Integrative Analysis of Phthalates and Organophosphates in PM ₂ . ₅ ‐Driven Postmenopausal Osteoporosis: A Triangulated Approach Combining Bibliometrics, Network Toxicology, and Molecular Docking

Objective Phthalates (PAEs) and organophosphate esters (OPEs) contained in atmospheric particulate matter (PM 2 . 5 ) have drawn increasing attention for their potential association with postmenopausal osteoporosis (PMOP). However, their systemic mechanisms of action remain largely unclear. This study aimed to integrate bibliometric analysis, network toxicology, and molecular docking to construct a multidimensional “exposure–target–pathway” network of PM 2 . 5 ‐derived PAEs/OPEs in PMOP and to propose an innovative mechanistic hypothesis. Methods A bibliometric analysis of publications from 2013 to 2024 was first conducted to delineate research trends and identify knowledge gaps. Subsequently, network toxicology was applied to screen common targets of PAEs/OPEs and PMOP, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. A protein–protein interaction (PPI) network was then constructed to identify core targets. Finally, molecular docking was performed to validate the binding affinities between key compounds—di(2‐ethylhexyl) phthalate (DEHP), its active metabolite mono(2‐ethylhexyl) phthalate (MEHP), and triphenyl phosphate (TPHP)—and the hub proteins B‐cell lymphoma 2 (BCL2) and estrogen receptor β (ESR2). Results Bibliometric analysis revealed a paucity of mechanistic studies in this field. Network toxicology identified 122 core targets, with enrichment analyses indicating significant involvement in biological processes such as oxidative stress, inflammatory response, and apoptosis. PPI network analysis highlighted BCL2 and ESR2 as pivotal nodes. Molecular docking confirmed that DEHP, MEHP, and TPHP exhibited strong binding affinities with BCL2 and ESR2. Conclusion This study, for the first time, integrates multidisciplinary approaches to reveal that PAEs/OPEs may disrupt bone homeostasis by interfering with BCL2‐and ESR2‐mediated apoptotic pathways. These findings provide a novel theoretical framework and experimental targets for exploring the environmental etiology of PMOP and underscore the urgent need for mechanistic investigations into specific PM 2 . 5 ‐associated pollutants.