Distinct subsets of non-coding RNAs, including miRNAs, are associated with BMD in stressed and unstressed bone

The causes and molecular pathogenesis of postmenopausal osteoporosis (PMO) are far from understood even though osteoporotic fractures affect almost 50% of women above 50 years of age, resulting in e.g. femoral neck fractures imposing high risk to normal life. We addressed this issue by characterizing the global non-coding RNA (ncRNA) transcriptomes in non-weight bearing (unstressed) iliac and weight bearing (stressed) femoral postmenopausal bone across BMDs varying from normal (T-score >-1.0) to osteoporotic (T-score ≤ -2.5). The analyses were performed on transiliacal (84) and femoral trochanter (18) bone biopsies. Nearly 700 iliac bone ncRNAs were determined by a PCR based method and more than 6600 femoral ncRNAs were accessed by Affymetrix microchip analysis. BMD associations were calculated by linear regression and validated by Lasso analysis. DIANA TOOLS – mirPath v.3 software was used to identify overrepresented signaling pathways among the BMD associated transcripts at the two different sites.