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. 2011 Jul;128(1):114-121.
doi: 10.1097/PRS.0b013e31821741d4.

Dose-response effect of human equivalent radiation in the murine mandible: part I. A histomorphometric assessment

Catherine N Tchanque-Fossuo  1 , Laura A Monson, Aaron S Farberg, Alexis Donneys, Aria J Zehtabzadeh, Elizabeth R Razdolsky, Steven R Buchman
Affiliations

Dose-response effect of human equivalent radiation in the murine mandible: part I. A histomorphometric assessment

Catherine N Tchanque-Fossuo et al. Plast Reconstr Surg. 2011 Jul.

Abstract

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 mandible's 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.

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Figures

Figure 1
Figure 1
Experimental Design and Timeline
Figure 2
Figure 2
Sprague Dawley male rat undergoing left hemimandible radiation. Custom-designed lead shield protecting the remainder of the rat.
Figure 3
Figure 3
Rats demonstrating radiation-induced alopecia at low dose XRT (A), middle dose XRT (B) and high dose XRT (C).
Figure 4
Figure 4
Qualitative Histologic Findings. Digital photograph at 16× magnification showing bone, osteocytes within lacunae and empty lacunae with Gomori Trichrome stain at low dose XRT (A), middle dose XRT (B) and high dose XRT (C).
Figure 5
Figure 5
Number of osteocytes per high power field (HPF) at increasing radiation dosage.
Figure 6
Figure 6
Number of empty osteocytic lacunae per high power field (HPF) at increasing radiation dosage
See this image and copyright information in PMC

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