Clinical Use of Deferoxamine in Distraction Osteogenesis of Irradiated Bone

Abstract

The deleterious effects of radiotherapy, including hypovascularity and hypocellularity, have made distraction of irradiated bones challenging. Animal studies, however, have demonstrated adjunctive measures such as the administration of deferoxamine to significantly improve bone regeneration across irradiated distraction gaps. In this report, we demonstrate, for the first time, enhanced bone formation following deferoxamine application in a patient following distraction of a previously irradiated maxilla. CT imaging of the pterygomaxillary buttress on the side of administration revealed significantly increased bone area and density relative to the contralateral buttress. This is the first presentation of clinical deferoxamine use to promote bone formation following irradiated bone distraction and highlights the promise for this adjunctive measure to make outcomes after distraction of irradiated bone more reliable.

Implantable hyaluronic acid-deferoxamine conjugate prevents nonunions through stimulation of neovascularization

“…In a collaboration between our laboratory, and reconstructive surgeons at Stanford University, the clinical repurposing, volumetric dosing and delivery of DFO to facilitate distraction osteogenesis in a young adult patient with maxillary hypoplasia secondary to previous radiotherapy was achieved. 42 The clinical utility of distraction osteogenesis in patients exposed to radiation is currently eschewed due to the prohibitive incidence of nonunions. Nonunion in this setting is thought to result from the paucity of vascular ingrowth provided by irradiated tissues and the unmet high angiogenic metabolic demands incurred by mechanical bone regeneration.…”

Deferoxamine Preconditioning of Irradiated Tissue Improves Perfusion and Fat Graft Retention

“…Another limitation of this study is with DFO dosage and treatment regimen. While these were selected based on previously published studies in other models (15, 17, 18, 31), whether a higher or lower dosage administered more or less frequently would result in increased or decreased vascularity is also unknown. Despite this, following DFO treatment, long-term retention of fat grafts injected into irradiated sites was significantly improved.…”

Nonvascularized Bone Graft Reconstruction of the Irradiated Murine Mandible: An Analogue of Clinical Head and Neck Cancer Treatment

“…Indeed, advancements in mandibular reconstruction are highly translatable and have been successfully demonstrated by our laboratory through proof of concept in humans. 30 The advantages of non-vascularized bone graft transplantation are currently restricted to non-irradiated patient populations. In order to develop strategies to facilitate successful nonvascularized reconstruction in the setting of radiation, small-animal models that reflect clinical techniques in mandibular reconstruction are essential.…”

“…[24][25][26][27][28][29] Notably, translation of the surgical and pharmacologic strategies investigated by our laboratory has been successfully demonstrated in human mandibular reconstruction. 30 This study aims to expand upon surgical approaches currently researched by our laboratory as well as previous literature surrounding small-animal models of craniofacial reconstruction. Specifically, this investigation utilizes the 5mm critical-sized defect defined by Deconde et al 31 to establish a murine model of non-vascularized bone graft reconstruction of segmental mandibular defects using an iliac crest donor site.…”