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. 2025 Jul 24:13:1630412.
doi: 10.3389/fpubh.2025.1630412. eCollection 2025.

Sex differences in drug-induced osteoporosis: a pharmacovigilance study based on the FAERS database

Lu Liu #  1 , Yongjia Song #  1 , Xiaoyu Liu  1 , Bangguo Song  1 , Min Song  1
Affiliations

Sex differences in drug-induced osteoporosis: a pharmacovigilance study based on the FAERS database

Lu Liu et al. Front Public Health. .

Abstract

Background: Osteoporosis is a prevalent condition globally, often linked to a significant risk of fractures. Drug-induced osteoporosis (DIOP) is an increasingly recognized adverse effect of various medications, but the sex-specific risks and time-to-onset patterns remain inadequately understood. Addressing these gaps in knowledge is critical to improving patient safety and pharmacovigilance.

Objective: This study aimed to explore sex-related differences in DIOP, identify high-risk medications, and assess the onset patterns of osteoporosis-related adverse events by analyzing data from the FDA Adverse Event Reporting System (FAERS) and validating the findings using the Canada Vigilance Adverse Reaction Online Database (Canada Vigilance ADR).

Methods: We analyzed adverse event reports from the FAERS database covering the period from Q1 2004 to Q4 2024. Drugs were standardized using the RxNorm drug terminology system, and adverse events were matched to MedDRA 27.1. Disproportionality analysis was conducted using Reporting Odds Ratio (ROR), Multi-item Gamma Poisson Shrinker (MGPS), and Bayesian Confidence Propagation Neural Network (BCPNN) methods. To validate our findings, we performed external validation using the Canada Vigilance ADR database. Stratified analyses by sex were performed to assess differences in drug-osteoporosis associations.

Results: A total of 236,928 osteoporosis-related reports were identified, with 64.6% of the reports coming from females. We identified 68 drugs associated with DIOP, including 15 male-specific and 26 female-specific potential risk drugs. Notable drugs such as tenofovir disoproxil and esomeprazole were linked to both sexes. Drugs like upadacitinib exhibited early-onset failure patterns, while others like tenofovir demonstrated cumulative risk patterns over prolonged use. External validation with the Canada Vigilance ADR confirmed 32 drugs with potential osteoporosis risks.

Conclusions: This study highlights important sex-specific differences in the risk of drug-induced osteoporosis and underscores the need for targeted pharmacovigilance strategies. The findings contribute to a more personalized approach to drug safety, promoting more informed decision-making regarding medication use in osteoporosis-prone populations.

Keywords: BCPNN; FAERS; drug-induced osteoporosis; mGPS; pharmacovigilance; sex-specific risk; time-to-onset analysis.

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Conflict of interest statement

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.

Figures

Flowchart showing the analysis of FAERS data from 2004 to 2024 for epileptic seizures. It includes divisions by total, male, and female populations, each with subcategories for drugs and reactions. Screening focuses on drug-induced osteoporosis. Categories include clinical characteristics, signal detection, stratification, and time-to-onset analysis. Terminology follows MedDRA 27.1 standards.
Figure 1
Flow chart of drug-related osteoporosis signal mining. SMQ, standardized MedDRA query; DEMO, demographic information; DRUG, drug information; REAC, reaction information.
Line graph with blue points connected by a line, showing a generally increasing trend. A red dotted trend line is overlaid, represented by the equation y = 0.5372x2 - 1076.2x, with an R2 value of 0.9185, indicating a strong fit.
Figure 2
Number of annual reports of drug-related osteoporosis.
Bar chart illustrating the number of cases associated with various drugs. Tenofovir disoproxil has the highest count at 10,924 cases, with a reporting odds ratio (ROR) of 86.07. Lenalidomide follows with 5,834 cases (ROR 1.33). Other drugs listed include Esomeprazole, Interferon Beta-1A, and Tofacitinib, with descending case numbers and varying RORs. The chart highlights the relationship between drug names and their associated case numbers alongside ROR values.
Figure 3
Top 30 dangerous drugs for drug-induced osteoporosis.
Two violin plots display the time to event analysis for six drugs in panels A and B. Panel A shows Adefovir, Esomeprazole, Tafamidis, Tenofovir Disoproxil, and Upadacitinib. Panel B includes Esomeprazole, Ibrutinib, Tenofovir Disoproxil, Tocilizumab, and Upadacitinib. Vertical axes represent time in days, with wider sections of each violin indicating more frequent values. Each drug is color-coded for distinction.
Figure 4
Heat map of osteoporosis risk drugs from the analysis of FAERS and CVAROD.
Two violin plots titled “Time to Event Analysis” compare different drugs. Plot A includes Adefovir, Esomeprazole, Tafamidis, Tenofovir Disoproxil, and Upadacitinib. Plot B includes Esomeprazole, Ibrutinib, Tenofovir Disoproxil, Tocilizumab, and Upadacitinib. Each drug is represented by a distinct color, showing the distribution of time to event in days.
Figure 5
Violin diagram of drug induction time of the first five danger signals of men and women. (A) Male danger signal drugs; (B) Female danger signal drugs.
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