Combined Treatment of Amifostine and Deferoxamine Restores Bone Mineral Beyond Normal Fracture Healing
Abstract
Radiotherapy is a valuable tool in the management of Head and Neck Cancer (HNC)
patients. Despite its usefulness in increasing survival for patients with HNC, the use of
radiotherapy has been known to have detrimental effects to bone.1 Osteoradionecrosis and
pathologic fractures are known to occur in 5%-10% of patients after high dose radiotherapy to
the jaw. Currently there are no therapeutic options known to circumvent the development of
ORN and pathologic fractures in this setting. Radiation is known to cause vascular diminution
and reduction in the number and function of osteocytes, which can ultimately lead to the
devastating sequelae of ORN and pathologic fractures.4.s A combined therapy of Deferoxamine
(DFO)-a vascular augmentation therapy and Amifostine (AMF)-a cellular radioprotectant,
was utilized on a radiation induced non-union rat model to investigate these aberrant effects.
Micro Computed Tomography {JlCT} was used for tissue examination of bone for osteocyte
count, and gross inspection of fractured mandibles after dissection was used to assess for bone
union as outcome measures. A significant restoration of bone volume fraction (BVF) (p = 0.000)
and osteocyte count (Oc) (p = 0.000) was found when comparing radiated fractures to radiated
fractures treated with combination therapy. Further, these metrics were comparable to nonradiated
bone that had undergone fracture repair (BVF-p = 0.746; Oc-p = 0.064), indicating
that normal fracture healing was apparent despite the effects of radiotherapy in treated samples.
Ultimately, on gross inspection, non-radiated fractures exhibited 100% bony union, radiated
fractures exhibited 25% bony union, and radiated fractures with combination therapy exhibited
80% bony union. In conclusion, the combination of DFO and AMF may be a useful clinical
therapeutic strategy in the management of ORN, pathologic fractures and prevention of nonunions
after radiotherapy.