Serum levels of osteoprotegerin and receptor activator of nuclear factor -κB ligand in children with early juvenile idiopathic arthritis: a 2-year prospective controlled study

<p>Abstract</p> <p>Background</p> <p>The clinical relevance of observations of serum levels of osteoprotegerin (OPG) and receptor activator of nuclear factor -κB ligand (RANKL) in juvenile idiopathic arthritis (JIA) is not clear. To elucidate the potential role of OPG and RANKL in JIA we determined serum levels of OPG and RANKL in patients with early JIA compared to healthy children, and prospectively explored changes in relation to radiographic score, bone and lean mass, severity of the disease, and treatment.</p> <p>Methods</p> <p>Ninety children with early oligoarticular or polyarticular JIA (ages 6-18 years; mean disease duration 19.4 months) and 90 healthy children individually matched for age, sex, race, and county of residence, were examined at baseline and 2-year follow-up. OPG and RANKL were quantified by enzyme-immunoassay. Data were analyzed with the use of t-tests, ANOVA, and multiple regression analyses.</p> <p>Results</p> <p>Serum OPG was significantly lower in patients than controls at baseline, and there was a trend towards higher RANKL and a lower OPG/RANKL ratio. Patients with polyarthritis had significantly higher increments in RANKL from baseline to follow-up, compared to patients with oligoarthritis. RANKL was a significant negative predictor for increments in total body lean mass. Patients who were receiving corticosteroids (CS) or disease-modifying antirheumatic drugs (DMARDs) at follow-up had higher OPG/RANKL ratio compared with patients who did not receive this medication.</p> <p>Conclusions</p> <p>The data supports that levels of OPG are lower in patients with JIA compared to healthy children, and higher levels of RANKL is associated with more serious disease. RANKL was a significant negative predictor of lean mass in patients with JIA. The OPG/RANKL ratio was higher in patients on DMARDs or CS treatment.</p

The impact of inflammation on bone mass in children

Bone is a dynamic tissue. Skeletal bone integrity is maintained through bone modeling and remodeling. The mechanisms underlying this bone mass regulation are complex and interrelated. An imbalance in the regulation of bone remodeling through bone resorption and bone formation results in bone loss. Chronic inflammation influences bone mass regulation. Inflammation-related bone disorders share many common mechanisms of bone loss. These mechanisms are ultimately mediated through the uncoupling of bone remodeling. Cachexia, physical inactivity, pro-inflammatory cytokines, as well as iatrogenic factors related to effects of immunosuppression are some of the common mechanisms. Recently, cytokine signaling through the central nervous system has been investigated for its potential role in bone mass dysregulation in inflammatory conditions. Growing research on the molecular mechanisms involved in inflammation-induced bone loss may lead to more selective therapeutic targeting of these pathological signaling pathways

Are low-value care measures up to the task? A systematic review of the literature

Background Reducing low-value care is a core component of healthcare reforms in many Western countries. A comprehensive and sound set of low-value care measures is needed in order to monitor low-value care use in general and in provider-payer contracts. Our objective was to review the scientific literature on low-value care measurement, aiming to assess the scope and quality of current measures. Methods A systematic review was performed for the period 2010–2015. We assessed the scope of low-value care recommendations and measures by categorizing them according to the Classification of Health Care Functions. Additionally, we assessed the quality of the measures by 1) analysing their development process and the level of evidence underlying the measures, and 2) analysing the evidence regarding the validity of a selected subset of the measures. Results Our search yielded 292 potentially relevant articles. After screening, we selected 23 articles eligible for review. We obtained 115 low-value care measures, of which 87 were concentrated in the cure sector, 25 in prevention and 3 in long-term care. No measures were found in rehabilitative care and health promotion. We found 62 measures from articles that translated low-value care recommendations into measures, while 53 measures were previously developed by institutions as the National Quality Forum. Three measures were assigned the highest level of evidence, as they were underpinned by both guidelines and literature evidence. Our search yielded no information on coding/criterion validity and construct validity for the included measures. Despite this, most measures were already used in practice. Conclusion This systematic review provides insight into the current state of low-value care measures. It shows that more attention is needed for the evidential underpinning and quality of these measures. Clear information about the level of evidence and validity helps to identify measures that truly represent low-value care and are sufficiently qualified to fulfil their aims through quality monitoring and in innovative payer-provider contracts. This will contribute to creating and maintaining the support of providers, payers, policy makers and citizens, who are all aiming to improve value in health care