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- Title
Circulating MicroRNAs as Biomarkers of Osteoporosis and Fragility Fractures.
- Authors
Ciuffi, Simone; Marini, Francesca; Fossi, Caterina; Donati, Simone; Giusti, Francesca; Botta, Annalisa; Masi, Laura; Isaia, Giancarlo; Marcocci, Claudio; Migliaccio, Silvia; Minisola, Salvatore; Nuti, Ranuccio; Tarantino, Umberto; Iantomasi, Teresa; Brandi, Maria Luisa
- 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.
- Subjects
MICRORNA; OSTEOPOROSIS diagnosis
- Publication
Journal of Clinical Endocrinology & Metabolism, 2022, Vol 107, Issue 8, p2267
- ISSN
0021-972X
- Publication type
Article
- DOI
10.1210/clinem/dgac293