Review Articles in 2010

Osteoarthritis (OA) is a disease of the whole joint, at the centre of which lies the interface between cartilage and bone. Altered transfer of mechanical stress across this boundary is thought to result from, and to exacerbate, OA, but molecular crosstalk was presumed to be minimal. Accumulating data challenge this assumption, and this Review explores the biology and pathology of the bone–cartilage functional unit.

Glucocorticoids are widely used anti-inflammatory and immunosuppressive drugs for rheumatoid arthritis. This Review outlines the indications for and benefits of glucocorticoids as co-therapy with other DMARDs, describes the adverse effects that are predominantly associated with high-dose or long-term therapy, and considers the impact of patients' and doctors' perceptions of glucocorticoid therapy on prescribing and adherence to treatment.

The etiology and pathogenesis of osteoarthritis (OA) are poorly understood, although proinflammatory cytokines are known to be critically implicated in the disease. In this Review, the authors discuss the current knowledge regarding the role of proinflammatory cytokines, particularly interleukin (IL) 1β, tumor necrosis factor and IL 6 in the pathophysiology of OA, and give an overview of efforts to develop adequate and specific anticytokine therapies.

The factors that trigger osteoarthritis (OA) have been difficult to identify, as the earliest molecular changes substantially precede clinical presentation of symptoms. Nevertheless, we are beginning to piece together the processes that occur in articular cartilage, and new tools promise to expedite completion of the puzzle. This Review outlines some of the events in early stages of OA development, focusing on the changes that occur in cartilage both before and after substantial loss of the tissue occurs.

Research into the effects of lower-extremity muscle weakness on osteoarthritis onset and progression has increased over the past decade, owing to its potential for modification using exercise training interventions. Similarly, afferent sensory dysfunction has also been suggested as an important yet modifiable risk factor for OA progression. In this Review, the authors provide an overview of these risk factors, and discuss the effectiveness of preventive or therapeutic neuromuscular and exercise training interventions.

Chondrocalcinosis, the calcification of cartilage, is caused by the deposition of calcium pyrophosphate crystals (CPPD). This Review describes regulators of pyrophosphate metabolism, and discusses the mutations and mechanisms that underlie familial CPPD.

Current therapeutic strategies for osteoarthritis (OA) are mostly palliative; modifying the structural progression of OA has, therefore, become a focus of drug development. This Review discusses the challenges involved in the discovery and development of disease-modifying OA drugs, and describes specific agents that have shown promise in phase II and III trials.

Severe osteoarthritis (OA) is the main cause of an increasing need for joint replacements and is, therefore, a large burden on both patients and the health-care sector. This Review discusses the genetic contribution to hip and knee OA and the authors suggest that identifying individuals at a high risk of OA with a combination of genetic markers might aid preventive and disease-management strategies.

Advances in genotyping technology, such as genome-wide association studies, have identified many robust genetic associations with systemic lupus erythematosus (SLE) in various ethnic groups. In this Review, the authors describe established and novel SLE-associated loci and discuss how genetic risk factors that are shared between autoimmune diseases can help to identify common disease pathways.

Dupuytren disease is a common disorder but its cause remains unknown and the treatment of its symptoms is often unsatisfactory. This article provides an overview of the current understanding of the genetics, pathogenesis and proposed etiology of this disease, as well as a discussion of current and emerging therapies.

Familial Mediterranean fever (FMF) is characterized by episodes of acute inflammation; however, in approximately 30% of patients with FMF inflammation persists even during the attack-free periods. In this Review, the authors discuss the markers and risk factors for persistent chronic inflammation in these patients, summarize the clinical outcomes of such inflammation, and suggest a new potential treatment strategy.

Advances in the field of MRI have given rise to sophisticated imaging modalities that allow the visualization of molecular pathologic processes that might precede overt structural damage seen on conventional imaging. In this Review, the authors summarize these advances and new directions in MRI in the context of synovial, bone and cartilage changes in rheumatoid arthritis.

Moving beyond the view of osteoarthritis as a disease of the cartilage, evidence is emerging that synovial inflammation is an important factor in the pathophysiology of the disease. In this article, Sellam and Berenbaum review that evidence, present various methods of assessing synovitis, and discuss the possibility of synovitis-targeted therapy for the treatment of osteoarthritis.

ANCA-associated vasculitides (AAV) involve inflammation and fibrinoid necrosis of the vessel wall. This Review highlights advances in our understanding of the cells and molecules that contribute to AAV pathogenesis and discusses new developments in the treatment of these diseases.

Psoriasis is only observed in humans; however, characteristics of the disease, such as prominent epidermal hyperplasia and a distinct inflammatory infiltrate, have been studied in mouse models of psoriasis. In this Review, the authors highlight the mouse models that have contributed to the discovery of novel disease-relevant pathways.

Many factors can influence the safety and effectiveness of biologic therapies for rheumatoid arthritis (RA) and, as outlined in this Review, the unique genetic, environmental and medical backgrounds of Japanese individuals could affect how they respond to biologic agents. This article describes the biologic agents used in Japan and the extensive post-marketing surveillance data for all patients with RA treated with biologic agents in Japan, which include the drug-related adverse events that have been documented.

Knowledge of the role of regulatory B (B_REG) cells in immune suppression and autoimmunity has improved. In this Review, the authors describe the advances in the study of B_REG cells, detailing the known B_REG cell subsets and the ontogeny and development of these cells. The authors also highlight the role of B_REGcells in human health and disease and their potential use as a therapy for a wide range of rheumatic diseases.

Cyclo-oxygenase (COX) inhibitors relieve musculoskeletal pain by blocking the activity of COX enzymes that regulate prostaglandin production. In this Review, the authors discuss the pharmacokinetics of widely used COX inhibitors and suggest strategies to optimize their analgesic effects and minimize adverse drug reactions.

Regulatory T (T_REG) cells, which function as suppressors of autoimmune responses, are defective in patients with rheumatoid arthritis (RA). In this article, the authors describe the interplay between T_REG cells and inflammation in the context of RA, and how a subset of highly potent but unstable T_REGcells seems to be induced following tumor necrosis factor blockade.

Biologic agents are emerging as an important treatment for juvenile idiopathic arthritis (JIA), but the long-term safety of these therapies is a major concern and currently not completely understood. This Review examines available data for the safety of biologic therapies for JIA and details the serious adverse events associated with each agent as well as outlining the safety issues that need further study.