Circulating microRNA Signatures in Patients With Idiopathic and Postmenopausal Osteoporosis and Fragility Fractures

<jats:sec> <jats:title>Context:</jats:title> <jats:p>Established bone turnover markers do not reflect fracture risk in idiopathic male and premenopausal osteoporosis and the role of microRNAs (miRNAs) in these patients is currently unclear. miRNAs are a class of small non-coding RNAs that regulate gene expression and bone tissue homeostasis. They are considered a new class of endocrine regulators with promising potential as biomarkers.</jats:p> </jats:sec> <jats:sec> <jats:title>Objective:</jats:title> <jats:p>Evaluation of circulating miRNA signatures in male and female subjects with idiopathic and postmenopausal osteoporotic low-traumatic fractures.</jats:p> </jats:sec> <jats:sec> <jats:title>Design, Setting, and Patients:</jats:title> <jats:p>This was a case-control study of cross-sectional design of 36 patients with prevalent low-traumatic fractures and 39 control subjects</jats:p> </jats:sec> <jats:sec> <jats:title>Main Outcome Measures:</jats:title> <jats:p>One hundred eighty-seven miRNAs were quantified in serum by qPCR, compared between groups and correlated with established bone turnover markers.</jats:p> </jats:sec> <jats:sec> <jats:title>Results:</jats:title> <jats:p>Significant differences in serum levels of circulating miRNAs were identified in all three subgroups (46 in premenopausal, 52 in postmenopausal, 55 in male). A set of 19 miRNAs was consistently regulated in all three subgroups. Eight miRNAs [miR-152-3p, miR-30e-5p, miR-140-5p, miR-324-3p, miR-19b-3p, miR-335-5p, miR-19a-3p, miR-550a-3p] were excellent discriminators of patients with low-traumatic fractures, regardless of age and sex, with area under the curve values &gt; 0.9. The 11 remaining miRNAs showed area under the curve values between 0.81 and 0.89. Correlation analysis identified significant correlations between miR-29b-3p and P1NP, and miR-365-5p and iPTH, TRAP5b, P1NP and Osteocalcin, as well as BMDL1–L4 and miR-19b-3p, miR-324-3p, miR-532-5p, and miR-93-5p.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions:</jats:title> <jats:p>Specific serum miRNA profiles are strongly related to bone pathologies. Therefore miRNAs might be directly linked to bone tissue homeostasis. In particular, miR-29b-3p has previously been reported as regulator of osteogenic differentiation and could serve as a novel marker of bone turnover in osteoporotic patients as a member of a miRNA signature.</jats:p> </jats:sec>