Combination Therapy Preserves Distraction Osteogenesis as a

Method of Irradiated Bone Regeneration

Jeremy Lynn, Kevin Urlaub, Noah Nelson, Yekaterina Polyatskaya MD, Steven Buchman MD

Plastic Surgery Section and Craniofacial Research Laboratory

University of Michigan

Results

Background
Radiation is widely used as treatment for HNC patients, but invites various acute and chronic
side effects such as diminished healing ability of irradiated bone and subsequent pathological
fractures.

Yield Load
80

100

*
90

70

80

Complications due to radiation in HNC patients place craniofacial reconstruction in high demand
but leave reconstructive surgeons few or no options.

60

70

60

50

Our research aims to improve the viability of Distraction Osteogenesis as a method of bone
reconstruction following radiotherapy, therefore offering a top tier reconstructive option to
surgeons and HNC patients alike.

Failure Load

40

50

40

30

30
20
20

Hypothesis

10

10

0
DO

We hypothesize that the radioprotective properties of amifostine and the angiogenic

potential of deferoxamine will function cooperatively to further improve biomechanical
metrics and union rates following radiotherapy and subsequent distraction osteogenesis.

The groups receiving radiation were administered a fractionated, human-equivalent dose of

35Gy over 5 days, comparable to 70Gy in humans.

DFO

DO

XDO

AMF

DFO

Combined

DFO

Combined

Bony Union Rate

100

900

90

80

70

600

60

700

500

50

400

40

300

30

200

20

100

10

0
DO

XDO

AMF

DFO

Combined

DO

XDO

AMF

Figure 2. Graphs of the biomechanical metrics and bony union rates of the five groups tested.

Rats received a mandibular osteotomy and external fixation device during surgery.
AMF was injected immediately prior to XRT and DFO was injected directly into the fracture site
every other day starting POD 4.

Combined

1000

N/mm

Sprague Dawley rats (n=58) were divided into five groups: non-irradiated distraction (DO),
radiated distraction (XDO), radiated distraction with amifostine (AMF), radiated distraction with
deferoxamine (DFO), and radiated distraction with both therapies (Combined).

AMF

Stiffness

800

Methods

XDO

Condyle

Molars

Incisor

DO

XRT/DO

DFO

Combined

Mandibles were potted and loaded to failure to test biomechanical strength (yield load, failure
load and stiffness)

AMF

Figure 1. Experimental timeline represents sequence and timing of therapies and procedures.

Figure 3. CT images exemplify mineralized bone in the ROI upon dissection.

Conclusions

This combined therapy has immense potential in the clinical cases of over 50,000 head and neck cancer patients each year. A
combined AMF/DFO treatment preserves DO as a viable method of bone regeneration following radiotherapy, therefore filling
the current void of reconstructive options for HNC patients and reconstructive surgeons. Additional metrics of bone healing
will be investigated in the future to further support the benefits of a combined therapy.

Acknowledgements
This work was supported by NIH R01
CA 125187-06 to SR Buchman
The authors thank Yekaterina
Polyatskaya, Noah Nelson, and Steven
Buchman for mentorship and support