Bone mineral density (BMD) testing is used to diagnose osteoporosis, assess fracture risk and monitor changes in BMD over time. A variety of devices and technologies are used to measure BMD or other surrogate markers of bone strength. Measurements obtained with these devices are often reported according to different proprietary standards, and the comparability of values obtained with different instruments is often poor. In addition, there is a high degree of variability in the skills of the technologists performing the tests and the clinicians interpreting the results. Heterogeneity in the guidelines for using BMD measurements together with poor-quality BMD testing and reporting can result in inappropriate clinical decisions, causing unnecessary worry and expense for the patient and possible harm due to unnecessary treatment or treatment being withheld. This Review describes and discusses the mistakes commonly made in BMD testing, and emphasizes the importance of maintaining high-quality standards in order to optimize patient management.

To study the HRQOL in veterans with prevalent total knee arthroplasty (TKA) or total hip arthroplasty (THA) and compare them with age- and gender-matched US population and control veteran population without these procedures.

To determine whether osteopontin (OPN) is increased in patients with AS and to investigate its relationship to inflammatory disease activity and bone remodelling process.

Biomechanical factors have a critical role in the onset and progression of osteoarthritis (OA). A recent carefully designed, randomized, controlled trial by Rodrigues and colleagues examined the use of an 8 mm medial-wedge insole for the management of lateral compartment knee OA associated with a valgus deformity. In this study the use of a wedged insole, together with ankle straps to provide ankle stability, was associated with substantial improvements in pain and functional status compared with a control, neutral insole; however, the trial sample size was small. Previous studies on lateral-wedge insoles for medial compartment knee OA have had conflicting results. Until larger, more-definitive trials are conducted, it would be reasonable for clinicians to provisionally recommend medial-wedge insoles for patients with lateral knee OA and a valgus deformity.

Poor sleep is associated with chronic widespread pain (CWP). Conversely, good-quality sleep may play a role in the resolution of pain symptoms. Sleep is a multidimensional construct, comprising a number of diverse components. The aims of the current study were to examine the hypotheses that: (i) good sleep quality would predict the resolution of CWP, (ii) restorative sleep would predict the resolution of CWP and (iii) that these relationships would be independent of confounding psychological factors.

Although neither lung biopsy nor bronchoalveolar lavage (BAL) is recommended for routine clinical use in patients with SSc, studies employing lung biopsy material and BAL fluid (BALF) have provided insight into the pathogenesis of scleroderma-associated interstitial lung disease (SSc-ILD). Most often, SSc-ILD is classified as a non-specific interstitial pneumonia, with abundant myofibroblasts and evidence of both epithelial cell and endothelial cell injury. Recently, SSc-ILD fibroblasts have been shown to express reduced levels of the caveolin-1 protein which, in turn, may lead to activation of the signalling molecules associated with increased collagen production and overexpression of alpha-smooth muscle cell actin (alpha-SMA). BALF often contains increased numbers of inflammatory cells as well as myofibroblasts expressing alpha-SMA. Analysis of BALF suggests an imbalance between pro-fibrotic and anti-fibrotic factors, e.g. an overabundance of TGF-beta, connective tissue growth factor (CTGF), PDGF, leucotriene B4, etc. and in some cases a deficiency of hepatocyte growth factor, 15-hydroxyeicosatetraenoic acid (15-HETE), lipoxin A, etc. Until the pathogenesis is fully understood, lung biopsy and BAL will remain useful research tools to better understand the inflammatory and fibrosing processes that underlie SSc-ILD.

Scleroderma is clinically heterogeneous and a variety of plausible mechanisms of disease have been hypothesized. Recent years have witnessed a significant improvement in overall survival although all of the gains in management have been therapies for specific organ involvement, e.g. renal crisis and pulmonary arterial hypertension. Future studies will rely on improved clinical science, which involves structured validation of proposed measures of outcome; development of a combined response index; and further refinement of specific subsets of disease expression. Immunoablation with stem cell reconstitution is an example of aggressive therapy chosen as appropriate for a particularly severe disease subset and in whom the pilot data are encouraging. Good science and clinical ethics force continued consideration of equipoise between risk and benefit.

The University of California at Davis 200 and 206 (UCD-200/206) lines of chickens have proven to be the animal model that best reflects the situation in human SSc. We have demonstrated a misbalance of pro-fibrotic (TGF-beta1) and anti-fibrotic (TGF-beta2 and -beta3) TGF-beta isoforms as a possible cause for fibrotic alterations in this model. This opens new avenues for diagnosis and therapy for this still intractable condition.

SSc can be associated with a high morbidity and mortality. Due to the complexity and heterogeneity of the disease, a composite response measure that will capture differing organ involvements and patient-reported outcomes is desirable. Recently, with participation of the Scleroderma Clinical Trial Consortium, a standardized core set of items were proposed for SSc clinical trials using a structured Delphi exercise. The Delphi exercise identified 11 domains relevant to SSc clinical trials. Currently, efforts are under way to develop a combined response index for clinical trials in diffuse cutaneous SSc.

