Analysis of adverse reaction signals of denosumab combined with vitamin D based on the FAERS database

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Affiliation: Department of Orthopedics, Zhejiang Provincial People's Hospital, Hangzhou 310000, China

Keywords: Denosumab Vitamin D FAERS database Adverse drug events Osteoporosis Signal mining Off-label use Benign giant cell tumor of bone Myalgia

DOI: 10.12173/j.issn.2097-4922.202507083

Reference: SHEN Yang, CHEN Jihang. Analysis of adverse reaction signals of denosumab combined with vitamin D based on the FAERS database[J]. Yaoxue QianYan Zazhi, 2025, 29(11): 1898-1905. DOI: 10.12173/j.issn.2097-4922.202507083.[Article in Chinese]  Copied

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Abstract

Objective To analyze adverse reaction signals from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) associated with combined use of denosumab and vitamin D, and to provide a basis for pharmacovigilance and rational clinical drug use.

Methods Adverse event reports of denosumab, vitamin D and their combination therapy were retrieved from the FAERS database from Q2 2010 to Q1 2025. Signal detection was performed using reporting odds ratio (ROR) and proportional reporting ratio (PRR), and the occurrence time characteristics of adverse drug events (ADE) were analyzed according to Medical Dictionary For Regulatory Activities (MedDRA) version 27.1 system organ classes (SOCs) and preferred terms (PTs) description.

Results A total of 155,720 ADE reports were included, among which 15,534 were related to the combined use of the two drugs. The patients were mainly females (84.4%) and those aged 65~85 years (53.5%). The most common outcome was hospitalization (28.8%), with a median ADE onset time of 179.5 days. A total of 331, 59, and 510 signals were detected in the denosumab monotherapy group, vitamin D monotherapy group, and combined therapy group, respectively. Common signals in the combined therapy group included off, label use, arthralgia, limb pain, back pain, and osteonecrosis of the jaw. Strong signals involved benign giant cell tumor of bone, dental deposits, ulnar fracture, parathyroidectomy, and abnormal serum albumin. Newly identified signals included myalgia, dental disorders, femoral fracture, and poor fracture healing.

Conclusion The adverse reaction signals of combined use of denosumab and vitamin D are more prominent than those of either monotherapy, and elderly females are a high, risk population. Clinically, it is necessary to strengthen risk monitoring, balance the benefits of medication against adverse reactions, and rationally optimize the combined treatment strategy.

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