Oxidized-Lipid Signaling and Ferroptosis as Downstream Mechanisms of Titanium-Associated Peri-Implant Bone Loss

Titanium and its alloys remain the dominant materials in oral implantology, but degradation products released through corrosion, tribocorrosion, and wear are biologically active. This critical narrative review examines oxidized-lipid signaling and ferroptosis as candidate downstream mechanisms connecting titanium-associated redox dysregulation with peri-implant bone loss. A targeted literature search of PubMed, Web of Science, and Scopus was updated through 2 August 2026 and integrated evidence from dental peri-implant studies, titanium-particle osteolysis models, and broader skeletal research. Titanium-derived particles can promote mitochondrial and non-mitochondrial reactive oxygen species, membrane phospholipid peroxidation, reactive aldehyde formation, and oxidized-phospholipid signaling. Experimental titanium-particle models demonstrate GPX4 repression and osteoblast ferroptosis, while skeletal studies indicate that ferroptotic dysfunction of osteoblasts and osteocytes can impair mineralization, increase the RANKL/OPG ratio, and favor osteoclastogenesis. Human peri-implant fluid data provide emerging but non-diagnostic evidence, including altered GPX4 and malondialdehyde levels. Specialized pro-resolving mediators may counterbalance the destructive lipid-peroxidation branch. Current evidence supports a biologically plausible and experimentally testable pathway rather than established causation in human dental peri-implant tissues. Direct tissue-level confirmation using redox lipidomics, iron mapping, pathway-specific rescue experiments, and spatial osteoimmune profiling is required.