Review Articles in 2009

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.

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.

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.

The use of high-resolution imaging techniques will lead to a better understanding of the relative contribution of the different hierarchical levels to bone competence. Such information could help improve predictions of fracture risk, clarify the pathophysiology of skeletal diseases, and define the response to therapy. This Review focuses on three-dimensional approaches to hierarchical biomechanical imaging in the study of microstructural and ultrastructural bone failure.

Mesenchymal stem cells (MSCs) are able to differentiate into chondrocytes, osteoblasts and adipocytes. As well as their potential use in tissue engineering, however, MSCs also potently modulate immune responses, exhibit healing capacities, improve angiogenesis and prevent fibrosis, at least partly by secreting several cytokines and growth factors.

Although major improvements have been made in the management of systemic lupus erythematosus, the numerous burdens associated with long-term disease have a significant impact both on individual patients and society as a whole.

The treatment strategy for a patient with rheumatoid arthritis who plans to conceive or is already pregnant must be tailored according to not only disease activity but also which drugs are compatible with pregnancy. The safety of various therapeutic agents during pregnancy is discussed in this Review, as well as issues of handling inadvertent exposure to potentially fetotoxic drugs and managing flares of disease activity during pregnancy.

Several cellular responses, in different cell types, are involved in the pathogenesis of rheumatoid arthritis. Common to many of these responses is signal transduction through tyrosine kinases. Evidence implicating certain tyrosine kinases in the pathogenesis of rheumatoid arthritis, and the potential to inhibit these kinases, is outlined in this Review.

In cases where symptoms of knee osteoarthritis persist despite conservative treatment, surgery can be offered to patients. The choice of procedure from the available options, which include arthroscopy, osteotomy and knee arthroplasty, is influenced by factors including the location and severity of joint damage, patient characteristics and risk factors.

The homeostatic processes of adipogenesis and osteoblastogenesis are tightly linked, as discussed in this Review. Research into the bone–fat network has led to the elucidation of pathways that could be pharmacologically targeted in an attempt to enhance bone mass and reduce osteoporotic fracture risk.

Type 17 T helper (T_H17 ) cells were first discovered in mice as a distinct population of T helper cells that produce interleukin-17. Since then, the origin of human T_H17 cells, the factors inducing their differentiation and the possible role these cells have in the pathogenesis of human rheumatologic disorders have been matter of intense debate.

Various rheumatic conditions are characterized by endothelial dysfunction and a proinflammatory state, both of which can lead to premature atherosclerosis. Circulating endothelial progenitor cells are involved in endothelial repair, but the number and function of these cells are affected in rheumatic diseases, as discussed in this Review.

Activated synovial fibroblasts have an important role in the destruction caused in rheumatoid arthritis. The aggressive phenotype of these cells is influenced by various epigenetic mechanisms, in particular DNA methylation. Improved understanding of these epigenetic alterations could inform the development of novel therapies for rheumatoid arthritis.

Genomic technologies are becoming increasingly accessible to clinical research laboratories. Gene-expression profiling is a powerful tool that can be used for the identification of biomarkers, with potential widespread clinical applications in rheumatic disease. These applications, together with an overview of the latest technologies for gene-expression profiling, are outlined in this Review.

Lupus mesenteric vasculitis is the main cause of acute abdominal pain in patients with acute gastrointestinal manifestations of systemic lupus erythematosus. Abdominal CT allows for early and accurate diagnosis of this painful and potentially life-threatening condition, which enables implementation of appropriate immunosuppressive therapy and avoidance of unnecessary surgical intervention.