Ann Arbor, MI, United States
Ann Arbor, MI, United States

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Tchanque-Fossuo C.N.,F7894 Mott Childrens Hospital | Tchanque-Fossuo C.N.,University of Michigan | Monson L.A.,F7894 Mott Childrens Hospital | Monson L.A.,University of Michigan | And 10 more authors.
Plastic and Reconstructive Surgery | Year: 2011

Background: The authors laboratory previously demonstrated that radiation significantly alters new bone formation in the murine mandible, impeding the use of distraction osteogenesis as a viable reconstructive option after radiotherapy in head and neck cancer. The authors hypothesize that the deleterious effects of radiation on regenerate formation results from a dose-response depletion of essential osteogenic cells. The authors specific aim was to use quantitative histomorphometry to objectively measure the human equivalent dose-response effects of radiation on the integrity of the mandibles cellular and tissue composition. Methods: Twenty Sprague-Dawley rats were randomized into three radiation dosage groups: low (5.91 Gy), middle (7 Gy), and high (8.89 Gy), delivered in five daily fractions. These dosages approximated 75, 100, and 150 percent, respectively, of the biological equivalent dose the mandible experiences in the clinical regimen of head and neck cancer patients. Hemimandibles were harvested 56 days after radiation and stained with Gomori trichrome. Quantitative histomorphometry was performed using Bioquant software and analysis with a one-way analysis of variance Kruskal-Wallis test. Results: The authors data revealed a statistically significant diminution in the mean number of osteocytes. The authors also demonstrated a corresponding significant increase in the mean values of empty lacunae. Both of these quantitative histomorphometric changes demonstrated a dose-response relationship. Conclusions: The authors study supports their hypothesis that radiation induces a dose-response depletion in osteocytes and an increase in empty lacunae. These reliable and reproducible metrics can now be used to determine the efficacy of therapies aimed at safeguarding the cells essential for optimal bone regeneration and potentially enhance the use of distraction osteogenesis in head and neck cancer patients. © 2011 by the American Society of Plastic Surgeons.


Donneys A.,University of Michigan | Donneys A.,Ford Motor Company | Tchanque-Fossuo C.N.,University of Michigan | Tchanque-Fossuo C.N.,Ford Motor Company | And 11 more authors.
Plastic and Reconstructive Surgery | Year: 2011

Background: Poor healing after mandibular fracture repair can be a devastating morbidity with significant clinical consequences. Elucidating the vascular response after mandibular fracture may help determine potential areas for therapeutic interventions for nonunions. The authors performed microcomputed tomographic imaging after vessel perfusion to ascertain objective measures of vascular networks. They hypothesized that despite the haversian-based, highly cortical structure of the mandible, the vascular response after fracture healing will return to nearly normal levels soon after bony union, mirroring the results of endochondral, highly trabecular long bones. Methods: Sprague-Dawley rats (n = 12) underwent mandibular osteotomy, and a 2.1-mm fixed gap was set. Animals were euthanized at 40 days after surgery and perfused with Microfil. Specimens underwent microcomputed tomographic analysis for stereologic vascular metrics. Data were compared with nonfractured controls (n = 5). Ninety-five percent confidence intervals and the independent samples t test (p < 0.05) were used to determine statistical differences. Results: Quantitative measures for mandibular fracture versus control revealed similarities in the following vascular metrics: vessel volume fraction (0.028 percent versus 0.032 percent; 95 percent CI, -0.027 to 0.0169 percent), vessel number (0.497 mm versus 0.472 mm; 95 percent CI, -0.884 to 0.975 mm), vessel thickness (0.052 mm versus 0.067 mm; 95 percent CI, -0.037 to 0.008 mm), and vessel separation (2.344 mm versus 2.081 mm; 95 percent CI, -0.752 to 1.278 mm). Conclusions: To the authors' knowledge, this is the first study using microcomputed tomography after perfusion to analyze vascular response following mandibular fracture. Their findings establish quantitative similarities and qualitative differences in vascular response to fracture repair of the highly cortical mandible when compared with the highly trabecular long bone. Copyright © 2011 by the American Society of Plastic Surgeons.


Tchanque-Fossuo C.N.,University of Michigan | Monson L.A.,University of Michigan | Farberg A.S.,University of Michigan | Donneys A.,University of Michigan | And 6 more authors.
Plastic and Reconstructive Surgery | Year: 2011

Background: Despite the widespread use of adjuvant irradiation for head and neck cancer, the extent of damage to the underlying bone is not well understood. However, patients can suffer serious clinical consequences, including pathologic fractures, nonunion, and osteoradionecrosis. The authors' specific aim was to objectively quantify the human equivalent radiation dose-response effect of radiation on the biomechanical properties of the murine mandible. MethodS: Twelve Sprague-Dawley rats were randomized into three radiation dosage groups-low (5.91 Gy), middle (7 Gy), and high (8.89 Gy)-delivered in five daily fractions. The fractionation regimen was used to approximate 75, 100, and 150 percent, respectively, of the bioequivalent dose humans receive in conventional head and neck cancer treatment. Fifty-six days after irradiation, hemimandibles were loaded to failure in a uniaxial tension at 0.5 mm/second. Load displacement curves were analyzed for yield and breaking load, and values were considered statistically significant at p < 0.05. Results: The authors' data demonstrated a statistically significant decrease in the yield and breaking load metrics. The authors' reported averages for low, middle, and high radiation dosages were 162, 136, and 69 N, respectively, for yield; and 215, 211, and 141 N, respectively, for breaking load. Both of these quantitative biomechanical properties were diminished in a dose-response pattern. Conclusions: In this article, the authors report a dose-response effect in the degradation of the biomechanical properties of the mandible after fractionated human equivalent radiation. The authors' findings and model can now be used to formulate therapies aimed at remediating those effects and augmenting bone regeneration and healing after adjuvant radiotherapy in head and neck cancer patients. Copyright © 2011 by the American Society of Plastic Surgeons.

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