An in-depth investigation of NAs-induced osteoporosis adverse events: a real-world, network toxicology and molecular docking analysis
BackgroundNucleoside and nucleotide analogs are one of the mainstays of treatment for chronic hepatitis B, but their effects on bone density are highly controversial.MethodsIn this study, four pharmacovigilance analysis methods and Bonferroni-corrected p-values were used to analyze the FDA Adverse E...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-07-01
|
| Series: | Frontiers in Medicine |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2025.1605024/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849706548267319296 |
|---|---|
| author | Jingkai Di Jingkai Di Shuang Wang Lujia Liu Likun Qi Zijian Guo Yingda Qin Chuan Xiang |
| author_facet | Jingkai Di Jingkai Di Shuang Wang Lujia Liu Likun Qi Zijian Guo Yingda Qin Chuan Xiang |
| author_sort | Jingkai Di |
| collection | DOAJ |
| description | BackgroundNucleoside and nucleotide analogs are one of the mainstays of treatment for chronic hepatitis B, but their effects on bone density are highly controversial.MethodsIn this study, four pharmacovigilance analysis methods and Bonferroni-corrected p-values were used to analyze the FDA Adverse Event Reporting System database to investigate the relationship between adefovir and tenofovir and osteoporosine-related adverse events. In addition, the biological pathways and target proteins were studied by network toxicology and molecular docking techniques.ResultsAdefovir showed signs of adverse skeletal events at the two PT levels of OSTEOPOROSIS and BONE DENSITY DECREASED, while tenofovir showed signs of adverse skeletal events at the five PT levels of BONE DENSITY DECREASED, BONE LOSS, OSTEOPENIA, OSTEOPOROSIS and OSTEOPOROTIC FRACTURE. Furthermore, at the overall SMQ level, positive signals of adverse skeletal events were also valid. Subgroup analysis showed that adefovir was more likely to cause osteoporosis in the elderly and women, while tenofovir exhibited the opposite trend. Furthermore, GO and KEGG analyses indicated that both drugs may jointly promote osteoporosis through pathways such as cell migration, G protein-coupled receptor and Toll-like receptor signaling pathways. Molecular docking technology further reveals that the two drugs can produce pathological effects by binding to osteoporosis-related genes such as ADORA1 and JAK1.ConclusionThis study comprehensively reported the risk and mechanisms of osteoporosis caused by the clinical use of NAs drugs, and provided more detailed recommendations for clinical improvement and prevention of adverse events. |
| format | Article |
| id | doaj-art-c2c57c6f66a6411cab47aab11e4dfe60 |
| institution | DOAJ |
| issn | 2296-858X |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Medicine |
| spelling | doaj-art-c2c57c6f66a6411cab47aab11e4dfe602025-08-20T03:16:10ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2025-07-011210.3389/fmed.2025.16050241605024An in-depth investigation of NAs-induced osteoporosis adverse events: a real-world, network toxicology and molecular docking analysisJingkai Di0Jingkai Di1Shuang Wang2Lujia Liu3Likun Qi4Zijian Guo5Yingda Qin6Chuan Xiang7Department of Orthopedics, Second Hospital of Shanxi Medical University, Taiyuan, ChinaShanxi Provincial Key Laboratory of Bone and Soft Tissue Injury Repair, Taiyuan, ChinaDepartment of Gastroenterology, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, ChinaSchool of Stomatology of Shanxi Medical University, Taiyuan, ChinaSchool of Clinical Medicine, Shanxi Medical University, Taiyuan, Shanxi, ChinaSchool of Clinical Medicine, Shanxi Medical University, Taiyuan, Shanxi, ChinaSchool of Clinical Medicine, Shanxi Medical University, Taiyuan, Shanxi, ChinaDepartment of Orthopedics, Second Hospital of Shanxi Medical University, Taiyuan, ChinaBackgroundNucleoside and nucleotide analogs are one of the mainstays of treatment for chronic hepatitis B, but their effects on bone density are highly controversial.MethodsIn this study, four pharmacovigilance analysis methods and Bonferroni-corrected p-values were used to analyze the FDA Adverse Event Reporting System database to investigate the relationship between adefovir and tenofovir and osteoporosine-related adverse events. In addition, the biological pathways and target proteins were studied by network toxicology and molecular docking techniques.ResultsAdefovir showed signs of adverse skeletal events at the two PT levels of OSTEOPOROSIS and BONE DENSITY DECREASED, while