Circulating microRNA Signatures in Patients With Idiopathic and Postmenopausal Osteoporosis and Fragility Fractures.
CONTEXT 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. OBJECTIVE Evaluation of circulating miRNA signatures in male and female subjects with idiopathic and postmenopausal osteoporotic low traumatic fractures. DESIGN, SETTING, AND PATIENTS This was a case control study of cross sectional design of 36 patients with prevalent low traumatic fractures and 39 control subjects Main Outcome Measures: One hundred eighty seven miRNAs were quantified in serum by qPCR, compared between groups and correlated with established bone turnover markers. RESULTS 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 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. CONCLUSIONS 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.
The Journal of clinical endocrinology and metabolism