The development of Taiwan Fracture Liaison Service network

Osteoporosis and its associated fragility fractures are becoming a severe burden in the healthcare system globally. In the Asian-Pacific (AP) region, the rapidly increasing in aging population is the main reason accounting for the burden. Moreover, the paucity of quality care for osteoporosis continues to be an ongoing challenge. The Fracture Liaison Service (FLS) is a program promoted by International Osteoporosis Foundation (IOF) with a goal to improve quality of postfracture care and prevention of secondary fractures. In this review article, we would like to introduce the Taiwan FLS network. The first 2 programs were initiated in 2014 at the National Taiwan University Hospital and its affiliated Bei-Hu branch. Since then, the Taiwan FLS program has continued to grow exponentially. Through FLS workshops promoted by the Taiwanese Osteoporosis Association (TOA), program mentors have been able to share their valuable knowledge and clinical experience in order to promote establishments of additional programs. With 22 FLS sites including 11 successfully accredited on the best practice map, Taiwan remains as one of the highest FLS coverage countries in the AP region, and was also granted the IOF Best Secondary Fracture Prevention Promotion award in 2017. Despite challenges faced by the TOA, we strive to promote more FLS sites in Taiwan with a main goal of ameliorating further health burden in managing osteoporotic patients.

An updated hip fracture projection in Asia: The Asian Federation of Osteoporosis Societies study

OBJECTIVES: Hip fracture is a major public health problem. Earlier studies projected that the total number of hip fracture will increase dramatically by 2050, and most of the hip fracture will occur in Asia. To date, only a few studies provided the updated projection, and none of them focused on the hip fracture projection in Asia. Thus, it is essential to provide the most up to date prediction of hip fracture in Asia, and to evaluate the total direct medical cost of hip fracture in Asia. METHODS: We provide the updated projection of hip fracture in 9 Asian Federation of Osteoporosis Societies members using the most updated incidence rate and projected population size. RESULTS: We show that the number of hip fracture will increase from 1,124,060 in 2018 to 2,563,488 in 2050, a 2.28-fold increase. This increase is mainly due to the changes on the population demographics, especially in China and India, which have the largest population size. The direct cost of hip fracture will increase from 9.5 billion United State dollar (USD) in 2018 to 15 billion USD in 2050, resulting a 1.59-fold increase. A 2%–3% decrease in incidence rate of hip fracture annually is required to keep the total number of hip fracture constant over time. CONCLUSIONS: The results show that hip fracture remains a key public health issue in Asia, despite the available of better diagnosis, treatment, and prevention of fracture over the recent years. Healthcare policy in Asia should be aimed to reduce the burden of hip fracture.

Interleukin-20 targets podocytes and is upregulated in experimental murine diabetic nephropathy

Interleukin (IL)-20, a proinflammatory cytokine of the IL-10 family, is involved in acute and chronic renal failure. The aim of this study was to elucidate the role of IL-20 during diabetic nephropathy development. We found that IL-20 and its receptor IL-20R1 were upregulated in the kidneys of mice and rats with STZ-induced diabetes. In vitro, IL-20 induced MMP-9, MCP-1, TGF-β1 and VEGF expression in podocytes. IL-20 was upregulated by hydrogen peroxide, high-dose glucose and TGF-β1. In addition, IL-20 induced apoptosis in podocytes by activating caspase-8. In STZ-induced early diabetic nephropathy, IL-20R1-deficient mice had lower blood glucose and serum BUN levels and a smaller glomerular area than did wild-type controls. Anti-IL-20 monoclonal antibody (7E) treatment reduced blood glucose and the glomerular area and improved renal functions in mice in the early stage of STZ-induced diabetic nephropathy. ELISA showed that the serum IL-20 level was higher in patients with diabetes mellitus than in healthy controls. The findings of this study suggest that IL-20 induces cell apoptosis of podocytes and plays a role in the pathogenesis of early diabetic nephropathy.

