Osteonecrosis of the Jaw in the United States Food and Drug Administration's Adverse Event Reporting System (FAERS).
Osteonecrosis of the jaw (ONJ) is a serious adverse drug event that was initially reported with intravenous bisphosphonates (BPs) and more recently with other classes of drugs such as receptor activator of NF-κB ligand (RANKL) inhibitor, antiangiogenic agents, and mammalian target of rapamycin (m-TOR) inhibitors. The purpose of this study is to analyze the ONJ cases and the associated drugs in the US Food and Drug Administration's adverse event reporting system (FAERS). The FAERS database was queried for the adverse drug events reported from the first quarter of 2010 to the first quarter of 2014. The reporting odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for each queried drug. A total of 17,119 unique ONJ cases were identified. In the overall analysis, the drugs with the highest reporting ORs were BPs: pamidronate (OR = 498.9), zoledronate (OR = 171.7), and alendronate (OR = 63.6), whereas denosumab had lower ORs than all the BPs except for etidronate. The antiangiogenic and m-TOR inhibitors had the lowest ORs. In cancer patients who were treated for prevention of skeletal-related events (SREs), the reporting ORs for zoledronate and denosumab were 125.2 and 4.9, respectively. In patients with osteoporosis, the ORs were 1.1 (1.0-1.18) for zoledronate and 0.63 (0.56-0.70) for denosumab, respectively. Our analysis of the FAERS database showed that the intravenous BPs were associated with the highest risk for ONJ, RANKL inhibitor was associated with risk comparable to BPs used for osteoporosis such as etidronate, and the antiangiogenic agents and m-TOR inhibitors were associated with the lowest risk for ONJ. The high risk for ONJ with zoledronate and denosumab was mainly observed in those who were treated for prevention of SREs, whereas there was limited evidence for such risk in those who were treated for osteoporosis.
Department of Pharmaceutics and Center for Pharmacometrics and System Pharmacology, College of Pharmacy, University of Florida, Orlando, FL, USA.
Xiaoyan
X
Zhang
Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Gainesville, FL, USA.|Center for Pharmacogenomics, College of Pharmacy, University of Florida, Gainesville, FL, USA.
Issam S
IS
Hamadeh
Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Gainesville, FL, USA.
Shuang
S
Song
Department of Oral Medicine, College of Dentistry, University of Florida, Gainesville, FL, USA.
Joseph
J
Katz
Department of Medicine, College of Medicine, University of Florida, Gainesville, FL, USA.
Jan S
JS
Moreb
Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Gainesville, FL, USA.|Center for Pharmacogenomics, College of Pharmacy, University of Florida, Gainesville, FL, USA.
Taimour Y
TY
Langaee
Department of Pharmaceutics and Center for Pharmacometrics and System Pharmacology, College of Pharmacy, University of Florida, Orlando, FL, USA.
Lawrence J
LJ
Lesko
Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Gainesville, FL, USA.|Center for Pharmacogenomics, College of Pharmacy, University of Florida, Gainesville, FL, USA.
Yan
Y
Gong
D016907:Adverse Drug Reaction Reporting Systems; D000368:Aged; D000369:Aged, 80 and over; D059266:Bisphosphonate-Associated Osteonecrosis of the Jaw / Q000453:epidemiology* / Q000378:metabolism / Q000473:pathology; D016208:Databases, Factual; D004164:Diphosphonates / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000188:drug therapy / Q000453:epidemiology / Q000378:metabolism; D014481:United States; D014486:United States Food and Drug Administration
D004164:Diphosphonates
ANTIANGIOGENIC AGENTS; BISPHOSPHONATES; FAERS; OSTEONECROSIS OF THE JAW; RANKL INHIBITORS