title: Circulating microRNA Signatures in Patients With Idiopathic and Postmenopausal Osteoporosis and Fragility Fractures.
abstract: 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.
  
  
  
  Evaluation of circulating miRNA signatures in male and female subjects with idiopathic and postmenopausal osteoporotic low-traumatic fractures.
  
  
  
  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.
  
  
  
  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-L4and miR-19b-3p, miR-324-3p, miR-532-5p, and miR-93-5p.
  
  
  
  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.
authors.affiliation: 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.
authors.forename: Roland
authors.initials: R
authors.lastname: Kocijan
authors.affiliation: 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.
authors.forename: Christian
authors.initials: C
authors.lastname: Muschitz
authors.affiliation: 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.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Geiger
authors.affiliation: 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.
authors.forename: Susanna
authors.initials: S
authors.lastname: Skalicky
authors.affiliation: 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.
authors.forename: Andreas
authors.initials: A
authors.lastname: Baierl
authors.affiliation: 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.
authors.forename: Rainer
authors.initials: R
authors.lastname: Dormann
authors.affiliation: 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.
authors.forename: Fabian
authors.initials: F
authors.lastname: Plachel
authors.affiliation: 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.
authors.forename: Xaver
authors.initials: X
authors.lastname: Feichtinger
authors.affiliation: 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.
authors.forename: Patrick
authors.initials: P
authors.lastname: Heimel
authors.affiliation: 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.
authors.forename: Astrid
authors.initials: A
authors.lastname: Fahrleitner-Pammer
authors.affiliation: 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.
authors.forename: Johannes
authors.initials: J
authors.lastname: Grillari
authors.affiliation: 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.
authors.forename: Heinz
authors.initials: H
authors.lastname: Redl
authors.affiliation: 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.
authors.forename: Heinrich
authors.initials: H
authors.lastname: Resch
authors.affiliation: 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.
authors.forename: Matthias
authors.initials: M
authors.lastname: Hackl
mesh_terms: D015502:Absorptiometry, Photon; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D010024:Osteoporosis / Q000097:blood* / Q000000981:diagnostic imaging; D015663:Osteoporosis, Postmenopausal / Q000097:blood / Q000000981:diagnostic imaging; D058866:Osteoporotic Fractures / Q000097:blood* / Q000000981:diagnostic imaging; D017698:Postmenopause / Q000097:blood*; D017697:Premenopause / Q000097:blood*
chemical_list: D015415:Biomarkers; D035683:MicroRNAs