Relationship between the FRAX® score and falls in community-dwelling middle-aged and elderly people

OBJECTIVES: Falls is a risk factor for fracture. The FRAX® predicts fractures. Whether the FRAX® is associated with fall in both gender is inconclusive. The aim of our study is to evaluate the association between FRAX scores and falls. METHODS: The cross-sectional study set from 2009 to 2010 included 1200 community-dwelling people who were systematically sampled in central Taiwan. The 1200 participants (men: 524; women: 676; ≥40 years old) completed questionnaires about socioeconomic status; lifestyle; medical and fall history were completed. FRAX scores with and without bone mineral density (BMD) were calculated by using the Taiwan calculator. RESULTS: A total of 19.8% participants fell down. Binary regression models showed that diabetes mellitus history (OR: 1.61; 95% CI: 1.03–2.52), the FRAX without BMD in a continuous major score (OR: 1.06; 95% CI: 1.03–1.09), continuous hip score (OR: 1.11; 95% CI: 1.05–1.16), categorical major score ≥ 10% (OR: 1.81; 95% CI: 1.25–2.61), and categorical hip score ≥ 3% (OR: 1.80; 95% CI: 1.30–2.50) were independent risk factors for falls. FRAX with BMD in a continuous major score (OR: 1.04; 95% CI: 1.02–1.06), continuous hip score (OR: 1.06; 95% CI: 1.02–1.09), categorical major score ≥ 10% (OR: 1.52; 95% CI: 1.09–2.12), and categorical hip score ≥ 3% (OR: 1.53; 95% CI: 1.13–2.09) were also independent risk factors. CONCLUSIONS: We concluded that FRAX® scores with and without BMD were unanimously correlated with falls in community-dwelling middle-aged and elderly males and females.

Dipyrone & 2,5-dimethylcelecoxib suppress Th2-related chemokine production in monocyte.

Background & objectives: Selective cyclooxygenase-2 (COX-2) inhibitor is a form of non steroidal anti-inflammatory drug (NSAID) and is commonly used in autoimmune and rheumatic diseases to control inflammation and alleviate pain. Tumour necrosis factor-alpha (TNF-α) production and an imbalance of T helper 1 (Th1)/Th2 contribute to the pathogenesis of autoimmune and also anti-tumour activity. Dipyrone is a NSAID used to treat pain worldwide. The celecoxib analogue, 2,5-dimethylcelecoxib (DMC), lacks COX-2 inhibitory activity but exhibits anti-tumour properties. However, the effects and the mechanisms of dipyrone and 2,5-dimethylcelecoxib on tumour necrosis factor (TNF)-α and Th1- and Th2-related chemokines in monocytes remain poorly defined. This study was carried out to investigate the effects of dipyrone and 2,5-dimethylcelecoxib on the expression of Th1 (IP-10) and Th2 (I-309 and MDC) and TNF-α in human monocytes and the associated intracellular mechanism. methods: THP-1 cells and peripheral blood mononuclear cells (PBMCs) were pre-treated with dipyrone (10-9 – 10-4 M) and 2,5-dimethylcelecoxib (10-9 – 10-5 M) 2 h before lipopolysaccharide (LPS) stimulation. Cell supernatant was collected 24 h after LPS stimulation. TNF-α, I-309, MDC and IP-10 concentrations of cell supernatants were determined using ELISA. Intracellular signaling was evaluated by western blot. results: Dipyrone and 2,5-dimethylcelecoxib downregulated LPS-induced Th2-related chemokine I-309 and macrophage derived chemokine (MDC) production. Only high dose of 2,5-dimethylcelecoxib (10-5 M), but not dipyrone downregulated LPS-induced IP-10. Only very high dose of 2,5-dimethylcelecoxib had effect on LPS-induced TNF-α expression in PBMCs. Dipyrone and 2,5-dimethylcelecoxib suppressed LPS-induced p65 and JNK MAPK (C-Jun N-terminal kinase mitogen activated protein kinase). expression. Interpretation & conclusions: Dipyrone and 2,5-dimethylcelecoxib downregulated LPS-induced Th2-related chemokine I-309 and MDC in THP-1 cells. The suppressive effect on Th2-related

