Overcoming Nuclear Winter: The Cutting-edge Science of Bone Healing and Regeneration in Irradiated Fields

Background: The incidence of cancer worldwide is expected to be more than 22 million annually by 2030. Approximately half of these patients will likely require radiation therapy. Although radiotherapy has been shown to improve disease control and increase survivorship, it also results in damage to adjacent healthy tissues, including the bone, which can lead to devastating skeletal complications, such as nonunion, pathologic fractures, and osteoradionecrosis. Pathologic fractures and osteoradionecrosis are ominous complications that can result in large bone and soft tissue defects requiring complex reconstruction. Current clinical management strategies for these conditions are suboptimal and dubious at best. The gold standard in treatment of severe radiation injury is free tissue transfer; however, this requires a large operation that is limited to select candidates. Methods: With the goal to expand current treatment options and to assuage the devastating sequelae of radiation injury on surrounding normal tissue, our laboratory has performed years of translational studies aimed at remediating bone healing and regeneration in irradiated fields. Three therapeutics (amifostine, deferoxamine, and adipose-derived stem cells) have demonstrated great promise in promoting healing and regeneration of irradiated bone. Results: Amifostine confers prophylactic protection, whereas deferoxamine and adipose-derived stem cells function to remediate postradiation associated injury. Conclusions: These prospective therapeutics exploit a mechanism attributed to increasing angiogenesis and ultimately function to protect or restore cellularity, normal cellular function, osteogenesis, and bone healing to nonirradiated metrics. These discoveries may offer innovative treatment alternatives to free tissue transfer with the added benefit of potentially preventing and treating osteoradionecrosis and pathologic fractures