PUBLICATION
Repurposing Acebutolol for Osteoporosis Treatment: Insights From Multi-Omics and Multi-Modal Data Analysis
- Authors
- Liu, D.Y., Shen, H., Greenbaum, J., Yi, Q.R., Liang, S., Zhang, Y., Liu, J.C., Qiu, C., Zhao, L.J., Tian, Q., Su, K.J., Luo, Z., Wu, L., Meng, X.H., Xiao, H.M., Deng, Y., Li, Y., Lovre, D., Fonseca, V., Sanchez, F.L., Tan, L.J., Deng, H.W.
- ID
- ZDB-PUB-250607-2
- Date
- 2025
- Source
- Clinical Pharmacology and Therapeutics : (Journal)
- Registered Authors
- Deng, Yun
- Keywords
- none
- MeSH Terms
-
- Animals
- Bone Density/drug effects
- Bone Density Conservation Agents*/pharmacology
- Bone Density Conservation Agents*/therapeutic use
- Disease Models, Animal
- Drug Repositioning*/methods
- Genome-Wide Association Study
- Humans
- Mendelian Randomization Analysis
- Multiomics
- Osteoporosis*/drug therapy
- Osteoporosis*/genetics
- Signal Transduction/drug effects
- Zebrafish
- PubMed
- 40476595 Full text @ Clin. Pharmacol. Ther.
Citation
Liu, D.Y., Shen, H., Greenbaum, J., Yi, Q.R., Liang, S., Zhang, Y., Liu, J.C., Qiu, C., Zhao, L.J., Tian, Q., Su, K.J., Luo, Z., Wu, L., Meng, X.H., Xiao, H.M., Deng, Y., Li, Y., Lovre, D., Fonseca, V., Sanchez, F.L., Tan, L.J., Deng, H.W. (2025) Repurposing Acebutolol for Osteoporosis Treatment: Insights From Multi-Omics and Multi-Modal Data Analysis. Clinical Pharmacology and Therapeutics. :.
Abstract
Osteoporosis is a common metabolic bone disease with aging, characterized by low bone mineral density (BMD) and higher fragility fracture risk. Although current pharmacological interventions provide therapeutic benefits, long-term use is limited by side effects and comorbidities. In this study, we employed driver signaling network identification (DSNI) and drug functional networks (DFN) to identify repurposable drugs from the Library of Integrated Network-Based Cellular Signatures. We constructed osteoporosis driver signaling networks (ODSN) using multi-omics data and developed DFN based on drug similarity. By integrating ODSN and DFN with drug-induced transcriptional responses, we screened 10,158 compounds and identified several drugs with strong targeting effects on ODSN. Mendelian randomization assessed potential causal links between cis-eQTLs of drug targets and BMD using genome-wide association study data. Our findings indicate four drugs, including Ruxolitinib, Alfacalcidol, and Doxercalciferol, may exert anti-osteoporosis effects. Notably, Acebutolol, a β-blocker for hypertension, has not previously been implicated in osteoporosis therapy. For validation, zebrafish osteoporosis models were established using Dexamethasone-induced bone loss, followed by treatment with Acebutolol hydrochloride and Alfacalcidol. Both compounds demonstrated significant protective effects against osteoporosis-related bone deterioration. Furthermore, a population-based data set, utilizing propensity score matching and analyzed via a generalized linear model, revealed that individuals taking β-blocker drugs exhibited significantly higher BMD than users of other cardiovascular medications. In summary, this study integrates multi-omics approaches, experimental validation, and real-world population data to propose acebutolol as a novel candidate for osteoporosis treatment. These findings warrant further mechanistic studies and clinical trials to evaluate its efficacy in osteoporosis management.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping