Analysis of the Bone MicroRNome in Osteoporotic Fractures

Osteoporosis causes important morbidity among elderly individuals. Fragility fractures, and especially hip fractures, have a particularly negative impact on the patients' quality of life. The role of epigenetic mechanisms in the pathogenesis of many disorders is increasingly recognized, yet little is known about their role in non-malignant bone disorders such as osteoporosis. The aim of this study was to explore the expression of miRNAs in patients with osteoporotic hip fractures. Trabecular bone samples were obtained from the femoral heads of patients undergoing replacement surgery for osteoporotic hip fractures and non-fracture controls with hip osteoarthritis. Levels of 760 miRNA were analyzed by real-time PCR. Thirteen miRNAs showed nominally significant (p < 0.05) differences between both groups. Six miRNAs (miR-187, miR-193a-3p, miR-214, miR518f, miR-636, and miR-210) were selected for the replication stage. These miRNAs were individually analyzed in a larger group of 38 bone samples. At this stage, we confirmed statistically significant differences across groups for mir-187 and miR-518f. The median relative expression levels of miR-187 were 5.3-fold higher in the non-fracture group (p = 0.002). On the contrary, miR-518f was preferentially expressed in bones from osteoporotic patients (8.6-fold higher in fractures; p = 0.046). In this first hypothesis-free study of the bone microRNome we found two miRNAs, miR-187, and miR-518f, differentially regulated in osteoporotic bone. Further studies are needed to elucidate the mechanisms involved in the association of these miRNAs with fractures.