Review Articles in 2013

Nestled at the interface of rheumatology—which tackles biochemical modulation of joint homeostasis—and orthopaedics, with its focus on mechanical joint homeostasis, is the burgeoning field of cartilage tissue structure-modifying therapies. Besides halting damage, though, is actual repair of cartilage clinically possible? This Review is a comprehensive guide to the extensive developmental progress, both made and that remains to come, in regenerative medicine for degenerative joint disease.

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.

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.

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.

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.