Context Measurement of circulating microRNAs (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 antiresorptive 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 prescreening: 50 osteoporotic patients vs 30 individuals with normal BMD. Droplet digital polymerase chain reaction (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 lower c-miR-23a-3p expression in osteoporotic patients, with or without fracture, than in osteopenic and normal subjects and increased c-miR-320a-3p expression in osteoporotic patients with fracture and 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 prescreening. 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 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.

Ciuffi, S., Marini, F., Fossi, C., Donati, S., Giusti, F., Botta, A., et al. (2022). Circulating MicroRNAs as Biomarkers of Osteoporosis and Fragility Fractures. THE JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM, 107(8), 2267-2285 [10.1210/clinem/dgac293].

Circulating MicroRNAs as Biomarkers of Osteoporosis and Fragility Fractures

Botta, Annalisa;Tarantino, Umberto;
2022

Abstract

Context Measurement of circulating microRNAs (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 antiresorptive 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 prescreening: 50 osteoporotic patients vs 30 individuals with normal BMD. Droplet digital polymerase chain reaction (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 lower c-miR-23a-3p expression in osteoporotic patients, with or without fracture, than in osteopenic and normal subjects and increased c-miR-320a-3p expression in osteoporotic patients with fracture and 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 prescreening. 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 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.
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore MED/03
English
bone phenotypes
circulating microRNAs
diagnostic biomarkers
fragility fracture
osteoporosis
Genetic Markers
Humans
Prospective Studies
Circulating MicroRNA
Osteoporosis
Osteoporotic Fractures
Ciuffi, S., Marini, F., Fossi, C., Donati, S., Giusti, F., Botta, A., et al. (2022). Circulating MicroRNAs as Biomarkers of Osteoporosis and Fragility Fractures. THE JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM, 107(8), 2267-2285 [10.1210/clinem/dgac293].
Ciuffi, S; Marini, F; Fossi, C; Donati, S; Giusti, F; Botta, A; Masi, L; Isaia, G; Marcocci, C; Migliaccio, S; Minisola, S; Nuti, R; Tarantino, U; Iantomasi, T; Brandi, Ml
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/306579
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