A Histomorphometric Analysis of Radiation Damage in an Isogenic Murine Model of Distraction Osteogenesis.
OBJECTIVE
The devastation radiation therapy (XRT) causes to endogenous tissue in patients with head and neck cancer can be a prohibitive obstacle in reconstruction of the mandible, demanding a better understanding of XRT-induced damage and options for reconstruction. This study investigated the cellular damage caused by radiation in an isogenic murine model of mandibular distraction osteogenesis (DO). The authors posited that radiation would result in fewer osteocytes, with increased empty lacunae and immature osteoid.


METHODS
Twenty Lewis rats were randomly assigned to a DO group (n = 10) or a XRT/DO group (n = 10). These groups underwent an osteotomy and mandibular DO across a 5.1-mm gap. XRT was administered to the XRT/DO group at a fractionated human equivalent dose of 35 Gy before surgery. Animals were sacrificed on postoperative day 40 and mandibles were harvested and sectioned for histologic analysis.


RESULTS
Bone that underwent radiation showed a significantly decreased osteocyte count and complementary increase in empty lacunae compared with non-XRT bone (P = .019 and P = .000). In addition, XRT bone exhibited increased immature osteoid and decreased mature woven bone compared with nonradiated bone (P = .001 and P = .003, respectively). Furthermore, analysis of the ratio of immature osteoid to woven bone volume exhibited a significant increase in the XRT bone, further showing the devastating damage from XRT (P = .001).


CONCLUSIONS
These results clearly show the cellular diminution that occurs as a result of radiation. This foundational study provides the groundwork on which to investigate cellular therapies in an immuno-privileged model of mandibular DO.
Medical Student, Craniofacial Research Laboratory, Plastic Surgery Section, University of Michigan, Ann Arbor, MI.
Alexander R
AR
Zheutlin
Medical Student, Craniofacial Research Laboratory, Plastic Surgery Section, University of Michigan, Ann Arbor, MI.
Sagar S
SS
Deshpande
Research Fellow, Craniofacial Research Laboratory, Plastic Surgery Section, University of Michigan, Ann Arbor, MI.
Noah S
NS
Nelson
Resident, Craniofacial Research Laboratory, Plastic Surgery Section, University of Michigan, Ann Arbor, MI.
Yekaterina
Y
Polyatskaya
Research Fellow, Craniofacial Research Laboratory, Plastic Surgery Section, University of Michigan, Ann Arbor, MI.
Jose J
JJ
Rodriguez
Research Fellow, Craniofacial Research Laboratory, Plastic Surgery Section, University of Michigan, Ann Arbor, MI.
Alexis
A
Donneys
Professor in Plastic Surgery, Craniofacial Research Laboratory, Plastic Surgery Section, University of Michigan, Ann Arbor, MI. Electronic address: sbuchman@med.umich.edu.
Steven R
SR
Buchman
D000818:Animals; D002452:Cell Count; D004195:Disease Models, Animal; D008297:Male; D008334:Mandible / Q000473:pathology / Q000528:radiation effects / Q000601:surgery*; D010011:Osteocytes / Q000473:pathology / Q000528:radiation effects; D019857:Osteogenesis, Distraction; D011832:Radiation Injuries / Q000473:pathology* / Q000601:surgery; D051381:Rats; D011917:Rats, Inbred Lew