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Primary bone cancer treatment often requires large bone resections followed by reconstruction using orthopedic implants, which are usually made of titanium (Ti). In oncologic patients, the bone-implant interface (BII) microenvironment is compromised by adjuvant therapies, such as chemotherapy and radiotherapy, which impair tissue repair and disrupt redox homeostasis. Despite high biocompatibility of Ti implants, their long-term success is challenged by the continuous release of degradation products Ti4+ ions and titanium dioxide (TiO2) nanoparticles, which promote chronic inflammatory and oxidative responses at the BII. Ferroptosis, an iron-dependent cell death characterized by lipid peroxidation primarily driven by an increase in reactive oxygen species, has emerged as an important contributor to understanding peri-implant pathology. Recent studies suggest that ferroptosis is associated with impaired osseointegration by inhibiting bone formation and accelerating bone resorption, leading to uncoupled bone remodeling, periprosthetic osteolysis and aseptic loosening. Therefore, modulating ferroptosis appears to be a potential therapeutic strategy. These strategies include implant surface modification with iron chelation or antioxidant coating, as well as pharmaceutical approaches targeting redox-regulatory pathways, such as glutathione peroxidase 4 (GPX4) and nuclear factor erythroid 2-related factor 2 (Nrf2) modulators. This molecular targeting presents a promising therapeutic avenue to preserve BII and potentially improve long-term implant survival in bone cancer patients. In this mini-review, we summarized the effects of ferroptosis on orthopedic implants, highlighting the potential of ferroptotic-targeting treatment to improve long-term implant outcomes in patients undergoing oncologic reconstruction.
Karbonowski et al. (Mon,) studied this question.