PMID- 38027014
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231201
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 14
DP  - 2023
TI  - Indication and adverse event profiles of denosumab and zoledronic acid: based on 
      U.S. FDA adverse event reporting system (FAERS).
PG  - 1225919
LID - 10.3389/fphar.2023.1225919 [doi]
LID - 1225919
AB  - Objective: To investigate adverse events (AEs) associated with denosumab (Dmab) 
      and zoledronic acid (ZA), compare their association strengths, and explore 
      potential applications to provide clinical reference. Methods: We collected data 
      from FAERS from January 2004 to November 2022 and mined AE signals for Dmab and 
      ZA using ROR values. We compared signal intensity for same AEs and investigated 
      off-label use. We also examined their AEs in adjuvant therapy for breast and 
      prostate cancer. Results: 154,735 reports of primary suspect drugs were analyzed 
      in the FAERS database (Dmab: 117,857; ZA: 36,878). Dmab and ZA had 333 and 1,379 
      AE signals, with 189 overlaps. The AEs of Dmab included death (ROR:3.478), 
      osteonecrosis of jaw (ROR:53.025), back pain (ROR:2.432), tooth disorder 
      (ROR:16.18), bone pain (ROR:6.523). For ZA, the AEs included osteonecrosis 
      (ROR:104.866), death (ROR: 3.645), pain (ROR:3.963), osteonecrosis of jaw (ROR: 
      91.744), tooth extraction (ROR: 142.143). Among overlap signals, Dmab showed 
      higher strength in exostosis of the jaw (ROR: 182.66 vs. 5.769), atypical 
      fractures (ROR: 55.589 vs. 9.123), and atypical femur fractures (ROR:49.824 vs. 
      4.968). And ZA exhibited stronger associations in abscess jaw (ROR: 84.119 vs. 
      11.12), gingival ulceration (ROR: 74.125 vs. 4.827), increased bone formation 
      (ROR: 69.344 vs. 3.218). Additionally, we identified 528 off-label uses for Dmab 
      and 206 for ZA, with Dmab mainly used in prostate cancer (1.04%), breast cancer 
      (1.03%), and arthritis (0.42%), while ZA in breast cancer (3.21%), prostate 
      cancer (2.48%), and neoplasm malignant (0.52%). For Dmab in breast cancer 
      treatment, AEs included death (11.6%), disease progression (3.3%), and 
      neutropenia (2.7%), while for ZA included death (19.8%), emotional disorder 
      (12.9%), osteomyelitis (11.7%). For prostate cancer treatment, Dmab;s AEs were 
      death (8.9%), prostate cancer metastatic (1.6%), renal impairment (1.7%), while 
      ZA;s included death (34.4%), general physical health deterioration (19.9%), and 
      hemoglobin decreased (18.9%). Conclusion: Our analysis of FAERS database provided 
      postmarketing surveillance data and revealed different strengths of reported AE 
      signals between Dmab and ZA in some of their common AEs. It's also worth noting 
      that both drugs have potential off-label applications, which could introduce new 
      AEs. This highlights the necessity for safety monitoring when using Dmab and ZA 
      off-label.
CI  - Copyright (c) 2023 Su, Wu, Zhou, Peng, Zhao, Wang and Li.
FAU - Su, Si
AU  - Su S
AD  - School of Pharmacy, Guangdong Medical University, Zhanjiang, China.
AD  - Department of Pharmacy, Shenzhen People's Hospital (The Second Clinical Medical 
      College, Jinan University; The First Affiliated Hospital, Southern University of 
      Science and Technology), Shenzhen, Guangdong, China.
FAU - Wu, Liuqing
AU  - Wu L
AD  - Longgang Central Hospital of Shenzhen, Shenzhen, Guangdong, China.
FAU - Zhou, Guibao
AU  - Zhou G
AD  - Department of Pharmacy, Shenzhen People's Hospital (The Second Clinical Medical 
      College, Jinan University; The First Affiliated Hospital, Southern University of 
      Science and Technology), Shenzhen, Guangdong, China.
FAU - Peng, Lingling
AU  - Peng L
AD  - Department of Pharmacy, Shenzhen People's Hospital (The Second Clinical Medical 
      College, Jinan University; The First Affiliated Hospital, Southern University of 
      Science and Technology), Shenzhen, Guangdong, China.
FAU - Zhao, Huanzhe
AU  - Zhao H
AD  - Department of Pharmacy, Shenzhen People's Hospital (The Second Clinical Medical 
      College, Jinan University; The First Affiliated Hospital, Southern University of 
      Science and Technology), Shenzhen, Guangdong, China.
FAU - Wang, Xiao
AU  - Wang X
AD  - School of Pharmacy, Guangdong Medical University, Zhanjiang, China.
AD  - Department of Pharmacy, Shenzhen People's Hospital (The Second Clinical Medical 
      College, Jinan University; The First Affiliated Hospital, Southern University of 
      Science and Technology), Shenzhen, Guangdong, China.
FAU - Li, Kuan
AU  - Li K
AD  - Department of Pharmacy, Shenzhen People's Hospital (The Second Clinical Medical 
      College, Jinan University; The First Affiliated Hospital, Southern University of 
      Science and Technology), Shenzhen, Guangdong, China.
LA  - eng
PT  - Journal Article
DEP - 20231101
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC10654638
OTO - NOTNLM
OT  - adverse events
OT  - denosumab
OT  - off-label use
OT  - pharmacovigilance
OT  - zoledronic acid
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2023/11/29 18:41
MHDA- 2023/11/29 18:42
PMCR- 2023/11/01
CRDT- 2023/11/29 17:00
PHST- 2023/05/20 00:00 [received]
PHST- 2023/10/18 00:00 [accepted]
PHST- 2023/11/29 18:42 [medline]
PHST- 2023/11/29 18:41 [pubmed]
PHST- 2023/11/29 17:00 [entrez]
PHST- 2023/11/01 00:00 [pmc-release]
AID - 1225919 [pii]
AID - 10.3389/fphar.2023.1225919 [doi]
PST - epublish
SO  - Front Pharmacol. 2023 Nov 1;14:1225919. doi: 10.3389/fphar.2023.1225919. 
      eCollection 2023.