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评估一组 miRNA 预测脆性骨折风险:一项初步研究。

Evaluation of a Panel of MicroRNAs that Predicts Fragility Fracture Risk: A Pilot Study.

机构信息

Clinical Chemistry Department / CHU de Liège, Avenue de L'Hopital, 1, 4000, Liège, Belgium.

Public Health, Epidemiology and Health Economics Department, ULiège, Liège, Belgium.

出版信息

Calcif Tissue Int. 2020 Mar;106(3):239-247. doi: 10.1007/s00223-019-00628-8. Epub 2019 Nov 15.

DOI:10.1007/s00223-019-00628-8
PMID:31729554
Abstract

The assessment of fragility fracture risk based on bone densitometry and FRAX°, although commonly used, has shown some limitations. MicroRNAs (miRNAs) are promising biomarkers known to regulate post-transcriptional gene expression. Many studies have already shown that microRNAs are involved in bone homeostasis by modulating osteoblast and osteoclast gene expression. In this pilot study, we investigated the ability of an miRNA panel (namely, the OsteomiR° score) to predict fragility fracture risk in older people. miRNAs were extracted from the sera of 17 persons who developed a fracture within 3 years of collecting the serum and 16 persons who did not experience fractures in the same period. Nineteen miRNAs known to be involved in bone homeostasis were assessed, and 10 miRNAs were employed to calculate the OsteomiR° score. We found a trend towards higher OsteomiR° scores in individuals who experienced fractures compared to control subjects. The most suitable cut-off that maximized sensitivity and specificity was determined by ROC curve analysis, and a positive predictive value of 68% and a sensitivity of 76% were obtained. The OsteomiR° score was higher in osteopenic and osteoporotic subjects compared to subjects with a normal T score. Additionally, the OsteomiR° score predicted more fracture events than the recommended "need-to-treat" thresholds based on FRAX° 10-year probability. miRNAs reflect impairments in bone homeostasis several years before the occurrence of a fracture. The OsteomiR° score seems to be a promising miRNA panel for fragility fracture risk prediction and might have added value compared to FRAX°. Given the limited cohort size, further studies should be dedicated to validating the OsteomiR° score.

摘要

基于骨密度测定和 FRAX°评估的脆性骨折风险,虽然应用广泛,但也存在一些局限性。microRNAs(miRNAs)是一种有前途的生物标志物,已知可调节转录后基因表达。许多研究已经表明,miRNAs 通过调节成骨细胞和破骨细胞基因表达,参与骨稳态的调节。在这项初步研究中,我们研究了 miRNA 谱(即 OsteomiR°评分)预测老年人脆性骨折风险的能力。从在收集血清后 3 年内发生骨折的 17 人和同期未发生骨折的 16 人血清中提取 miRNA。评估了 19 种已知与骨稳态有关的 miRNA,并采用 10 种 miRNA 计算 OsteomiR°评分。我们发现,与对照组相比,发生骨折的个体的 OsteomiR°评分呈上升趋势。通过 ROC 曲线分析确定了最大灵敏度和特异性的最佳截断值,获得了 68%的阳性预测值和 76%的灵敏度。与 T 评分正常的患者相比,骨质疏松和骨质疏松症患者的 OsteomiR°评分更高。此外,与基于 FRAX°10 年概率的推荐“需要治疗”阈值相比,OsteomiR°评分预测了更多的骨折事件。miRNAs 在骨折发生前几年就反映了骨稳态的损伤。OsteomiR°评分似乎是一种有前途的脆性骨折风险预测 miRNA 谱,与 FRAX°相比可能具有额外的价值。鉴于样本量有限,应进一步开展研究以验证 OsteomiR°评分。

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