Association of JAG1 with bone mineral density and osteoporotic fractures: a genome-wide association study and follow-up replication studies.

Bone mineral density (BMD), a diagnostic parameter for osteoporosis and a clinical predictor of fracture, is a polygenic trait with high heritability. To identify genetic variants that influence BMD in different ethnic groups, we performed a genome-wide association study (GWAS) on 800 unrelated Southern Chinese women with extreme BMD and carried out follow-up replication studies in six independent study populations of European descent and Asian populations including 18,098 subjects. In the meta-analysis, rs2273061 of the Jagged1 (JAG1) gene was associated with high BMD (p = 5.27 x 10(-8) for lumbar spine [LS] and p = 4.15 x 10(-5) for femoral neck [FN], n = 18,898). This SNP was further found to be associated with the low risk of osteoporotic fracture (p = 0.009, OR = 0.7, 95% CI 0.57-0.93, n = 1881). Region-wide and haplotype analysis showed that the strongest association evidence was from the linkage disequilibrium block 5, which included rs2273061 of the JAG1 gene (p = 8.52 x 10(-9) for LS and 3.47 x 10(-5) at FN). To assess the function of identified variants, an electrophoretic mobility shift assay demonstrated the binding of c-Myc to the "G" but not "A" allele of rs2273061. A mRNA expression study in both human bone-derived cells and peripheral blood mononuclear cells confirmed association of the high BMD-related allele G of rs2273061 with higher JAG1 expression. Our results identify the JAG1 gene as a candidate for BMD regulation in different ethnic groups, and it is a potential key factor for fracture pathogenesis.

Protein, amino acid, and peptide supplementation for the treatment of sarcopaenia.

Sarcopaenia is an age-related disease affected by many factors, nutrition being one. Reduced protein intake and decreased diet quality are correlated with sarcopaenia. Protein, amino acid, or peptide supplementation is a commonly used clinical practice to increase protein intake. However, whether supplementation plays a key role in preventing and treating sarcopaenia and whether it needs to be combined with other interventions is worthy of study. This review focuses on protein, amino acid, and peptide supplementation for the prevention and treatment of sarcopaenia.

Liraglutide Inhibits Osteoclastogenesis and Improves Bone Loss by Downregulating Trem2 in Female Type 1 Diabetic Mice: Findings From Transcriptomics.

Background: The mechanisms of bone fragility in type 1 diabetes (T1D) are not fully understood. Whether glucagon-like peptide-1 receptor (GLP-1R) agonists could improve bone quality in T1D context also remains elusive. Aims: We aimed to explore the possible mechanisms of bone loss in T1D and clarify whether liraglutide has effects on bone quality of T1D mice using transcriptomics. Methods: Female streptozotocin-induced diabetic C57BL/6J mice were randomly divided into four groups and received the following treatments daily for 8 weeks: saline as controls, insulin, liraglutide, and liraglutide combined with insulin. These groups were also compared with non-STZ-treated normal glucose tolerance (NGT) group. Trunk blood and bone tissues were collected for analysis. Three tibia from each of the NGT, saline-treated, and liraglutide-treated groups were randomly selected for transcriptomics. Results: Compared with NGT mice, saline-treated T1D mice manifested markedly hyperglycemia and weight loss, and micro-CT revealed significantly lower bone mineral density (BMD) and deficient microarchitectures in tibias. Eight weeks of treatment with liraglutide alone or combined with insulin rescued the decreased BMD and partly corrected the compromised trabecular microarchitectures. Transcriptomics analysis showed there were 789 differentially expressed genes mainly mapped to osteoclastogenesis and inflammation pathways. The RT-qPCR verified that the gene expression of Trem2, Nfatc1, Trap, and Ctsk were significantly increased in the tibia of T1D compared with those in the NGT group. Liraglutide treatment alone or combined with insulin could effectively suppress osteoclastogenesis by downregulating the gene expression of Trem2, Nfatc1, Ctsk, and Trap. Conclusions: Taken together, increased osteoclastogenesis with upregulated expression of Trem2 played an important role in bone loss of T1D mice. Liraglutide provided protective effects on bone loss in T1D mice by suppressing osteoclastogenesis.

The effects of oral nutritional supplements in patients with maintenance dialysis therapy: A systematic review and meta-analysis of randomized clinical trials.

BACKGROUND/OBJECTIVE: This systematic review aims to determine the potential effects of oral nutritional supplements (ONS) in patients receiving maintenance dialysis therapy (MDT). METHODS: Electronic databases were searched without language limits through to July 2018. Randomized controlled trials (RCTs) that involved comparisons of ONS versus placebo or routine care are included in this meta-analysis. RevMan 5.3 statistical software was used for meta-analysis. RESULTS: 15 articles with 589 subjects were included in our study. There are insufficient comparable data of randomized trials to allow meta-analysis of mortality. Albumin levels may be improved by the macronutrient blends or protein/amino acid supplements in MDT patients. Compared with the control group, serum albumin levels and BMI in the ONS group were increased by 1.58 g/L (95% CI, 0.52-2.63, P = 0.003; I2 = 85%) and 0.40 kg/m2 (95% CI, 0.10-0.71, P = 0.01; I2 = 49%), respectively. In the subgroup analysis of patients receiving hemodialysis, albumin levels in ONS group were increased by 2.17 g/L (95% CI, 0.89-3.45, P<0.001; I2 = 90%). ONS may not influence serum phosphorus and potassium levels. CONCLUSIONS: Very low-quality evidence suggests that Short-term oral energy or protein/amino acid supplements may improve nutritional status by increasing serum albumin levels and BMI in MDT patients, without influence on serum potassium levels. High-quality and large RCTs, particularly regarding the effects of ONS on mortality and quality of life, are needed to further validate our findings.

Rapidly increasing rates of hip fracture in Beijing, China.

The age-specific rates of hip fractures have been declining in most countries in the West but a few studies suggest that the rates might be increasing in areas of Asia that are undergoing urbanization. We previously conducted a population-based study of hip fracture rates in Beijing, China, in 1990 to 1992 that included validation of hip fracture cases. Using a similar approach to validate cases, we estimated the age-specific hip fracture rates in Beijing, China, for 2002 to 2006. Specifically, we obtained hospital discharge data for hip fractures that were reported to the Beijing Bureau of Public Health. To confirm the diagnoses, Beijing residence, and find cases missed by the public records we checked individual cases in the public health records against medical records in a random sample of Beijing hospitals. The rates from public health data were adjusted for these under- and overestimations. We found that between 1990 and 1992 and 2002 and 2006, the adjusted age-specific rates of hip fracture over age 50 years increased 2.76-fold (95% confidence interval [CI], 2.68-2.84) in women and 1.61-fold (95% CI, 1.56-1.66) in men. Over age 70 years, the age-specific rates increased 3.37-fold (95% CI, 3.28-3.47) in women and 2.01-fold (95% CI, 1.95-2.07) in men. From 2002 to 2006, the rates over age 50 years increased 58% in women and 49% in men. We conclude that the rate of hip fracture has been rising very rapidly in Beijing, China. Therefore, the burden of hip fractures may be shifting rapidly from the West to urbanizing areas of the East.