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Background: Osteoporosis and bone density reduction are significant health concerns in elderly populations. While aging is a primary factor, drug-induced bone loss-particularly associated with antiviral agents, proton pump inhibitors (PPIs), and immunomodulatory drugs-has become a growing issue in patients managing multiple conditions. Objective: This study aims to comprehensively assess adverse drug reactions (ADRs) related to bone density reduction and osteoporosis in elderly patients using the FDA Adverse Event Reporting System (FAERS). A specific focus is placed on HIV patients using antiretroviral therapy (ART), alongside an exploration of gender differences and toxicological mechanisms of high-risk drugs. Methods: Data from FAERS (2004-Q2 2025) were analyzed using disproportionality analysis (DPA) to calculate Reporting Odds Ratios (RORs) and 95% confidence intervals (CIs). Toxicological analysis was conducted on high-risk drugs (e.g., Tenofovir Disoproxil) using PubChem, GeneCards, and GO/KEGG pathway enrichment to identify disrupted biological processes. Results: Antiretroviral drugs exhibited the most significant risk signals. For decreased bone density, Emtricitabine/Tenofovir Disoproxil (ROR = 713.48, 95% CI: 648.66-784.79) and Tenofovir Disoproxil (ROR = 665.79, 95% CI: 611.91-724.42) showed extreme associations. For osteoporosis, significant signals were also identified for these antivirals, as well as for Esomeprazole (ROR = 12.23, 95% CI: 11.27-13.28) and Adalimumab (ROR = 2.16, 95% CI: 1.99-2.35). Gender-specific differences indicated men are at higher risk from antiviral drugs, whereas women are more affected by bone metabolic and immunomodulatory regulators. Toxicological analyses suggest these drugs disrupt vitamin D metabolism, calcium homeostasis, and parathyroid hormone (PTH) signaling. Conclusion: Long-term use of antiretroviral drugs, PPIs, and immunomodulators is strongly linked to bone metabolic disorders in the elderly. Although pharmacovigilance studies utilizing FAERS are limited by spontaneous reporting bias and the inability to establish direct causality, these quantitative findings and toxicological insights provide robust real-world evidence for enhancing clinical monitoring and personalized risk management.
Liu et al. (Tue,) studied this question.