Exploring the Mechanisms Underlying Drug-Induced Fractures Using the Japanese Adverse Drug Event Reporting Database
Fractures occur when bones become fragile and are subjected to external forces as occurring during falls. The use of drugs that increase bone fragility or fall risk increases the risk of fracture. This study investigates drug-induced fractures reported in the Japanese Adverse Drug Event Report (JADE...
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| Format: | Article |
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MDPI AG
2021-12-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/14/12/1299 |
| _version_ | 1827670382572732416 |
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| author | Shinya Toriumi Akinobu Kobayashi Hitoshi Sueki Munehiro Yamamoto Yoshihiro Uesawa |
| author_facet | Shinya Toriumi Akinobu Kobayashi Hitoshi Sueki Munehiro Yamamoto Yoshihiro Uesawa |
| author_sort | Shinya Toriumi |
| collection | DOAJ |
| description | Fractures occur when bones become fragile and are subjected to external forces as occurring during falls. The use of drugs that increase bone fragility or fall risk increases the risk of fracture. This study investigates drug-induced fractures reported in the Japanese Adverse Drug Event Report (JADER) database in patients using 4892 drugs. Atypical femur fracture was the most frequently reported fracture, and 58 other fractures were also reported. Using Volcano plots and multiple logistic regression analysis, we identified the risk factors for drug-induced fractures as being female, of older age, higher body mass index, and using one of 90 drugs. The drug groups significantly associated with drug-induced fractures included bone resorption inhibitors, antiviral drugs, dopaminergic drugs, corticosteroids, and sleep sedatives. Principal component analysis was used to examine the relationship between the use of specific drugs and the site of drug-induced fracture. Bone resorption inhibitors and corticosteroids were associated with atypical femur fractures, jaw fractures, and ulna fractures through an osteoclast-mediated process. Other drugs were found to increase fracture risk via non-osteoclast-mediated mechanisms. These findings suggest that many drugs can result in drug-induced fractures through a variety of mechanisms. |
| first_indexed | 2024-03-10T03:20:14Z |
| format | Article |
| id | doaj.art-3b167f905a364c2e975701dda2f673c5 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-10T03:20:14Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-3b167f905a364c2e975701dda2f673c52023-11-23T10:03:46ZengMDPI AGPharmaceuticals1424-82472021-12-011412129910.3390/ph14121299Exploring the Mechanisms Underlying Drug-Induced Fractures Using the Japanese Adverse Drug Event Reporting DatabaseShinya Toriumi0Akinobu Kobayashi1Hitoshi Sueki2Munehiro Yamamoto3Yoshihiro Uesawa4Department of Medical Molecular Informatics, Meiji Pharmaceutical University, Kiyose 204-8588, JapanDepartment of Pharmacy, National Hospital Organization Kanagawa Hospital, Hadano 257-8585, JapanDepartment of Orthopedic Surgery, National Hospital Organization Kanagawa Hospital, Hadano 257-8585, JapanDepartment of Orthopedic Surgery, National Hospital Organization Kanagawa Hospital, Hadano 257-8585, JapanDepartment of Medical Molecular Informatics, Meiji Pharmaceutical University, Kiyose 204-8588, JapanFractures occur when bones become fragile and are subjected to external forces as occurring during falls. The use of drugs that increase bone fragility or fall risk increases the risk of fracture. This study investigates drug-induced fractures reported in the Japanese Adverse Drug Event Report (JADER) database in patients using 4892 drugs. Atypical femur fracture was the most frequently reported fracture, and 58 other fractures were also reported. Using Volcano plots and multiple logistic regression analysis, we identified the risk factors for drug-induced fractures as being female, of older age, higher body mass index, and using one of 90 drugs. The drug groups significantly associated with drug-induced fractures included bone resorption inhibitors, antiviral drugs, dopaminergic drugs, corticosteroids, and sleep sedatives. Principal component analysis was used to examine the relationship between the use of specific drugs and the site of drug-induced fracture. Bone resorption inhibitors and corticosteroids were associated with atypical femur fractures, jaw fractures, and ulna fractures through an osteoclast-mediated process. Other drugs were found to increase fracture risk via non-osteoclast-mediated mechanisms. These findings suggest that many drugs can result in drug-induced fractures through a variety of mechanisms.https://www.mdpi.com/1424-8247/14/12/1299drug-induced fractureatypical femoral fracturebisphosphonatesdenosumabspontaneous reporting systemJapanese Adverse Drug Event Report (JADER) |
| spellingShingle | Shinya Toriumi Akinobu Kobayashi Hitoshi Sueki Munehiro Yamamoto Yoshihiro Uesawa Exploring the Mechanisms Underlying Drug-Induced Fractures Using the Japanese Adverse Drug Event Reporting Database Pharmaceuticals drug-induced fracture atypical femoral fracture bisphosphonates denosumab spontaneous reporting system Japanese Adverse Drug Event Report (JADER) |
| title | Exploring the Mechanisms Underlying Drug-Induced Fractures Using the Japanese Adverse Drug Event Reporting Database |
| title_full | Exploring the Mechanisms Underlying Drug-Induced Fractures Using the Japanese Adverse Drug Event Reporting Database |
| title_fullStr | Exploring the Mechanisms Underlying Drug-Induced Fractures Using the Japanese Adverse Drug Event Reporting Database |
| title_full_unstemmed | Exploring the Mechanisms Underlying Drug-Induced Fractures Using the Japanese Adverse Drug Event Reporting Database |
| title_short | Exploring the Mechanisms Underlying Drug-Induced Fractures Using the Japanese Adverse Drug Event Reporting Database |
| title_sort | exploring the mechanisms underlying drug induced fractures using the japanese adverse drug event reporting database |
| topic | drug-induced fracture atypical femoral fracture bisphosphonates denosumab spontaneous reporting system Japanese Adverse Drug Event Report (JADER) |
| url | https://www.mdpi.com/1424-8247/14/12/1299 |
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