Reviews & Analysis

Medications that inhibit gastric acid secretion are standard co-therapy with NSAIDs, but evidence is emerging of a link between prolonged use of these agents and an increased risk of hip fracture.

Clinical tests of the novel small-molecule inhibitor of p38α MAPK, VX-702, have resulted in an all-too-familiar outcome: modest clinical efficacy and transient inhibition of inflammatory markers. Why have p38α inhibitors failed, and what can we learn about the regulation of signal transduction pathways in inflammatory arthritis?

The degree to which the elevated risk of malignant lymphomas in patients with rheumatoid arthritis (RA) is related to disease activity or to therapy is uncertain. Evidence is mounting in support of a strategy of more-intensive cancer screening in these patients.

Clinical guidelines and recommendations, as well as clinicians and patients, consider non-pharmacological modalities to be the mainstay of treatment for osteoarthritis (OA). Despite this consensus in opinion, however, the evidence base for the non-pharmacological management of hand and hip OA continues to lag far behind that for knee OA, which suggests that more research is required to optimize the management of hand and hip OA.

Song and colleagues describe the diagnosis and treatment of a 50-year old man with pansclerotic morphea with immune-mediated bone-marrow failure and cytopenias. Although standard therapies for fibrotic skin disorders were ineffective, the patient responded to T-cell-targeted treatment with antithymocyte globulin.

Sensorineural hearing disorders are more common in patients with rheumatic disease than in the general population, so it is important that rheumatologists know how to diagnose and treat these comorbidities. In this Review, the categories of sensorineural hearing loss are introduced, and diagnostic and therapeutic approaches for these disorders are outlined.

Patients with Paget disease are often asymptomatic, but some experience considerable morbidity in the form of bone pain and skeletal deformity, as well as a variety of regional complications. Bisphosphonates are an effective treatment for Paget disease, but questions still need answering as to when and when not to treat symptomatic and asymptomatic patients with this potentially painful and deforming disease.

In April 2009, efalizumab was withdrawn from the market for the treatment of psoriasis after reports emerged of an association between long-term therapy and the development of progressive multifocal leukoencephalopathy (PML). This event highlights an urgent need for greater awareness and research into the screening, diagnosis and treatment of this potentially fatal disease in patients undergoing immunosuppressive therapy for chronic inflammatory disorders.

Molecules involved in developmental signaling pathways have emerged as therapeutic targets for various rheumatic diseases. New research sheds light on the consequences of interfering with these processes.

The choice of optimum second-line DMARDs for patients with rheumatoid arthritis is fraught with challenges. The implementation of evidence-based guidelines designed to inform clinicians' decisions requires careful consideration of several important issues.

As of May 1, 2009, PubMed listed approximately 30,000 citations on the topic of vitamin D in humans, highlighting the medical community's avid interest in this field. Two articles published in the Archives of Internal Medicine diverge with previous reports on the prevalence of hypovitaminosis D and the capability of vitamin D to reduce fractures.

Several high-profile institutions are now following the trend of limiting doctors' ties to industry by way of implementing stringent new guidelines. But do the recommendations go far enough?

This Case Study presents a 70-year-old woman who was administered etanercept to treat rheumatoid arthritis that was active, despite therapy with conventional DMARDs. During follow-up, the patient's symptoms improved but she developed weakness and numbness in her arms and legs. Investigations revealed a mass in her cervical spine, which was histopathology confirmed to be a benign meningioma.

New clinical guidelines incorporate the concept of absolute fracture risk, an important advance in the field of rheumatology. This Review article discusses the background, history and recent advances in the use of absolute fracture risk assessment in the management of patients with osteoporosis.

Since the 1970s, rheumatologists have increasingly reported seeing patients with milder onset of rheumatoid arthritis and a less-severe disease course than in preceding decades. Are these improvements attributable to earlier diagnosis, better therapeutic options, or simply a milder natural disease course? Uhlig and Kvien review the evidence for the perceived decrease in disease severity and discuss the potential reasons for this phenomenon.

In patients with rheumatoid arthritis, the benefits of tight control of inflammation to prevent or delay joint erosion are clear. Markers predictive of erosive disease enable physicians to identify those patients who would benefit most from aggressive therapy, thus avoiding unnecessary risks and costs associated with this intensive treatment approach. This Review discusses various prognostic factors as well as issues that confound their identification and application.

The risk of experiencing a fracture is lower in men than in women beyond the age of 50 years, but the burden of fractures is, nevertheless, substantial in men. This difference in fracture incidence is likely to be accounted for by differences in bone-related and fall-related factors, which are outlined, along with other data relating to the epidemiology, pathophysiology and treatment options for osteoporosis in men, in this Review.

A tripartite sensing apparatus, comprising Toll-like receptors, retinoid acid-inducible gene-I-like receptors and other cytosolic nucleic acid sensors, and nucleotide-binding and oligomerization domain-like receptors, has evolved to bring about an immediate but short-lived defense response to microbial pathogens and their products. The main components of these three systems and their function in detecting cellular danger are outlined in this article.

The signaling pathways regulating the closely linked processes of adipogenesis and osteoblastogenesis are controlled by numerous transcription factors. This article focuses on the role of peroxisome proliferator activated receptor γ in the promotion of adipogenesis, and the Wnt–β-catenin and noncanonical Wnt signaling pathways in the promotion of osteoblastogenesis, and the crosstalk between these pathways.

B-cell-directed therapies for autoimmune diseases have been the focus of extensive research during the past few years. In this Review, the authors discuss therapies that directly and indirectly target B cells. They outline clinical experience to date, mechanisms of action at the cellular level and possible issues of relevance to the efficacy and safety of these therapeutics.