Week-by-week changes in serum levels of bone-related circulating microRNAs and bone turnover markers.

Abstract

MicroRNAs are involved in post-transcriptional regulation of gene expression. Due to their regulatory role, microRNAs are differently expressed during specific conditions in healthy and diseased individuals, so microRNAs circulating in the blood could be used as diagnostic and prognostic biomarkers for various diseases and conditions. We want to investigate the variability of circulating microRNAs and bone turnover markers in weekly time intervals in older women. In a single-site longitudinal study, a panel of 19 bone-related miRNAs was measured using the osteomiR RT-qPCR assay in serum samples of 35 postmenopausal women divided into 3 groups: healthy controls (n= 12), low BMD (n= 14), and vertebral fractures (n= 9). Blood samples for measurement of CTX, PINP, OC, and bone ALP were collected once per week for 8weeks at 9:00AM after overnight fasting. Serum samples from all participants were analyzed for 19 microRNA bone biomarkers and 4 bone turnover markers over 8 weeks. We analyzed the data using a mixed model analysis of variance and found no significant changes between week-by-week time points in any of the groups. To estimate intraindividual variability between weekly time points, we have calculated the median coefficient of variation (CV). This was between 28.4% and 80.2% for microRNA, with an assay CV of 21.3%. It was between 8.5% and 15.6% for bone turnover markers, with an assay CV of 3.5% to 6.5%. The intraindividual variability was similar between groups. Circulating microRNAs measured in serum had a higher weekly intraindividual variability than bone turnover markers due in part to a higher assay CV.