Reviews & Analysis

This article provides an overview on the structure and function of the syndecan family of transmembrane proteoglycans. The authors discuss the regulation of these molecules and their roles in the developing joint as well as in cartilage breakdown and synovial inflammation.

Following a decade of substantial improvements in sensitivity and usability, MRI is increasingly used to assess primary outcomes of therapeutic trials in rheumatoid arthritis (RA). In the wake of an MRI-based evaluation of treatment efficacy, what lessons are emerging about the clinical value of this technique for patients with RA?

Early diagnosis of psoriatic arthritis will prevent joint damage and improve long-term patient outcome. For dermatologists and general practitioners, early recognition of the diverse musculoskeletal manifestations can prove problematic. Screening tools and biomarkers offer great promise—the recent description and initial validation of the EARP tool is an encouraging development.

Crosstalk between the skeletal and immune systems—especially immunomodulation of bone turnover, but increasingly also regulation of immune functions by bone cells—was recognized during research into arthritis and has evolved into the discipline of osteoimmunology. Hiroshi Takayanagi presents an update of advances in this area, focusing on the influences of T cells on bone remodelling, and relationships between osteoblasts and haematopoiesis.

Aberrant expression of microRNAs is associated with the pathogenesis of systemic lupus erythematosus (SLE). In this Review, Shen and colleagues discuss the potential of microRNAs to act as biomarkers for the diagnosis and assessment of patients with SLE, as well as the future therapeutic potential of targeting miRNAs in the management of patients with SLE.

Increasing evidence points towards the skeleton as having an endocrine role in humans. In this Review, DiGirolamo and colleagues introduce the concept of the skeleton as an endocrine organ, summarizing the evolution of skeletal endocrine networks and the role of the skeleton in phosphate and glucose homeostasis.

Despite their association with loss of bone mass and increased fracture risk, glucocorticoids have been an important component of rheumatoid arthritis therapy for more than 60 years. In this article, Ulrike Baschant and colleagues describe the tissue-specific, molecular and cellular mechanisms of glucocorticoid action, and suggest new criteria for selective glucocorticoid receptor agonists, which could have similar anti-inflammatory efficacy to traditional glucocorticoids without the adverse effects.

Vaccination for the prevention of herpes zoster with the attenuated live vaccine is currently not recommended for patients with rheumatic diseases while they are receiving biologic agents, but new evidence calls the validity of this guidance into question. Is it time to rethink the use of the herpes zoster vaccine in these patients?

Achievement of a state of inactive disease has become a realistic goal in juvenile dermatomyositis. The development of a standardized definition of inactive disease in this disorder is a critical step in measuring outcomes, and might now be a step closer.

Insulin resistance is closely associated with an increased risk of subclinical atherosclerosis in patients with rheumatoid arthritis (RA). Anti-TNF therapy reduces insulin resistance and improves insulin sensitivity in patients with severe RA. New findings have shown, however, that the efficacy of these agents in this regard is impaired by obesity.

In this Review, the authors summarize the substantial progress that has been made in understanding the pathophysiology of bone erosions and discuss the improvements in the diagnosis, monitoring and treatment of such lesions.

Noninvasive biomolecular imaging techniques, such as thermography, near-infrared imaging, PET and single photon emission CT (SPECT), can be used to detect the earliest biological and physiological changes that are associated with rheumatoid arthritis (RA). The authors describe these new imaging approaches, which could enable targeted intervention in early RA before the occurrence of irreversible joint damage.

In this Review, the authors discuss issues that surround the diagnosis and differential diagnosis of Behçet syndrome. Current approaches to managing patients with disorders of this complex group are also presented.

In the absence of definitive diagnostic tests, several schemes for the classification of paediatric vasculitis have been devised and periodically updated, but are these revisions necessary and useful?

Study of the efficacy of fracture prevention approaches has been neglected in men, in comparison with women. Guidelines from the Endocrine Society for the management of osteoporosis and fracture risk in men are thus welcome, but further research into fracture prevention in men is required.

In this Review, the authors summarize the latest findings on changes in effector T-cell homeostasis in autoimmune disease and discuss how mechanisms that normally regulate these cells are affected in the inflamed joints of patients with arthritis. The clinical implications of these findings are also described.

Determining the potential success of investigational therapies for rheumatoid arthritis early in the development process would enable better allocation of increasingly limited resources. Such 'go or no-go' decision-making could be improved by a method of analysing longitudinal clinical trial data to establish a threshold for success of a new drug.

The latest in a series of meta-analyses of trials assessing viscosupplementation for knee osteoarthritis is the first to raise concerns about its safety. Questions remain, however, regarding the methodological rigour with which the serious adverse events were analyzed, and the biological plausibility of the events reported.

Uric acid not only triggers inflammation in gout in its crystallized form, monosodium urate, but is also associated with comorbidities of the disease. New insights into the role of uric acid as a danger signal for both adaptive and innate immune responses could help to explain the pathogenesis of gout and point to potential new avenues of therapy for this and other sterile inflammatory diseases.

In this update on the genetics of hyperuricaemia and gout, the authors describe the associations between common genetic variants, serum uric acid levels and gout as well as the role of these genetic variants in gout pathogenesis. Pharmacogenetic associations betweenHLA-B^*5801and severe allopurinol-hypersensitivity reactions and the potential causal role of urate in cardiovascular disease are also discussed.