Oxidative stress and its impact on bone graft integration after oncologic therapy

Abstract

Introduction: Bone tissue regeneration following grafting is a complex biochemical and cellular process that requires balanced osteoblast activity, controlled osteoclast resorption, and adequate vascularization. In oncologic patients, chemotherapy and radiotherapy significantly disrupt systemic redox homeostasis, leading to excessive production of reactive oxygen species (ROS). Elevated oxidative stress may interfere with normal bone remodeling and compromise graft incorporation. The objective of the study was to elucidate the biochemical mechanisms through which oxidative imbalance affects bone graft integration after cancer treatment. Material and methods: A narrative literature review was performed, using 10 articles from 2016- 2026, including data from ScienceDirect, PubMed Central, Biomed Central, MedScape, and others, focusing on experimental and clinical studies evaluating oxidative stress biomarkers, mitochondrial dysfunction, and alterations in bone cell metabolism in patients undergoing oncologic therapy. Molecular pathways related to ROS generation, antioxidant defense systems, and intracellular signaling involved in osteoblast and osteoclast regulation were examined. Results: Increased ROS levels activate intracellular signaling cascades that promote osteoclast differentiation and enhance bone resorption. At the same time, oxidative stress inhibits osteoblast proliferation, reduces collagen type I synthesis, and decreases alkaline phosphatase activity, impairing extracellular matrix formation and mineral deposition. Chemotherapeutic agents induce mitochondrial dysfunction and reduce cellular energy availability, further compromising regenerative capacity. Radiotherapy contributes to vascular damage, reduced osteocyte viability, and persistent inflammatory signaling within bone tissue. Diminished antioxidant defenses, including superoxide dismutase and glutathione-dependent pathways, exacerbate oxidative injury. This biochemical imbalance weakens early graft stabilization and increases the risk of delayed healing or graft failure. Moreover, oxidative stress alters angiogenic signaling pathways, reducing vascular endothelial growth factor (VEGF) expression and impairing neovascularization essential for graft survival. Experimental findings suggest that modulation of oxidative stress may partially restore osteoblastic activity and improve structural graft incorporation. Conclusion: Oxidative stress represents a significant biochemical determinant of impaired bone graft integration in oncologic patients. Targeting redox imbalance may offer supportive therapeutic potential in reconstructive protocols. Further clinical investigations are required to establish evidence-based antioxidant strategies capable of improving transplantation outcomes.