tenofovir showed signs of adverse skeletal events at the five PT levels of BONE DENSITY DECREASED, BONE LOSS, OSTEOPENIA, OSTEOPOROSIS and OSTEOPOROTIC FRACTURE. Furthermore, at the overall SMQ level, positive signals of adverse skeletal events were also valid. Subgroup analysis showed that adefovir was more likely to cause osteoporosis in the elderly and women, while tenofovir exhibited the opposite trend. Furthermore, GO and KEGG analyses indicated that both drugs may jointly promote osteoporosis through pathways such as cell migration, G protein-coupled receptor and Toll-like receptor signaling pathways. Molecular docking technology further reveals that the two drugs can produce pathological effects by binding to osteoporosis-related genes such as ADORA1 and JAK1.ConclusionThis study comprehensively reported the risk and mechanisms of osteoporosis caused by the clinical use of NAs drugs, and provided more detailed recommendations for clinical improvement and prevention of adverse events.https://www.frontiersin.org/articles/10.3389/fmed.2025.1605024/fulladefovirtenofovirosteoporosisG protein-coupled receptorIL-17 |
| spellingShingle | Jingkai Di Jingkai Di Shuang Wang Lujia Liu Likun Qi Zijian Guo Yingda Qin Chuan Xiang An in-depth investigation of NAs-induced osteoporosis adverse events: a real-world, network toxicology and molecular docking analysis Frontiers in Medicine adefovir tenofovir osteoporosis G protein-coupled receptor IL-17 |
| title | An in-depth investigation of NAs-induced osteoporosis adverse events: a real-world, network toxicology and molecular docking analysis |
| title_full | An in-depth investigation of NAs-induced osteoporosis adverse events: a real-world, network toxicology and molecular docking analysis |
| title_fullStr | An in-depth investigation of NAs-induced osteoporosis adverse events: a real-world, network toxicology and molecular docking analysis |
| title_full_unstemmed | An in-depth investigation of NAs-induced osteoporosis adverse events: a real-world, network toxicology and molecular docking analysis |
| title_short | An in-depth investigation of NAs-induced osteoporosis adverse events: a real-world, network toxicology and molecular docking analysis |
| title_sort | in depth investigation of nas induced osteoporosis adverse events a real world network toxicology and molecular docking analysis |
| topic | adefovir tenofovir osteoporosis G protein-coupled receptor IL-17 |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2025.1605024/full |
| work_keys_str_mv | AT jingkaidi anindepthinvestigationofnasinducedosteoporosisadverseeventsarealworldnetworktoxicologyandmoleculardockinganalysis AT jingkaidi anindepthinvestigationofnasinducedosteoporosisadverseeventsarealworldnetworktoxicologyandmoleculardockinganalysis AT shuangwang anindepthinvestigationofnasinducedosteoporosisadverseeventsarealworldnetworktoxicologyandmoleculardockinganalysis AT lujialiu anindepthinvestigationofnasinducedosteoporosisadverseeventsarealworldnetworktoxicologyandmoleculardockinganalysis AT likunqi anindepthinvestigationofnasinducedosteoporosisadverseeventsarealworldnetworktoxicologyandmoleculardockinganalysis AT zijianguo anindepthinvestigationofnasinducedosteoporosisadverseeventsarealworldnetworktoxicologyandmoleculardockinganalysis AT yingdaqin anindepthinvestigationofnasinducedosteoporosisadverseeventsarealworldnetworktoxicologyandmoleculardockinganalysis AT chuanxiang anindepthinvestigationofnasinducedosteoporosisadverseeventsarealworldnetworktoxicologyandmoleculardockinganalysis AT jingkaidi indepthinvestigationofnasinducedosteoporosisadverseeventsarealworldnetworktoxicologyandmoleculardockinganalysis AT jingkaidi indepthinvestigationofnasinducedosteoporosisadverseeventsarealworldnetworktoxicologyandmoleculardockinganalysis AT shuangwang indepthinvestigationofnasinducedosteoporosisadverseeventsarealworldnetworktoxicologyandmoleculardockinganalysis AT lujialiu indepthinvestigationofnasinducedosteoporosisadverseeventsarealworldnetworktoxicologyandmoleculardockinganalysis AT likunqi indepthinvestigationofnasinducedosteoporosisadverseeventsarealworldnetworktoxicologyandmoleculardockinganalysis AT zijianguo indepthinvestigationofnasinducedosteoporosisadverseeventsarealworldnetworktoxicologyandmoleculardockinganalysis AT yingdaqin indepthinvestigationofnasinducedosteoporosisadverseeventsarealworldnetworktoxicologyandmoleculardockinganalysis AT chuanxiang indepthinvestigationofnasinducedosteoporosisadverseeventsarealworldnetworktoxicologyandmoleculardockinganalysis |