Reviews & Analysis

Both systemic and local biomechanical factors contribute to joint degeneration in osteoarthritis, and diverse molecular mechanisms of the disease pathogenesis are being uncovered. Can mechanism-based treatments be developed for patients with this disease, as has happened with rheumatoid arthritis, and what are the challenges in drug development?

Nonpharmacological treatments cannot be assessed according to the same standards used for pharmacological treatments. This Review gives guidance on trial designs that address specific methodological issues encountered in assessment of nonpharmacological treatments, and on interpretation of data from such trials.

The risk of cardiovascular disease is increased in patients with rheumatoid arthritis, as discussed in this Review. Joan M Bathon and colleagues outline some preliminary recommendations for how these complications can be prevented and managed by aggressive control of both synovitis and conventional cardiovascular risk factors.

Chronic back pain has a huge impact on health-care systems and governments globally, being responsible for millions of days of lost work and disability. In this Viewpoint, Dr Hadler discusses how improved patient management and workplace policies can help reduce the escalating costs that are associated with this condition.

MRI shows great promise as a scoring system for spinal inflammation in ankylosing spondylitis. This Viewpoint discusses the progress in the development of MRI scoring methods and the prospective use of MRI as a tool to evaluate disease activity in patients with ankylosing spondylitis.

Despite extensive research, the etiopathogenesis of primary Sjögren's syndrome is not well understood. In this article, the hypothesis that activation of the type I interferon system contributes to the disease process is outlined and potential new therapeutic targets from this system for Sjögren's syndrome are discussed.

Paget's disease of bone, which is the second most common metabolic bone disorder and is characterized by focal increases in bone turnover, has a strong genetic component. As discussed in this Review, mutations in four genes have been described that cause Paget's disease of bone or related disorders, and all affect the receptor activator of nuclear factor κB signaling pathway.

The secretory functions of the exocrine glands are impaired in patients with Sjögren's syndrome, resulting in symptoms of dry eyes and dry mouth. This Review discusses the currently available treatments for the glandular and extraglandular manifestations of this chronic autoimmune disorder, and describes potential future therapies.

There have been many exciting advances in tissue engineering. This Viewpoint discusses the future application of this technology in the chronic rheumatic diseases, focusing on the advantages of methods of cartilage regeneration, such as scaffolds, gels, cell-seeding, fibers or cell cultures.

The widespread use of screening for circulating anti-neutrophil cytoplasmic autoantibodies (ANCA) in the diagnosis of ANCA-associated vasculitis has resulted in an increased occurrence of false-positive results and greater difficulty in the interpretation of such test results. Therefore, a rational strategy for ANCA testing is needed. The main problems with ANCA testing are discussed in this Viewpoint and some practical guidelines are given.

Tumor necrosis factor is a key cytokine in the pathogenesis of ankylosing spondylitis. As discussed in this Review, data from randomized controlled trials show that anti-tumor-necrosis-factor agents can control symptoms effectively and possibly prevent the progression of this chronic inflammatory disorder.

Advances in our understanding of the signaling pathways involved in the pathogenesis of polymyositis, dermatomyositis and inclusion-body myositis offer promise for the development of future therapies for these inflammatory myopathies, as discussed in this Review.

In this Review, Cornelia Weyand and Jörg Goronzy introduce the key role that T cells have in the pathogenesis of rheumatoid arthritis and discuss the development and application of T-cell-targeted therapies for this disease, focusing on approaches that block T-cell co-stimulation.

Although effective at inducing and maintaining remission in the majority of patients with Wegener's granulomatosis, agents such as cyclophosphamide and high-dose glucocorticoids are associated with severe toxic effects. In this Review, Peter Wung and John Stone discuss the progress that is being made in the search for alternative treatments for this common form of systemic vasculitis.

Evidence-based medicine and, primarily, data from randomized controlled clinical trials are continually regarded as the only valid sources for all clinical knowledge. This Viewpoint discusses the merits of 'practice-based evidence' and how this important information is currently undervalued in the clinical community.

There has been significant progress in the development of biological markers to assess joint and tissue damage in osteoarthritis. In this Viewpoint, Patrick Garnero discusses the developments in this field and how they will affect the future management of patients with osteoarthritis.

Currently available therapies for systemic lupus erythematosus are limited by side effects and poor response rates. A number of large-scale, double-blind, randomized, controlled trials assessing new treatments for this disease commenced in 2005, which, as discussed in this Review, suggests that we are about to enter a new era for the management of systemic lupus erythematosus.

Although bacterial infections are implicated in the pathogenesis of reactive arthritis, the role of pathogens in the development of other spondyloarthropathies is unresolved. In this Review, the natural history of infection-triggered arthritis, the mechanisms of disease development, and the potential for antibiotic therapy to modify the course of the disease are discussed.