therapeutic approaches for osteoarthritis.Biomechanical factors in osteoarthritisFarshid Guilak10.1016/j.berh.2011.11.013Best Practice & Research Clinical Rheumatology 25, 6 (2011)2011-12-01Best Practice & Research Clinical Rheumatology2011-12-01256S1521-6942(11)X0008-6815823http://www.bprclinrheum.com/article/PIIS1521694211001574/abstract?rss=yesThe most important clinical features of the spondyloarthritides (SpA) are not only inflammatory back pain (IBP) but also peripheral (enthesitis) and extra-articular symptoms. For clinical purposes, two forms related to the predominant clinical manifestation – axial and peripheral SpA – and five subgroups– ankylosing spondylitis (AS), SpA associated with psoriasis and inflammatory bowel disease (IBD), reactive arthritis and undifferentiated SpA – are differentiated. Axial SpA including AS is the most frequent subtype of SpA, followed by psoriatic arthritis and undifferentiated SpA, while reactive arthritis and IBD-related SpA are less frequent. The prevalence of SpA has been shown to be similar to rheumatoid arthritis. The outcome of the disease is influenced by the degree of disease activity over time, which is mainly related not only to inflammation but also on the structural damage (new bone formation) that occurs over time. Treatment options for patients with SpA have been limited for decades. Non-steroidal anti-inflammatory agents are currently considered first choice, since they have shown good amelioration of symptoms in SpA patients especially when suffering by the typical symptom of IBP. Furthermore, there is a clear role for regular physiotherapy in AS to prevent loss of spinal mobility. For patients who have insufficiently responded to conventional therapies, four anti-tumour necrosis factor (TNF) agents are available and are approved for the treatment of patients with active AS: infliximab, etanercept, adalimumab and golimumab. As far as it stands now, TNF blockers seem to have no influence on new bone formation in AS.SpondyloarthritidesXenofon Baraliakos, Juergen Braun10.1016/j.berh.2011.11.006Best Practice & Research Clinical Rheumatology 25, 6 (2011)2011-12-01Best Practice & Research Clinical Rheumatology2011-12-01256S1521-6942(11)X0008-6825842http://www.bprclinrheum.com/article/PIIS1521694211001586/abstract?rss=yesSystemic sclerosis (SSc) is a multisystemic fibrotic disorder that affects the skin and internal organs. Despite an improved outcome probably reflecting a better management of disease complications, morbidity and mortality remain higher than those of patients with other connective tissue diseases. SSc is still considered incurable; however, during recent years, intensive research activities have deepened the understanding of pathogenic mechanisms and have led to the identification of cellular and molecular anti-fibrotic targets. This review article will discuss potential future targeted therapeutic options based on data from in vitro studies, experimental models of fibrosis and first human trials with focus on scleroderma skin and lung fibrosis.Emerging targeted therapies in scleroderma lung and skin fibrosisBritta Maurer, Oliver Distler10.1016/j.berh.2011.11.007Best Practice & Research Clinical Rheumatology 25, 6 (2011)2011-12-01Best Practice & Research Clinical Rheumatology2011-12-01256S1521-6942(11)X0008-6843858http://www.bprclinrheum.com/article/PIIS1521694211001550/abstract?rss=yesThe need for improved analytical techniques in the study of slow, degenerative diseases such as rheumatoid arthritis and osteoarthritis has driven major efforts aimed at identifying biochemical markers of pathological processes in both diseases. A series of novel biochemical markers has surfaced and their careful validation has become a critical requirement for further use in clinical research.This report aims at providing a critical review of biochemical markers applied in clinical research of joint diseases, in particular those markers reflecting the turnover of cartilage tissue.Molecular serum and urine marker repertoire supporting clinical research on joint diseasesPer Qvist, Anne-Christine Bay-Jensen, Claus Christiansen, Bodil Cecilie Sondergaard, Morten A. Karsdal10.1016/j.berh.2011.11.004Best Practice & Research Clinical Rheumatology 25, 6 (2011)2011-12-01Best Practice & Research Clinical Rheumatology2011-12-01256S1521-6942(11)X0008-6859872http://www.bprclinrheum.com/article/PIIS1521694211001549/abstract?rss=yesThe approval – several years ago – of the first tumour necrosis factor-α (TNF-α) inhibitor for the management of rheumatoid arthritis launched a new era in the therapeutics of rheumatology. Since then an almost cataclysmic discovery of new treatment targets and corresponding biologic agents ensued. Nowadays, the rheumatologist and the rheumatologic patient have the luxury of several immune modulators available to successfully treat the majority of patients with RA or other inflammatory arthritides and conditions.In this review we focus on a discussion of the approved immune modulators/biologic agents available for the treatment of rheumatoid arthritis. We also present an overview of agents under development. For the immune modulators discussed, we describe their mechanism of action and summarise initial data and recent updates on efficacy and safety.Immune modulation of rheumatoid arthritisDimitrios A. Pappas, Laura Geraldino-Pardilla, Joan M. Bathon10.1016/j.berh.2011.11.003Best Practice & Research Clinical Rheumatology 25, 6 (2011)2011-12-01Best Practice & Research Clinical Rheumatology2011-12-01256S1521-6942(11)X0008-6873889http://www.bprclinrheum.com/article/PIIS1521694211001537/abstract?rss=yesGlucocorticoids remain part of the treatment strategy in many rheumatic diseases, because of their anti-inflammatory and immunosuppressive actions. Unfortunately, their clinically desired effects are linked to adverse effects, especially at higher dosages and longer duration of treatment. In this review, we describe new insights into the mechanisms of anti-inflammatory glucocorticoid actions and provide an update on recent approaches to improve the risk/benefit ratio of glucocorticoid therapy. Improved knowledge of the immunomodulatory role of endogenous glucocorticoids has evolved, and we report on the therapeutic potential of targeting glucocorticoid pre-receptor metabolism for metabolic and inflammatory diseases.GlucocorticoidsCornelia M. Spies, Cindy Strehl, Marlies C. van der Goes, Johannes W.J. Bijlsma, Frank Buttgereit10.1016/j.berh.2011.11.002Best Practice & Research Clinical Rheumatology 25, 6 (2011)2011-12-01Best Practice & Research Clinical Rheumatology2011-12-01256S1521-6942(11)X0008-6891900http://www.bprclinrheum.com/article/PIIS1521694211001811/abstract?rss=yesIndex10.1016/S1521-6942(11)00181-1Best Practice & Research Clinical Rheumatology 25, 6 (2011)2011-12-01Best Practice & Research Clinical Rheumatology2011-12-01256S1521-6942(11)X0008-6II