Epigenetic regulation in allergic diseases and related studies

Asthma, a chronic inflammatory disorder of the airway, has features of both heritability as well as environmental influences which can be introduced in utero exposures and modified through aging, and the features may attribute to epigenetic regulation. Epigenetic regulation explains the association between early prenatal maternal smoking and later asthma-related outcomes. Epigenetic marks (DNA methylation, modifications of histone tails or noncoding RNAs) work with other components of the cellular regulatory machinery to control the levels of expressed genes, and several allergy- and asthma-related genes have been found to be susceptible to epigenetic regulation, including genes important to T-effector pathways (IFN-γ, interleukin [IL] 4, IL-13, IL-17) and T-regulatory pathways (FoxP3). Therefore, the mechanism by which epigenetic regulation contributes to allergic diseases is a critical issue. In the past most published experimental work, with few exceptions, has only comprised small observational studies and models in cell systems and animals. However, very recently exciting and elegant experimental studies and novel translational research works were published with new and advanced technologies investigating epigenetic mark on a genomic scale and comprehensive approaches to data analysis. Interestingly, a potential link between exposure to environmental pollutants and the occurrence of allergic diseases is revealed recently, particular in developed and industrialized countries, and endocrine disrupting chemicals (EDCs) as environmental hormone may play a key role. This review addresses the important question of how EDCs (nonylphenol, 4 octylphenol, and phthalates) influences on asthma-related gene expression via epigenetic regulation in immune cells, and how anti-asthmatic agents prohibit expression of inflammatory genes via epigenetic modification. The discovery and validation of epigenetic biomarkers linking exposure to allergic diseases might lead to better epigenotyping of risk, prognosis, treatment prediction, and development of novel therapies.

The Effects of Environmental Toxins on Allergic Inflammation

The prevalence of asthma and allergic disease has increased worldwide over the last few decades. Many common environmental factors are associated with this increase. Several theories have been proposed to account for this trend, especially those concerning the impact of environmental toxicants. The development of the immune system, particularly in the prenatal period, has far-reaching consequences for health during early childhood, and throughout adult life. One underlying mechanism for the increased levels of allergic responses, secondary to exposure, appears to be an imbalance in the T-helper function caused by exposure to the toxicants. Exposure to environmental endocrine-disrupting chemicals can result in dramatic changes in cytokine production, the activity of the immune system, the overall Th1 and Th2 balance, and in mediators of type 1 hypersensitivity mediators, such as IgE. Passive exposure to tobacco smoke is a common risk factor for wheezing and asthma in children. People living in urban areas and close to roads with a high volume of traffic, and high levels of diesel exhaust fumes, have the highest exposure to environmental compounds, and these people are strongly linked with type 1 hypersensitivity disorders and enhanced Th2 responses. These data are consistent with epidemiological research that has consistently detected increased incidences of allergies and asthma in people living in these locations. During recent decades more than 100,000 new chemicals have been used in common consumer products and are released into the everyday environment. Therefore, in this review, we discuss the environmental effects on allergies of indoor and outside exposure.

Bioavailability evaluation of naphthalene in soil using persulfate oxidation and ultrasonic extraction method.

Bioavailability is defined as the fraction of a soil contaminant readily available for microbial degradation and for naphthalene it could be estimated by conventional exhaustive extraction methods. In this study, a novel method that employed persulfate oxidation in combination with ultrasonic extraction (POUSE) was developed. Three parameters, temperature, duration of persulfate oxidation, and the ratio of persulfate to soil organic matter (S2O8 2- /SOM; g g-1), were investigated to obtain an optimum operating conditions. Under the condition, naphthalene bioavailability estimated by the POUSE method was verified and compared with other three exhaustive methods i.e. sonicator, supercritical fluid extraction (SFE), and soxhlet extraction (SE). When the S2O8 2-/SOM ratio was controlled at 11.6 g g-1, the optimum operating conditions of the POUSE method were 70oC and 3 hr, for the temperature and duration. Under these conditions, the residual naphthalene concentrations were correlated well with the residual naphthalene concentrations for both the cases of freshly spiked and aged soils. By contrast, the sonicator, SFE, and the SE overestimated the naphthalene bioavailability since these three methods extracted naphthalene much more than that of biodegradation test. These results demonstrated that the POUSE could estimate more precisely the naphthalene bioavailability.