Document Detail


Deferoxamine restores callus size, mineralization, and mechanical strength in fracture healing after radiotherapy.
MedLine Citation:
PMID:  23629110     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Therapeutic augmentation of fracture-site angiogenesis with deferoxamine has proven to increase vascularity, callus size, and mineralization in long-bone fracture models. The authors posit that the addition of deferoxamine would enhance pathologic fracture healing in the setting of radiotherapy in a model where nonunions are the most common outcome.
METHODS: Thirty-five Sprague-Dawley rats were divided into three groups. Fracture, irradiated fracture, and irradiated fracture plus deferoxamine. The irradiated fracture and irradiated fracture plus deferoxamine groups received a human equivalent dose of radiotherapy [7 Gy/day for 5 days, (35 Gy)] 2 weeks before mandibular osteotomy and external fixation. The irradiated fracture plus deferoxamine group received injections of deferoxamine into the fracture callus after surgery. After a 40-day healing period, mandibles were dissected, clinically assessed for bony union, imaged with micro-computed tomography, and tension tested to failure.
RESULTS: Compared with irradiated fractures, metrics of callus size, mineralization, and strength in deferoxamine-treated mandibles were significantly increased. These metrics were restored to a level demonstrating no statistical difference from control fractures. In addition, the authors observed an increased rate of achieving bony unions in the irradiated fracture plus deferoxamine-treated group when compared with irradiated fracture (67 percent and 20 percent, respectively).
CONCLUSIONS: The authors' data demonstrate nearly total restoration of callus size, mineralization, and biomechanical strength, and a threefold increase in the rate of union with the use of deferoxamine. The authors' results suggest that the administration of deferoxamine may have the potential for clinical translation as a new treatment paradigm for radiation-induced pathologic fractures.
Authors:
Alexis Donneys; Salman Ahsan; Joseph E Perosky; Sagar S Deshpande; Catherine N Tchanque-Fossuo; Benjamin Levi; Ken M Kozloff; Steven R Buchman
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Plastic and reconstructive surgery     Volume:  131     ISSN:  1529-4242     ISO Abbreviation:  Plast. Reconstr. Surg.     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-04-30     Completed Date:  2013-07-16     Revised Date:  2014-01-13    
Medline Journal Info:
Nlm Unique ID:  1306050     Medline TA:  Plast Reconstr Surg     Country:  United States    
Other Details:
Languages:  eng     Pagination:  711e-9e     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Biomechanical Phenomena / drug effects,  physiology,  radiation effects
Bony Callus / drug effects*,  physiology,  radiation effects
Calcification, Physiologic / drug effects*,  physiology,  radiation effects
Deferoxamine / pharmacology*
Disease Models, Animal
Fracture Healing / drug effects*,  radiation effects
Male
Mandible / drug effects,  physiology,  surgery
Osteotomy
Radiation Injuries, Experimental / drug therapy*,  physiopathology
Radiotherapy / adverse effects*
Random Allocation
Rats
Rats, Sprague-Dawley
Siderophores / pharmacology
Tensile Strength / drug effects,  physiology,  radiation effects
Grant Support
ID/Acronym/Agency:
CA 125187/CA/NCI NIH HHS; R01 CA125187/CA/NCI NIH HHS; T32-GM008616/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Siderophores; J06Y7MXW4D/Deferoxamine
Comments/Corrections
Comment In:
Plast Reconstr Surg. 2013 Dec;132(6):1080e   [PMID:  24281626 ]
Plast Reconstr Surg. 2013 Dec;132(6):1079e   [PMID:  24281625 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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