MicroRNA biomarkers for osteoporosis – lessons learned: opportunities and challenges for diagnosis and monitoring of bone diseases

Introduction MicroRNAs regulate gene expression. More than 60 % of human coding genes are controlled by microRNAs, including many important regulators of bone formation and resorption. Research regarding the interplay between microRNAs and mRNAs in vitro and in vivo has resulted in the identification of potentially novel drug targets such as miR-34a-5 p or miR-214-3 p.

Methods At the same time, it was shown that active or passive release of microRNAs from (bone) cells enables minimal-invasive detection of microRNAs in so-called liquid biopsies such as serum, plasma or urine. Since 2013, we have investigated the changes in the circulating miRNome in various musculo-skeletal disease populations such as postmenopausal women with all types of major osteoporotic fractures, type-2 diabetic women with fractures, WNT1 mutation positive individuals, and male osteoporosis. In addition, we have performed a longitudinal analysis of circulating microRNAs in a rodent model of postmenopausal osteoporosis, where we evaluated the effects of anti-resorptive and anabolic treatment on microRNA expression. This lead to the discovery of a panel of microRNAs with potential clinical utility for prognosis, diagnosis and monitoring of disease – called osteomiR. We have investigated the effects of pre-analytical processing, inter- and intra-individual variability, circadian rhythm, and fracture healing on these bone biomarkers to identify potential sources of variability as well as association to bone turnover markers.

Results This abstract will provide a summary of the results obtained so far and will highlight results for selected osteomiRs such as miR-203a-3 p, miR-31-5 p, miR-214-3 p, or miR-550a. Finally, results from a health-economic perspective on implementing microRNA biomarkers for the prognosis of fracture-risk will be presented.

Korrespondenzadresse Matthias Hackl, TAmiRNA GmbH, Leberstrasse 20, 1110 Wien, Österreich,

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