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J Clin Endocrinol Metab. 2016 Nov;101(11):4125-4134. Epub 2016 Aug 23.

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

Author information

1
St. Vincent Hospital-Medical Department II (R.K., C.M., R.D., F.P., X.F., H.Res.), The VINFORCE Study Group, Academic Teaching Hospital of Medical University of Vienna, 1090 Vienna, Austria; TAmiRNA, GmbH (E.G., S.S, M.H..), 1190 Vienna, Austria; Department of Statistics and Operations Research (A.B.), University of Vienna, 1090 Vienna, Austria; Ludwig Boltzmann Institute for Experimental and Clinical Traumatology (R.K., P.H., H.Red.), 1200 Vienna, Austria; Karl Donath Laboratory for Hard Tissue and Biomaterial Research, Department of Oral Surgery (P.H.), Medical University of Vienna, 1090 Vienna, Austria; Department of Internal Medicine, Division of Endocrinology and Diabetes (A.F.-P.), Medical University of Graz, 8010 Graz, Austria; Christian Doppler Laboratory on Biotechnology of Skin Aging, Department of Biotechnology (J.G.), University of Natural Resources and Life Sciences Vienna, 1180 Viena, Austria; Austrian Cluster for Tissue Regeneration (H.Red., J.G.), Department of Traumatology, Medical University of Vienna, 1090 Vienna, Austria; and Medical Faculty of Bone Diseases (H.Red.), Sigmund Freud University-Vienna, 1020 Vienna, Austria.

Abstract

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.

PMID:
27552543
DOI:
10.1210/jc.2016-2365
[Indexed for MEDLINE]

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