Reviews & Analysis

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.

Rapid progress is being made in the field of rheumatology. Nevertheless, disappointingly, the limited resources of the paediatric rheumatology community are being expended on the publication of consensus guidelines that represent fossilization of old ideas rather than real innovation that leads to the improved care of children.

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.

The American College of Rheumatology recently published a list of five strategies (comprising four diagnostic procedures and one therapeutic approach) that they consider to be often unnecessary and thus potentially wasteful. By itself this list is useful, but finding a way to reduce wasteful strategies will be a challenge.

Current classification criteria for rheumatoid arthritis allow its classification on the basis of the presence of erosions, in the absence of other indicators. Nevertheless, definition or quantitation of erosions was lacking. A European task force has now addressed this issue by analysing radiographic erosions in two cohorts of patients with early disease.

Bisphosphonates are the mainstay of treatment for osteoporosis, but uncertainties exist regarding their long-term use. The identification of patients who will benefit from continuing therapy is of primary clinical importance and a subject of current research. Risk factors for fractures are helping to improve decision making, but unanswered questions remain.

The results of a recent randomized, controlled study suggest than intra-articular injection of autologous stem cells collected from peripheral blood might improve the outcome of surgical approaches to regeneration of articular cartilage after injury. However, questions remain regarding the clinical benefit and feasibility of such an approach.

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 Lyme disease endemic areas, a noninvasive clinical prediction model to distinguish septic arthritis from Lyme arthritis would be useful, especially in children. A new study suggests that in highly selected patients, such prediction might be possible. But failure to recognize even a few cases of septic arthritis could have devastating consequences.

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.

Nestled at the interface of rheumatology—which tackles biochemical modulation of joint homeostasis—and orthopaedics, with its focus on mechanical joint homeostasis, is the burgeoning field of cartilage tissue structure-modifying therapies. Besides halting damage, though, is actual repair of cartilage clinically possible? This Review is a comprehensive guide to the extensive developmental progress, both made and that remains to come, in regenerative medicine for degenerative joint disease.

It is never too early to tackle arthritis. Currently, classification of rheumatoid arthritis is based on the clinical assessment of synovitis. The question is: should we consider 'clinical synovitis' the gold standard for clinical decision making, or should we try something more?

Myositis results from the combined activities of immune-specific and muscle-specific cell types. Immune muscle precursors could have a pivotal role, as they stimulate inflammation and the generation of autoantigens. Tournadre and Miossec explain this phenomenon.