Osteoporosis is a debilitating and costly bone condition that causes fractures in 33% of women and 20% of men over the age of 50. Recent studies have shown that beta blocker (BB) users have higher bone mineral density (BMD) and decreased risk of fracture as compared to non-users. Adrenergic signaling in osteoblasts leads to decreased BMD in rodent models, but the occurrence and mechanism are unknown in humans. Furthermore, miRNAs are associated with adrenergic signaling and BMD in separate studies. In my research, we are evaluating miRNAs associated with BB use and BMD using supervised and unsupervised analysis techniques. To investigate potential miRNA-mediated mechanisms, we used the Framingham Heart Study/Osteoporosis sub-study containing data from participants in the Offspring Cohort that underwent clinical exams, dual-energy X-ray absorptiometry (DXA) scans, and miRNA and mRNA profiling of whole blood. Using multiple linear regression and weighted gene co-expression network analysis (WGCNA) we are determining a list of miRNA along with putative mechanisms by which these miRNA may mediate the effect between BB use and BMD. We are also evaluating single nucleotide polymorphism in genes related to osteoporosis and BB use to determine if there is a genetic component that influences the association between BB use and BMD. These analyses provide a starting point to improve our understanding of how BB use may improve BMD in at-risk populations.