Vascular abnormalities are a major component of SSc, but little is known about the events or mechanisms that initiate vascular injury and prevent its repair. In SSc, angiogenesis is incomplete or lacking despite the increased expression of a large array of pro-angiogenic factors such as VEGF. Conflicting results have recently been published concerning the presence and role of vasculogenesis and circulating endothelial progenitor cells in SSc. It remains to be established if these endothelial progenitor cells are a marker of endothelial disease or a cause of insufficient vascular repair. Human mesenchymal stem cells (MSCs) may be an alternative source for endothelial progenitor cells, and it has been observed that the angiogenic potential of endothelial-like MSCs is reduced. Other mechanisms of vascular damage include oxidative stress and factors released from activated platelets. In addition, growth factors such as ET-1 and PDGF induce proliferation of vascular smooth muscle cells resulting in intimal thickening. For the development of new therapeutic strategies, it is important to realize that the different vascular pathologies--uncompensated loss of capillaries on one hand and vascular remodelling with a proliferative vasculopathy on the other--might require different treatment approaches.

Tissue fibrosis is a major cause of morbidity and mortality in SSc. An increasing number of promising molecular targets for anti-fibrotic therapies have been described recently. However, the number of patients eligible for clinical trials is limited in SSc. The present article discusses criteria to select the most promising molecular targets for clinical trials in SSc. Based on consensus among experts, important criteria for the selection of molecular-based therapies were as follows: First, there should be strong experimental evidence that targeting the molecule of interest inhibits fibrosis. Optimally, the anti-fibrotic effects should be confirmed in at least two complementary animal models of SSc. Second, inhibitors of the molecule of interest should be clinically available. Third, clinical experience with the drug of interest in other diseases hastens the initiation of clinical trials and reduces the risk of unexpected side-effects. Finally, funding for clinical trials with the drug of interest in SSc should be available. We propose that the priority of novel targets for evaluation in clinical trials in SSc might be selected based on these consensus criteria.

In vivo cartilage contact deformation is instrumental for understanding human joint function and degeneration. This study measured the total deformation of contacting articular cartilage in the human tibiofemoral joint during in vivo weight-bearing flexion.

Antibodies that react with self-molecules occur in healthy individuals and are referred to as natural antibodies or autoantibodies. Natural autoantibodies are mainly IgM, are encoded by unmutated V(D)J genes and display a moderate affinity for self-antigens. They provide a first line of defense against infections, probably serve housekeeping functions and contribute to the homeostasis of the immune system. By contrast, high-affinity, somatically mutated IgG autoantibodies reflect a pathologic process whereby homeostatic pathways related to cell clearance, antigen-receptor signaling or cell effector functions are disturbed. In some autoimmune disorders, autoantibodies might be present before disease onset, show remarkable specificity and serve as biomarkers providing an opportunity for diagnosis and therapeutic intervention. In organ-specific autoimmune diseases, such as myasthenia gravis or pemphigus, autoantibodies directly bind to and injure target organs. In systemic autoimmune diseases, autoantibodies react with free molecules, such as phospholipids, as well as cell surface and nucleoprotein antigens, forming pathogenic antigen-antibody (immune) complexes. These autoantibodies injure tissues and organs through engagement of Fc gammaR activation of complement as well as internalization and activation of Toll-like receptors. Activation of intracellular Toll-like receptors in plasmacytoid dendritic cells leads to the production of type I interferon, whereas engagement of intracellular Toll-like receptors on antigen-presenting cells stimulates cell activation and the production of other inflammatory cytokines. Thus, immune complexes might perpetuate a positive feedback loop amplifying inflammatory responses.

To evaluate costs, benefits and cost-effectiveness of anti-TNF agents in PsA patients with inadequate response to conventional treatment.

There are no studies of fatigue levels in patients with SSc. The objective of this study was to compare fatigue in SSc to general population samples and patients with rheumatic diseases and cancer, where fatigue has been researched extensively.

To analyse consecutive patients with RA in usual rheumatology care between 1980 and 2004 at two settings for the proportion of patients taking MTX, interval from patient presentation to MTX prescription and radiographic and functional status outcomes.

To assess the therapeutic benefit of mycophenolate mofetil (MMF) in retroperitoneal fibrosis (RF).

Antigen-presenting cells (APC) play critical roles in establishing and maintaining peripheral tolerance. This is accomplished in part via expression of negative co-stimulatory molecules such as programmed death ligand-1 (PD-L1) on tolerogenic APC, such as immature myeloid dendritic cells (mDC). Several studies have strongly linked dysfunction of APC, including mDC, to the pathogenesis of SLE. The objective of this study was to determine whether APC expressed PD-L1 protein at normal levels during active lupus.