Bone-related adverse events of hormonal therapy: A pharmacovigilance study based on the Food & Drug Administration Adverse Event Reporting System.

ObjectiveThis study aimed to evaluate the association between hormonal therapies and bone adverse events using the Food & Drug Administration Adverse Event Reporting System (FAERS) and to explore possible molecular mechanisms.MethodsFAERS data were analyzed for adverse events related to five hormonal therapy drug categories, and disproportionality analysis was used to identify significant adverse events. Transcriptomic data from Gene Expression Omnibus datasets (GSE147271 and GSE20181) were analyzed to identify bone-related pathways and differentially expressed genes.ResultsOverall, 57 significant bone-related signals, including 22 Important Medical Events, were identified, most commonly fractures at various sites, osteoporosis, and bone metastases associated with estrogen receptor-targeted drugs and aromatase inhibitors. Estrogen-related adverse events typically occurred after 6 months, whereas androgen-related events appeared earlier. Transcriptomic analysis identified FOS, JUN, COL1A1, and IGF1 as key genes, implicating the Janus kinase signaling pathway in bone injury.ConclusionThis study demonstrates a strong association between hormonal therapy drugs and bone-related adverse events, particularly fractures and bone cancers. It emphasizes the importance of monitoring bone health and suggests the Janus kinase signaling pathway as a potential therapeutic target for mitigating bone-related adverse events.