Prevention of radiation-induced bone pathology through combined pharmacologic cytoprotection and angiogenic stimulation.

Autor: Donneys A; University of Michigan, Ann Arbor, MI, USA., Nelson NS; University of Michigan, Ann Arbor, MI, USA., Perosky JE; University of Michigan, Ann Arbor, MI, USA., Polyatskaya Y; University of Michigan, Ann Arbor, MI, USA., Rodriguez JJ; University of Michigan, Ann Arbor, MI, USA., Figueredo C; University of Michigan, Ann Arbor, MI, USA., Vasseli CA; University of Michigan, Ann Arbor, MI, USA., Ratliff HC; University of Michigan, Ann Arbor, MI, USA., Deshpande SS; University of Michigan, Ann Arbor, MI, USA., Kozloff KM; University of Michigan, Ann Arbor, MI, USA., Buchman SR; University of Michigan, Ann Arbor, MI, USA. Electronic address: sbuchman@med.umich.edu.
Jazyk: angličtina
Zdroj: Bone [Bone] 2016 Mar; Vol. 84, pp. 245-252. Date of Electronic Publication: 2015 Dec 23.
DOI: 10.1016/j.bone.2015.12.051
Abstrakt: 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.
(Copyright © 2015 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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