PRS PSRC Podium Proofs 2016
Russell E. Ettinger, MD,* Alexis Donneys, MD,* Noah S. Nelson, BS,* Jose J. Rodriguez, MD,* Alicia E. Snider, MD,* Kavitha Ranganathan, MD,* Sagar S. Deshpande, BS,* M. Laird Forrest, PhD,† Mark S. Cohen, MD,* Steven R. Buchman, MD*
From the *University of Michigan, Ann Arbor, Mich.; and †University of Kansas, Lawrence, Kans.
PURPOSE: Pathologic fractures and associated nonunions arising in irradiated bone are complex management dilemmas for reconstructive surgeons. We developed an implantable, sustained-release nanoparticle formulation of a known angiogenic small molecule, deferoxamine (DFO) that obviates the need for serial injections of standard DFO. Here, we investigate the efficacy of nano-DFO compared with standard DFO in its ability to improve metrics of mineralization, mechanical strength, and bony union.
METHODS: Rats (n = 44) were divided into 4 groups: fracture, radiated fracture, radiated fracture with standard DFO, and radiated fracture with nano-DFO. Radiated groups received radiotherapy 2 weeks before mandibular osteotomy. The nano-DFO group received implantation of the drug at the time of surgery. After a 40-day healing period, mandibles were assessed for bony union, imaged with micro-computed tomography, and mechanically tested to failure. Analysis of variance was used for comparison (P < 0.05).
RESULTS: We observed decreases in all metrics for the radiation group that were remediated with the addition of both DFO and nano-DFO therapies. For metrics of bone mineral density, total mineral density, bone volume fraction, stiffness, and failure load, there was no difference between the 2 treatments. However, there was a clinically relevant increase in bony unions with nano-DFO therapy that was 24% higher than standard DFO (67% vs 91%).
CONCLUSIONS: Our data demonstrate in vivo efficacy for the mineralization and biomechanical properties of implanted nano-DFO when compared with normal DFO. We support the continued investigation of this promising treatment in its translation for the management of pathologic fractures and associated nonunions after radiotherapy.