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Circulating microRNAs as biomarkers of osteoporosis and fragility fractures.

CONTEXT
Measurement of circulating miRNAs (c-miRNAs), as potential biomarkers of fragility fracture risk, has recently become a subject of investigation.


OBJECTIVE
Measure, by next generation sequencing (NGS), global miRNA expression in serum samples of osteoporotic subjects vs individuals with normal bone mineral density (BMD).


DESIGN
Samples were collected from patients with different bone phenotypes and/or fragility fractures who did not receive any anti-resorptive and/or bone-forming drug at the time of blood collection.


SETTING
Samples and data were collected at 7 medical centers in Italy.


PATIENTS
NGS pre-screening: 50 osteoporotic patients vs 30 individuals with normal BMD. Droplet Digital PCR (ddPCR) validation: 213 patients with different bone phenotypes, including the NGS-analyzed cohort.


RESULTS
NGS identified 5 miRNAs (miR-8085, miR-320a-3p, miR-23a-3p, miR-4497, miR-145-5p) differentially expressed in osteoporosis cases without fractures vs controls. ddPCR validation confirmed a lower c-miR-23a-3p expression in osteoporotic patients, with or without fracture, than in osteopenic and normal subjects, and an increased c-miR-320a-3p expression in osteoporotic patients with fracture and a lower expression in osteoporotic patients without fracture. ddPCR analysis showed a significantly increased expression of miR-21-5p in osteoporotic patients, with or without fracture, than in osteopenic and normal subjects, not evidenced by the NGS pre-screening.


DISCUSSION
Our study confirmed levels of c-miR-23a-3p and c-miR-21-5p as able to distinguish osteoporotic patients and subjects with normal BMD. Increased levels of c-miR-320a-3p resulted specifically associated with fractures, independently by BMD, suggesting c-miR-320a-3p as a prognostic indicator of fracture risk in osteoporotic patients, to be confirmed in prospective studies on incident fractures.