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Prevention of radiation-induced bone pathology through combined pharmacologic cytoprotection and angiogenic stimulation.
- Source :
-
Bone [Bone] 2016 Mar; Vol. 84, pp. 245-252. Date of Electronic Publication: 2015 Dec 23. - Publication Year :
- 2016
-
Abstract
- Pathologic fractures and associated non-unions arising in previously irradiated bone are severely debilitating diseases. Although radiation is known to have deleterious effects on healthy tissue cellularity and vascularity, no clinically accepted pharmacologic interventions currently exist to target these destructive mechanisms within osseous tissues. We utilized amifostine-a cellular radioprotectant-and deferoxamine-an angiogenic stimulant-to simultaneously target the cellular and vascular niches within irradiated bone in a rat model of mandibular fracture repair following irradiation. Rats treated with combined therapy were compared to those undergoing treatment with singular amifostine or deferoxamine therapy, nontreated/irradiated animals (XFx) and non-treated/non-irradiated animals (Fx). 3D angiographic modeling, histology, Bone Mineral Density Distribution and mechanical metrics were utilized to assess therapeutic efficacy. We observed diminished metrics for all outcomes when comparing XFx to Fx alone, indicating the damaging effects of radiation. Across all outcomes, only the combined treatment group improved upon XFx levels, normalized all metrics to Fx levels, and was consistently as good as, or superior to the other treatment options (p<0.05). Collectively, our data demonstrate that pharmacologically targeting the cellular and vascular environments within irradiated bone prevents bone injury and enhances fracture healing.<br /> (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Subjects :
- Amifostine pharmacology
Angiography
Animals
Biomechanical Phenomena drug effects
Bone Density drug effects
Bone Diseases diagnostic imaging
Bone Diseases etiology
Deferoxamine pharmacology
Male
Rats, Sprague-Dawley
Amifostine therapeutic use
Bone Diseases drug therapy
Bone Diseases prevention & control
Cytoprotection drug effects
Deferoxamine therapeutic use
Neovascularization, Physiologic drug effects
Radiation Injuries complications
Subjects
Details
- Language :
- English
- ISSN :
- 1873-2763
- Volume :
- 84
- Database :
- MEDLINE
- Journal :
- Bone
- Publication Type :
- Academic Journal
- Accession number :
- 26723578
- Full Text :
- https://doi.org/10.1016/j.bone.2015.12.051