Review Articles in 2013

In this Review, the authors analyse the genetic loci associated with osteoarthritis to identify biological pathways that might be involved in the disease pathogenesis. In particular, they highlight the potential importance of certain regulators of skeletogenesis, endochondral ossification and gene transcription in this disease.

Nanotechnology, building on advances in nanoscience, has developed substantially over the past decade. In this Review, Cameron Brown outlines applications of nanotechnology that are advancing understanding in rheumatology and musculoskeletal research, including labelling, imaging and targeting techniques used to probe and manipulate cell behaviour. Nanoscale therapeutics might also enter the rheumatology clinic in future, but the potential for adverse events must first be explored; data accumulated in life-threatening illnesses will inform developments for chronic conditions.

Encouraging data from preclinical studies, and ongoing clinical trials, suggest that mesenchymal stem cells (MSCs) might provide the disease-modifying therapy that has long been lacking in osteoarthritis. If the potential of these multipotent cells is to be fully realized, subtleties such as minor phenotypic differences between specific MSC populations as well as the paracrine responses that transplanted MSCs elicit from joint-resident cells, must be better understood. MSC-related changes that occur in OA, the regenerative capacity of transplanted MSCs, and progress toward clinical use of such therapy are reviewed in this article.

In the past decade, knowledge of the pathogenesis of primary Sjögren's syndrome and the lymphomagenesis associated with this disease has advanced considerably. This Review summarizes our current understanding of these processes, highlighting the importance of crosstalk between the innate and adaptive immune systems.

Vaccinating children with underlying rheumatic diseases is important to reduce their risk of acquiring infectious diseases. These vaccines are safe to use in this patient group, with the exceptions of profoundly immunosuppressed pateints or those with malevonate kinase deficiency. Some vaccines also induce lower than normal immune responses in these children.

Prevention and recognition of mycobacterial disease is of increasing importance to the practicing rheumatologist. Tuberculosis remains a well-known problem for patients and clinicians wishing to use immunosuppressive therapies. Less well recognized, and yet perhaps more important to consider in this context, is nontuberculous mycobacterial disease. Epidemiological data and mechanistic explanations for the increased risk of mycobacterial infection in patients with RA are reviewed herein, and appropriate strategies to prevent and manage these comorbidities are outlined.

The population of elderly patients with rheumatoid arthritis (RA) is growing, primarily as a consequence of increasing life expectancies. In addition, processes linked to ageing of the immune system might directly contribute to development of this disease. This Review discusses the evidence supporting this hypothesis, as well as the challenges facing management of RA in elderly patients.

Despite having increased cardiovascular risk, patients with rheumatoid arthritis (RA) often have low serum cholesterol levels. In this Review, the authors discuss this putative 'lipid paradox', highlighting the relationships of inflammation and anti-inflammatory therapy with lipid profiles in RA.

Multiple genes have been associated with susceptibility to systemic lupus erythematosus (SLE), but how do they promote disease development? In this Review, the authors examine the roles of a selected set of genes in the pathogenesis of SLE, and discuss how epigenetic modifications and microRNAs can mediate pathogenic changes in gene expression.

Musculoskeletal ultrasonography is widely used for evaluating patients with RA and these imaging techniques can also allow the comparison of therapeutic agents, as well as monitoring patient response to treatment. Here, Ohrndorf and Backhaus describe the ultrasonographic features that can be used as predictive markers, and the ultrasonographic scores that can be used to reflect overall RA disease activity.

In this Review, Little and Hunter discuss the use of animal models in osteoarthritis (OA) research, focusing on their importance in understanding post-traumatic OA, the human form of the disease that the models most accurately reflect. The authors also outline the approach necessary for the successful translation of scientific data into clinically useable drugs.

As molecular complexes that promote inflammation, inflammasomes have been implicated in several autoimmune and autoinflammatory disorders, including cryopyrin-associated periodic syndromes and microcrystal-induced pathologies. Here, the authors discuss the roles of inflammasomes in these conditions, as well as their potential involvement in other rheumatic diseases, and consider therapeutic approaches to inhibit inflammasome activity.

Both the classical effects of vitamin D on bone and its other, nonclassical, effects, particularly those on the immune system, could be of relevance to rheumatic diseases; indeed vitamin D deficiency has been associated with such conditions in observational studies. The clinical importance of these findings, however, is unclear. This Review appraises the current evidence in this area, particularly in relation to whether vitamin D supplementation should be considered, or not, in approaches to the management of rheumatic disease.

Genetic factors have critical roles in primary paediatric osteoporosis, which occurs in otherwise healthy individuals in forms that include osteogenesis imperfecta. Secondary osteoporosis results from an underlying illness and is common in children with chronic systemic inflammation, neuromuscular disabilities, or who are receiving glucocorticoid treatment. Mäkitie discusses the occurrence and management of paediatric osteoporosis, with a focus on prevention of skeletal complications, and highlights the need to broaden treatment options.

In the era of targeted therapy, patients with rheumatic diseases have seen real results. But what about those with systemic sclerosis—where is the long-awaited antifibrotic drug? Disparate aspects of the pathogenesis are gradually being integrated into a cohesive model, and molecular targets that are shared with other diseases are also being defined. As this Review stresses, careful evaluation of new strategies, with a focus on learning fundamental lessons about the underlying biology, will be needed to translate novel approaches into actual clinical progress in this recalcitrant disease.

Biologic agents have been used successfully to treat rheumatoid arthritis, but are less effective in osteoarthritis. Chevalier et al. discuss the use of cytokine blockers, inhibitors of nitrogen oxide production, and growth factors to treat osteoarthritis—clinical trial data has been overwhelmingly negative but glimmers of hope still exist.

In this Review, the phenotypic and genetic markers for common musculoskeletal pain conditions are discussed. Furthermore, the authors propose a heuristic approach to evaluation of the different kinds of markers associated with these conditions, which could enable greater understanding of the underlying pathophysiological processes.

Patients with rheumatoid arthritis or ankylosing spondylitis can have disease-associated complications involving the spine. Cha and An discuss these cervical spine manifestations and how they should be managed, risks associated with inaction, potential complications of treatment, and indications for surgery. Whereas biologic agents are sufficient to slow progression of spinal pathology in many patients with rheumatoid arthritis, the authors recommend early surgical intervention in those who develop neurological deficits.

Pathogenic IgG autoantibodies have established roles in diseases including systemic lupus erythematosus and rheumatoid arthritis. Less familiar are the influences of naturally arising IgM autoantibodies, which enhance phagocytic clearance of apoptotic cells and have the capacity to block inflammatory responses induced by Toll-like receptor ligands and autoantibody-containing immune complexes. Intriguing data from animal models and clinical studies, suggesting that it might become possible to exploit these protective effects in the treatment of autoimmune rheumatic disease, are reviewed in this manuscript.

Cancer treatments can have severe adverse effects on bone health, and can thus increase the risk of fragility fractures both during therapy and in later life. This Review focuses on bone loss caused by breast cancer and prostate cancer treatments, and discusses lifestyle and pharmacological management strategies for reducing fracture risk in these patients.