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

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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.

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Acknowledgements

We express our sincere thanks to Matthias Hackl, Susanna Skalicky and the TamiRNA GbmH team for providing technical support for the experiments.

Funding

This study was supported by clinical chemistry department and Fondation Léon Fredericq.

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Authors and Affiliations

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

    Aurélie Ladang & Etienne Cavalier

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

    Charlotte Beaudart, Médéa Locquet, Jean-Yves Reginster & Olivier Bruyère

  3. Chair for Biomarkers of Chronic Diseases, Biochemistry Department, College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia

    Jean-Yves Reginster

  4. Centre Académique de Recherche Et D’Expérimentation en Santé (CARES SPRL), Liège, Belgium

    Jean-Yves Reginster

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  1. Aurélie Ladang
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  2. Charlotte Beaudart
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  3. Médéa Locquet
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  4. Jean-Yves Reginster
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  5. Olivier Bruyère
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  6. Etienne Cavalier
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Correspondence to Aurélie Ladang.

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Conflict of interest

JYR is a member of paid advisory boards for IBSA-GENEVRIER, MYLAN, RADIUS HEALTH, PIERRE FABRE; upon invitation, is a paid lecturer of sponsor for IBSA-GENEVRIER, MYLAN, CNIEL, DAIRY RESEARCH COUNCIL (DRC) and received grant support from industry (all through the Institution) from IBSA-GENEVRIER, MYLAN, CNIEL, RADIUS HEALTH. All other authors state that they have no conflicts of interest.

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Ladang, A., Beaudart, C., Locquet, M. et al. Evaluation of a Panel of MicroRNAs that Predicts Fragility Fracture Risk: A Pilot Study. Calcif Tissue Int 106, 239–247 (2020). https://doi.org/10.1007/s00223-019-00628-8

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  • DOI: https://doi.org/10.1007/s00223-019-00628-8

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