Bone-related adverse events of hormonal therapy: A pharmacovigilance study based on the Food & Drug Administration Adverse Event Reporting System.
This study highlights a strong association between hormonal therapies and bone-related adverse events, emphasizing the need for monitoring bone health in patients receiving these treatments.
Where it sits
this study against the rest of the degarelix corpusSummary and findings
This study evaluated the association between hormonal therapies and bone-related adverse events using FAERS data. It identified 57 significant bone-related signals, including fractures and osteoporosis, most commonly associated with estrogen receptor-targeted drugs and aromatase inhibitors. The study also explored molecular mechanisms, implicating the Janus kinase signaling pathway.
Abstract
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.
Background
This paper addresses the clinical question of how hormonal therapies impact bone health, particularly focusing on adverse events such as fractures and osteoporosis. Prior research has indicated potential risks associated with hormonal treatments, but comprehensive evaluations using large databases like FAERS are limited. Understanding these associations is crucial for clinicians to monitor and manage the risks of bone-related events in patients undergoing hormonal therapy.
Methods
The study utilized FAERS data to analyze adverse events related to five categories of hormonal therapies. A disproportionality analysis was conducted to identify significant adverse events. Transcriptomic data from Gene Expression Omnibus datasets (GSE147271 and GSE20181) were also analyzed to explore bone-related pathways and differentially expressed genes. The specific n and duration of the analysis were not reported in the abstract.
Results
A total of 57 significant bone-related signals were identified, including 22 Important Medical Events. The most frequently reported adverse events were fractures, osteoporosis, and bone metastases. Estrogen-related adverse events typically occurred after 6 months, while androgen-related events appeared earlier. The study identified key genes such as FOS, JUN, COL1A1, and IGF1, implicating the Janus kinase signaling pathway in bone injury.
Interpretation
The findings suggest a strong association between hormonal therapies and bone-related adverse events, particularly fractures and osteoporosis, which aligns with prior literature indicating risks associated with these treatments. However, the clinical significance of these findings may vary, and the effect sizes were not quantified in the abstract. Limitations include reliance on FAERS data, which may introduce confounding factors such as underreporting or misclassification of events.
Key findings
- 57 significant bone-related signals identified, including 22 Important Medical Events.
- Most commonly reported adverse events were fractures at various sites, osteoporosis, and bone metastases.
- Estrogen-related adverse events typically occurred after 6 months.
- Androgen-related events appeared earlier.
- Key genes identified include FOS, JUN, COL1A1, and IGF1.
Limitations
- Relies on FAERS data, which may be subject to reporting biases.
- Does not establish causation between hormonal therapies and bone-related events.
- No specific n or duration reported for the analysis.