Periprosthetic osteolysis remains a major cause of implant failure, driven by inflammatory responses to titanium (Ti) wear particles and ions. Inflammatory bowel disease (IBD), a systemic chronic inflammatory condition, exacerbates bone loss, yet its synergistic effects with Ti ions on periprosthetic osteolysis remain unexplored. Here, we investigated how IBD and Ti ions impair bone-implant integration by disrupting osteogenesis via the PI3K/AKT pathway. A rat model of IBD with localized Ti ion exposure was established, alongside in vitro studies using bone marrow mesenchymal stem cells (BMSCs). Micro-CT and histomorphometry revealed severe trabecular bone loss and reduced bone-implant contact (BIC) in the Ti + DSS group, accompanied by increased osteoclast activity and suppressed osteogenic markers (Runx2/Sp7/OPN). Luminex assays showed elevated pro-inflammatory cytokines (such as CXCL1, CCL5 and CCL20) in bone marrow microenvironment, further amplified by Ti ions. RNA sequencing of BMSCs identified downregulation of osteogenic differentiation genes and inhibition of the PI3K/AKT pathway. In vitro, AKT activation rescued osteogenic differentiation and mineralization in BMSCs exposed to Ti + DSS-conditioned inflammatory factors. These findings demonstrate IBD and Ti ions synergistically exacerbate periprosthetic osteolysis by enhancing osteoclastogenesis and suppressing BMSC osteogenesis via PI3K/AKT signaling. Targeting this pathway may offer therapeutic strategies to improve implant longevity in IBD patients.