Reviews & Analysis

Arachnodactyly–spidery fingers–is typical of patients with one of the heritable diseases of connective tissue. This Review highlights the differences and similarities amongst these diseases and serves as a diagnostic guide to these heritable diseases including Marfan syndrome, joint hypermobility syndrome, and Ehlers–Danlos syndrome.

Total hip and total knee replacements are common treatments for end-stage arthritis with the rates of these procedures projected to increase further over the coming decades. Currently, no evidence-based criteria exists to guide physicians in which patients to refer for these treatments meaning that there is a potential for bias in this decision-making process. Here, Lisa Mandl reviews common misperceptions among physicians regarding these procedures, and discusses data that should be considered by physicians during the referral process.

Wnt signalling has important roles in bone development, growth and homeostasis. Herein, the authors review our current understanding of Wnt signalling in rheumatoid arthritis, osteoarthritis and spondyloarthritis, and discuss the potential therapeutic targeting of the Wnt cascades in these diseases.

The contribution of epigenetic mechanisms, primarily comprising microRNAs and modifications of DNA and histones, to rheumatoid arthritis (RA) is increasingly recognized. In this article, the authors discuss the role of the epigenetic machinery in this disease, with a particular focus on the enzymes that regulate protein acetylation, and the therapeutic potential of targeting these factors in RA. The authors suggest that returning to the original, broader definition of epigenetics, comprising all nongenetic regulatory mechanisms, might improve our understanding of disease and facilitate the development of novel therapeutic strategies.

Undoubtedly, biologic agents have altered the landscape of therapeutic options for patients with rheumatoid arthritis (RA). Nevertheless, the choice can be bewildering, especially as several different molecules and pathways are the targets of approved and developmental therapies in RA. The authors of this Review provide a guide to navigate the current options and to understand how the picture is likely to evolve in the near future.

Biomarkers have the potential to improve all aspects of clinical practice, from diagnosis to monitoring of treatment effectiveness. In this Review, the authors use current and potential biomarkers from rheumatology and beyond to highlight the value of different types of biomarker in drug development and clinical decision making. Particular emphasis is placed on mechanistic biomarkers, which are rooted in disease pathogenesis and can provide an accurate reflection of disease activity.

Advances in our understanding of immune cell receptors and the development of biologic agents targeting them have revolutionized the treatment of rheumatoid arthritis (RA). Now, inhibitors of kinases integral to the signalling pathways downstream of these receptors have been added to the therapeutic armamentarium. This Review discusses the signalling pathways and small-molecule inhibitors of their component kinases that have already shown, or are predicted to show, promise in the treatment of RA.

Pharmacogenomic advances have increased understanding of allopurinol-associated severe cutaneous adverse reactions (SCARs), demonstrating that HLAB^*5801 is a strong risk factor for their development. In some populations, all patients with allopurinol-induced SCARs carry this allele. New treatment recommendations outline how this discovery should influence gout therapy, particularly the use of allopurinol.

The treat-to-target approach has been a major breakthrough in the treatment of rheumatoid arthritis. Although this strategy has been evaluated in many clinical studies, whether a high level of adherence is feasible in real-world clinical practice remains uncertain.

The presence of anti-drug antibodies (ADA) can result in the loss of response to anti-TNF biologic agents in patients with rheumatoid arthritis. In this article, van Schouwenburg et al. outline the limitations of current assays for ADA detection and discuss how studying the immune responses caused by the different anti-TNF biologic agents could lead to strategies to help reduce or prevent the development of ADA.

Drug development, underpinned by randomized controlled trials, has greatly advanced the the treatment of rheumatoid arthritis (RA). However, modern principles and goals of RA management raise new challenges and call into question the appropriateness of traditional trial designs. This Review discusses these designs and the associated challenges, and outlines opportunities that arise from innovative trial designs.

A rational approach to the management of rheumatoid arthritis (RA) begins with understanding the disease, development of which can be influenced by environmental, genetic and epigenetic factors. Genetic and epigenetic data in RA are revealing insights into pathogenesis and revitalizing the shared epitope hypothesis. These advances are discussed in this Review, alongside approaches to integrating the findings of genetic and functional studies.

Neridronate, an aminobisphosphonate, has shown promise in reducing the often extreme and intransigent pain of complex regional pain syndrome. Welcomed clinically, what can this finding tell us about the enigmatic mechanisms of bisphosphonates and of complex regional pain syndrome alike?

Evolving understanding of the role of helminths in the pathogenesis of autoimmunity has led to the development of novel therapeutic interventions that are showing promise in patients with immune-mediated diseases. Meanwhile, studies in animal models of arthritis suggest that these new products might also be applicable in autoimmune rheumatic disease.

A number of microRNAs have been implicated in the pathogenesis of various rheumatic diseases, and evidence in support of the therapeutic potential of microRNA-based strategies for these conditions is growing, as demonstrated by several new findings published in 2012.

Tissue engineering and regenerative medicine have advanced rapidly towards the development of therapeutic solutions for musculoskeletal disorders. In 2012, breakthroughs have been made in the guidance of adult stem cell homing, the tissue regenerative activity of stem-cell-derived extracellular matrix has been tested, and novel, mechanically superior biomaterials have been fabricated.

Semiquantitative MRI-based scoring of joint pathology is a powerful tool in osteoarthritis (OA) research, which provides valuable information on the natural history of the disease and can be used in outcome measures. Herein, the authors discuss approaches to semiquantitative MRI-based scoring of OA features and review the scoring systems currently available for whole-joint and feature-specific assessment of knee, hand, hip, spine and shoulder OA.

Developments in our knowledge of the aetiology and pathogenesis of rheumatoid arthritis continued apace in 2012, and several important new advances were reported in the therapy of this disease. Culminating in the approval of a new therapy in the USA, the year offered new insights for clinicians and fresh hope for patients.

In 2012, several new concepts emerged that widen our view of the regulation of bone mass in health and disease. Three key studies outline these discoveries, which affect our understanding of the skeletal system, particularly its physiological function and the changes it undergoes during inflammatory disease.

2012 has witnessed new developments in targeted therapies for osteoarthritis, and in ways to identify those patients who might benefit most from their application. Together, these advances could go some way to addressing the urgent need for disease-modifying treatments for this common disease.