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The effect of Amifostine prophylaxis on bone densitometry, biomechanical strength and union in mandibular pathologic fracture repair.

AbstractBACKGROUND:
Pathologic fractures (Fx) of the mandibles are severely debilitating consequences of radiation (XRT) in the treatment of craniofacial malignancy. We have previously demonstrated Amifostine's effect (AMF) in the remediation of radiation-induced cellular damage. We posit that AMF prophylaxis will preserve bone strength and drastically reverse radiotherapy-induced non-union in a murine mandibular model of pathologic fracture repair.
MATERIALS AND METHODS:
Twenty-nine rats were randomized into 3 groups: Fx, XRT/Fx, and AMF/XRT/Fx. A fractionated human equivalent dose of radiation was delivered to the left hemimandibles of XRT/Fx and AMF/XRT/Fx. AMF/XRT/Fx was pre-treated with AMF. All groups underwent left mandibular osteotomy with external fixation and setting of a 2.1mm fracture gap post-operatively. Utilizing micro-computed tomography and biomechanical testing, the healed fracture was evaluated for strength.
RESULTS:
All radiomorphometrics and biomechanical properties were significantly diminished in XRT/Fx compared to both Fx and AMF/XRT/Fx. No difference was demonstrated between Fx and AMF/XRT/Fx in both outcomes.
CONCLUSION:
Our investigation establishes the significant and substantial capability of AMF prophylaxis to preserve and enhance bone union, quality and strength in the setting of human equivalent radiotherapy. Such novel discoveries establish the true potential to utilize pharmacotherapy to prevent and improve the treatment outcomes of radiation-induced late pathologic fractures.
AuthorsCatherine N Tchanque-Fossuo, Alexis Donneys, Deniz Sarhaddi, Behdod Poushanchi, Sagar S Deshpande, Daniela M Weiss, Steven R Buchman
JournalBone (Bone) Vol. 57 Issue 1 Pg. 56-61 (Nov 2013) ISSN: 1873-2763 [Electronic] United States
PMID23860272 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Copyright© 2013.
Chemical References
  • Radiation-Protective Agents
  • Amifostine
Topics
  • Amifostine (therapeutic use)
  • Animals
  • Densitometry
  • Fractures, Spontaneous (drug therapy, prevention & control)
  • Male
  • Mandible (drug effects, radiation effects)
  • Radiation-Protective Agents (therapeutic use)
  • Rats
  • Rats, Sprague-Dawley

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