Abstract
The assessment of fragility fracture risk based on bone densitometry and FRAX degrees, 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 degrees 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 degrees score. We found a trend towards higher OsteomiR degrees 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 degrees score was higher in osteopenic and osteoporotic subjects compared to subjects with a normal T score. Additionally, the OsteomiR degrees score predicted more fracture events than the recommended "need-to-treat" thresholds based on FRAX degrees 10-year probability. miRNAs reflect impairments in bone homeostasis several years before the occurrence of a fracture. The OsteomiR degrees score seems to be a promising miRNA panel for fragility fracture risk prediction and might have added value compared to FRAX degrees. Given the limited cohort size, further studies should be dedicated to validating the OsteomiR degrees score.