ESR1 and osteoporosis: Hallmark gene set analysis showed that these genes were mainly associated with apopos, uv_response_dn, etc. Metascape further confirmed that nicotine may affect osteoporosis by triggering multiple pathways such as cancer pathway, response to exogenous stimuli, hypoxic response, etc. PPI network analysis identified eight core targets: SRC, BCL2, HIF1A, TNF, NFKB1, STAT3, the four proteins with the strongest binding ability (CASP3, ESR1, STAT3, SRC) were analyzed by molecular docking.