Deferoxamine reverses radiation induced hypovascularity during bone regeneration and repair in the murine mandible.
BACKGROUND
Deferoxamine (DFO) is an iron-chelating agent that has also been shown to increase angiogenesis. We hypothesize that the angiogenic properties of DFO will improve bone regeneration in distraction osteogenesis (DO) after x-ray radiation therapy (XRT) by restoring the vascularity around the distraction site.


METHODS
Three groups of Sprague-Dawley rats underwent distraction of the left mandible. Two groups received pre-operative fractionated XRT, and one of these groups was treated with DFO during distraction. After consolidation, the animals were perfused and imaged with micro-CT to calculate vascular radiomorphometrics.


RESULTS
Radiation inflicted a severe diminution in the vascular metrics of the distracted regenerate and consequently led to poor clinical outcome. The DFO treated group revealed improved DO bone regeneration with a substantial restoration and proliferation of vascularity.


CONCLUSIONS
This set of experiments quantitatively demonstrates the ability of DFO to temper the anti-angiogenic effect of XRT in mandibular DO. These exciting results suggest that DFO may be a viable treatment option aimed at mitigating the damaging effects of XRT on new bone formation.
Craniofacial Research Laboratory, University of Michigan Medical School, Ann Arbor, MI 48109-0219, USA. afarberg@umich.edu
Aaron S
AS
Farberg
Xi L
XL
Jing
Laura A
LA
Monson
Alexis
A
Donneys
Catherine N
CN
Tchanque-Fossuo
Sagar S
SS
Deshpande
Steven R
SR
Buchman
D000792:Angiography; D000818:Animals; D001861:Bone Regeneration / Q000187:drug effects / Q000528:radiation effects*; D003676:Deferoxamine / Q000494:pharmacology*; D008297:Male; D008334:Mandible / Q000098:blood supply* / Q000187:drug effects* / Q000473:pathology / Q000528:radiation effects; D051379:Mice; D011827:Radiation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014945:Wound Healing / Q000187:drug effects* / Q000528:radiation effects*; D055114:X-Ray Microtomography; D014965:X-Rays
D003676:Deferoxamine