Language
English
Publication Date
2-2-2025
Journal
Journal of Bone and Mineral Research
DOI
10.1093/jbmr/zjae200
PMID
39673185
PMCID
PMC11789393
PubMedCentral® Posted Date
12-13-2024
PubMedCentral® Full Text Version
Post-print
Abstract
Motivated by studies showing an association between beta blocker (BB) use and positive bone outcomes, a pilot randomized control trial was performed at the Mayo Clinic which randomized postmenopausal women to placebo, propranolol (40 or 80 mg twice daily), atenolol (50 mg/d), or nebivolol (5 mg/d) to determine changes in bone turnover markers (BTMs) and in BMD over 20 wk. Pharmacogenetic effects and microRNA-mediated mechanisms involving beta adrenergic receptor and related genes have previously been found. We sought to validate these effects and discover new candidates in an ancillary study to the pilot clinical trial. We genotyped all participants and performed microRNA (miRNA) sequencing at baseline and at 20 wk for 24 participants from the atenolol or placebo groups. We discovered several variants in ADRB1, ADRB2, and HDAC4 which showed significant pharmacogenetic effects with BMD at multiple sites and with BTMs. Our miRNA results showed a significant treatment effect for miR-19a-3p over time with atenolol use in the low-responder group compared to placebo. Overall, the longitudinal miRNA analysis showed a large number of miRNAs which were up-regulated over the trial in the low responders but not the high responders compared to placebo, of which miR-19a-3p was one example. Finally, we compared the response to atenolol treatment for cardiovascular traits (pulse and blood pressure) with the response for the bone resorption marker, C-terminal telopeptide, and found a largely independent effect. Our results have implications for personalized therapy and for understanding mechanisms of BB treatment effect on bone.
Keywords
Humans, MicroRNAs, Female, Middle Aged, Adrenergic beta-Antagonists, Pharmacogenetics, Bone and Bones, Bone Density, Receptors, Adrenergic, beta-2, Aged, Receptors, Adrenergic, beta-1, Histone Deacetylases, beta blocker, beta adrenergic signaling, osteoporosis, bone mineral density, BMD, pharmacogenetics, pharmacogenomics, microRNA, miRNA
Published Open-Access
yes
Recommended Citation
Lary, Christine W; Atkinson, Elizabeth J; Spillane, Jennifer; et al., "Pharmacogenetic and microRNA Mechanisms of Beta Blocker Use on Bone" (2025). Faculty, Staff and Students Publications. 8400.
https://digitalcommons.library.tmc.edu/baylor_docs/8400