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Deferoxamine Restores Callus Size, Mineralization, and Mechanical Strength in Fracture Healing after Radiotherapy

Donneys, Alexis M.D., M.S.; Ahsan, Salman B.S.; Perosky, Joseph E. M.S.; Deshpande, Sagar S. B.S.; Tchanque-Fossuo, Catherine N. M.D., M.S.; Levi, Benjamin M.D.; Kozloff, Ken M. Ph.D.; Buchman, Steven R. M.D.

Plastic & Reconstructive Surgery: May 2013 - Volume 131 - Issue 5 - p 711e–719e
doi: 10.1097/PRS.0b013e3182865c57
Experimental: Original Articles

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.

Ann Arbor, Mich.

From the Plastic Surgery Section, Craniofacial Research Laboratory, and the Department of Orthopedic Surgery, Orthopedic Research Laboratory, University of Michigan.

Presented at the 57th Annual Meeting of the Plastic Surgery Research Council, in Ann Arbor, Michigan, June 14 through 16, 2012.

Disclosure: The authors have no financial interest to declare in relation to the content of this article.

Received for publication September 11, 2012; accepted November 14, 2012.

University of Michigan Medical School, Pediatric Plastic Surgery Section, 4-730 C.S. Mott Children’s Hospital, 1540 E. Hospital Drive, Ann Arbor, Mich. 48109, sbuchman@med.umich.edu

©2013American Society of Plastic Surgeons