ECTS2016 Oral Communications Risk factors for fracture, Pagets disease of bone and musle and bone (6 abstracts)
High serum miRNA 550a-5p levels are risk factors for incident fractures in older postmenopausal women with type 2 diabetes
Ursula Heilmeier 1 , Matthias Hackl 4 , Susanna Skalicky 4 , Sylvia Weilner 4 , Fabian Schroeder 3 , Klemens Vierlinger 3 , Iryna Lobach 2 , Gudny Eiriksdottir 6 , Thor Aspelund 6, , Elias Gudmundsson 6 , Johannes Grillari 5 , Tamara Harris 8 , Thomas Link 1 , Vilmundur Gudnasson 6, & Ann Schwartz 2
1Department of Radiology and Biomedical Imaging, 2Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, USA; 3Department of Molecular Medicine, Austrian Institute of Technology (AIT), Vienna, Austria; 4TAmiRNA GmbH, Vienna, Austria; 5Department of Biotechnology, University of Natural Resources and Life Sciences, Vienna, Austria; 6The Icelandic Heart Association, Kopavogur, Iceland; 7Faculty of Medicine, University of Iceland, Reykjavik, Iceland; 8National Institute on Aging, Laboratory of Epidemiology and Population Sciences, Bethesda, Maryland, USA.
Standard DXA measurements, including FRAX scores, are limited in assessing fracture risk in type 2 diabetes (T2D). Novel, general applicable biomarkers are therefore needed. MicroRNAs (miRNAs) are secreted into the circulation from cells of various tissues proportional to local disease severity. Serum miRNA classifiers including miR-550a-5p were recently found to discriminate T2D women without and with prevalent fragility fractures with high specificity and sensitivity (AUC>0.90). However, the role of miR-550a-5p in predicting diabetic fragility fractures and its effect on osteogenic and adipogenic differentiation is unknown.
The AGES-Reykjavik cohort encompasses 330 T2D postmenopausal women. After excluding all subjects with bone-affecting medications/diseases, 171 T2D women remained for analysis. Of those, 71 experienced an incidence skeletal fracture during the 10-year follow-up. Baseline serum miR-550a-5p levels were determined by qPCR-arrays in all 171 T2D postmenopausal women. Decision tree models – using age and miRNA expression values as decision points – were employed to identify T2D patients at highest risk for developing incident skeletal fractures. MiR-550a-5p was further assessed by overexpression and knockdown in an in-vitro model of osteogenic differentiation and for its effect on adipogenic differentiation.
We found that T2D postmenopausal women ≥76 years had a risk of 66.7% to develop an incident skeletal fracture over the next 10 years if they had a high serum concentration of miR–550a-5p (qPCR Ct-values of <39). In contrast, T2D women ≥76 years with low serum miR-550a-5p levels (qPCR Ct-values of ≥39) had only a 30% risk of developing an incident fracture, as did subjects <76 years (23% risk). In-vitro results confirmed that miR-550a-5p inhibits osteogenic differentiation and matrix mineralization and impairs adipogenic differentiation.
Overall, these data provide first proof that biochemical markers such as serum microRNAs can be used to predict fracture risk and to identify high-risk T2D fracture groups that may benefit most from treatment.
Volume 5
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