Osteoporosis is the most common age-related bone disease worldwide and is usually clinically asymptomatic until the first fracture happens. MicroRNAs are critical molecular regulators in bone remodelling processes and are stabilised in the blood. The aim of this project was to identify circulatory microRNAs associated with osteoporosis using advanced PCR arrays initially and the identified differentially-expressed microRNAs were validated in clinical samples using RT-qPCR. A total of 161 participants were recruited and 139 participants were included in this study with local ethical approvals prior to recruitment. RNAs were extracted, purified, quantified and analysed from all serum and plasma samples. Differentially-expressed miRNAs were identified using miRNA PCR arrays initially and validated in 139 serum and 134 plasma clinical samples using RT-qPCR. Following validation of identified miRNAs in individual clinical samples using RT-qPCR, circulating miRNAs, hsa-miR-122-5p and hsa-miR-4516 were statistically significantly differentially-expressed between non-osteoporotic controls, osteopaenia and osteoporosis patients. Further analysis showed that the levels of these microRNAs were associated with fragility fracture and correlated with the low bone mineral density in osteoporosis patients. The results show that circulating hsa-miR-122-5p and hsa-miR-4516 could be potential diagnostic biomarkers for osteoporosis in the future.

Background Osteoporosis is the most common metabolic bone disease in the world. Since osteoporosis is clinically symptomless until the first fracture occurs, early diagnosis is critical. Calcium, along with calcium-binding and calcium-associated proteins, plays an important role in homeostasis, maintaining healthy bone metabolism. This study is aimed at investigating the level of calcium-binding/associated proteins, annexin A1, S100A4, and TMEM64, in peripheral blood mononuclear cells associated with osteoporosis and its clinical significance. Methods The levels of mRNAs of annexin A1, S100A4, and TMEM64 in human peripheral blood mononuclear cells were evaluated among 48 osteopenia and 23 osteoporosis patients compared to 17 nonosteoporotic controls. Total RNAs were isolated from clinical samples, and quantitation of mRNA levels was performed using real-time quantitative PCR. Results The levels of mRNAs for calcium-binding proteins, annexin A1 and S100A4, and calcium-associated protein, TMEM64, in human peripheral blood mononuclear cells were significantly reduced in osteopenia and osteoporosis patients compared with nonosteoporotic controls (one-way ANOVA, P < 0.0001, P = 0.039, and P = 0.0195, respectively). Annexin A1 and TMEM64 mRNAs were also significantly reduced in female osteoporosis patients over the age of 50 years compared to nonosteoporotic controls (one-way ANOVA, P = 0.004 and P = 0.0037, respectively). ROC analysis showed that the reduction in the level of mRNA for annexin A1, S100A4, or TMEM64 in the patients' peripheral blood mononuclear cells has a good diagnostic value for osteoporosis. Conclusions The results show for the first time that calcium-binding/associated proteins, annexin A1 and TMEM64, could be future diagnostic biomarkers for osteoporosis.

Dialysis patients with troponin-I levels above the cut-off value diagnostic for acute myocardial event (AME) are sometimes labeled as having "renal cause" of elevated troponin-I. Patients with troponin-I levels above 0.0 ng/mL, but below the cut-off level for an AME, are reported to have increased risk for coronary heart disease and mortality. Single pre-dialysis blood samples were taken from 150 asymptomatic dialysis patients (on hemo- or peritoneal dialysis) for troponin-I, cardiac enzymes, C-reactive protein (CRP) and lipid parameters. Troponin-I was measured by a chemiluminescent microparticle immunoassay (CMIA), of which the cut-off value for AME was set at ≥0.4 ng/mL. Patients with troponin-I levels of 0.0 ng/mL, and those with levels between 0.1 and 0.3 ng/mL, were compared regarding their cardiovascular risk profile. None of the patients had troponin-I concentrations above the cut-off level diagnostic for an AME, with 85.3% of the patients having levels of 0.0 ng/mL. While there was no difference in the "traditional" risk factors such as age, body mass index, prevalence of diabetes mellitus, hypertension, total cholesterol and low-density lipoprotein cholesterol between patients with troponin-I levels of 0.1-0.3 ng/mL and those with levels of 0.0 ng/mL, CRP concentrations were higher in the former. In peritoneal dialysis patients, the weekly Kt/V was lower in the patients with troponin levels between 0.1 and 0.3 ng/mL. The findings should add strong support in settling the debate of whether or not in patients on dialysis, falsely elevated levels of troponin-I "commonly" occur. An increased level of CRP and lower Kt/V might add to the cardiovascular risk in patients with troponin-levels between 0.1 and 0.3 ng/mL.

No abstract

No abstract