Deferoxamine restores callus size, mineralization, and mechanical strength in fracture healing after radiotherapy

Plast Reconstr Surg. 2013 May;131(5):711e-719e. doi: 10.1097/PRS.0b013e3182865c57.


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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Biomechanical Phenomena / drug effects
  • Biomechanical Phenomena / physiology
  • Biomechanical Phenomena / radiation effects
  • Bony Callus / drug effects*
  • Bony Callus / physiology
  • Bony Callus / radiation effects
  • Calcification, Physiologic / drug effects*
  • Calcification, Physiologic / physiology
  • Calcification, Physiologic / radiation effects
  • Deferoxamine / pharmacology*
  • Disease Models, Animal
  • Fracture Healing / drug effects*
  • Fracture Healing / radiation effects
  • Male
  • Mandible / drug effects
  • Mandible / physiology
  • Mandible / surgery
  • Osteotomy
  • Radiation Injuries, Experimental / drug therapy*
  • Radiation Injuries, Experimental / physiopathology
  • Radiotherapy / adverse effects*
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Siderophores / pharmacology
  • Tensile Strength / drug effects
  • Tensile Strength / physiology
  • Tensile Strength / radiation effects


  • Siderophores
  • Deferoxamine