Regenerate Healing Outcomes in Unilateral Mandibular Distraction Osteogenesis Using Quantitative Histomorphometry

Schwarz, Daniel; Arman, Krikor G.; Kakwan, Mehreen S.; Jamali, Ameen M.; Elmeligy, Ayman; Buchman, Steven R.

doi:10.1097/prs.0b013e3181e3b351

Cited by 8 publications

(12 citation statements)

References 66 publications

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“…8–12 In addition this general radiation protocol has been performed for several years in the department of Radiation Oncology under ULAM and UCUCA approved protocols. 8–16 …”

Section: Methodsmentioning

confidence: 99%

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Amifostine Remediates the Degenerative Effects of Radiation on the Mineralization Capacity of the Murine Mandible

Tchanque-Fossuo

Donneys

Deshpande

et al. 2012

Plastic and Reconstructive Surgery

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Background Although radiotherapy is a cornerstone in head and neck cancer treatment it causes substantial morbidity to the normal adjoining bone. Our specific aim is to assess the radioprotective effect of Amifostine (AMF) therapy on the mineralization of the mandible using micro-computed tomography (μCT). We hypothesize that AMF will safeguard the mandible from radiation-induced disruption of the mineralization process and the associated failure of new bone creation. Methods Male Sprague Dawley rats were randomized into 3 groups: Control (n=8), XRT (n=5) and AMF (n=8). XRT and AMF underwent human bioequivalent radiation of 70Gy in 5 fractions to the left hemimandible. 56 days post-radiation, the hemimandibles were harvested for radiomorphometric analyses. Results AMF exhibited less alopecia, mucositis and weight loss as well as increased cortical density in comparison to XRT. Bone and Tissue Mineral Densities showed statistically significant improvement in AMF versus XRT and no difference was observed between AMF versus Control. Detailed μCT analysis further demonstrated significant differences in the mineralization profile when comparing XRT and AMF. AMF maintained regions of lower mineralization consistent with the preservation of normal remodeling. Conclusion We have successfully demonstrated the ability of AMF pre-treatment to protect the natural mineralization profile of bone. This reflects the capacity of AMF prophylaxis to safeguard the normal surrounding mandible from the impediments of collateral damage imposed by radiation. Further study can now be directed at correlating these findings with the potential use of AMF to prevent the devastating associated morbidities of radiotherapy such as pathologic fractures and osteoradionecrosis.

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“…8–12 In addition this general radiation protocol has been performed for several years in the department of Radiation Oncology under ULAM and UCUCA approved protocols. 8–16 …”

Section: Methodsmentioning

confidence: 99%

“…Rats received subcutaneous injection of Buprenorphine (0.15m/kg) with 10 cc Lactated Ringer solution when showing signs of radiation-induced discomfort and/or pain. 8–16 …”

Section: Methodsmentioning

confidence: 99%

Amifostine Remediates the Degenerative Effects of Radiation on the Mineralization Capacity of the Murine Mandible

Tchanque-Fossuo

Donneys

Deshpande

et al. 2012

Plastic and Reconstructive Surgery

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“…This radiation protocol has been performed for several years at the Department of Radiation Oncology. 5–8 …”

Section: Methodsmentioning

confidence: 99%

“…Subcutaneous infusion of buprenorphine (0.15 m/kg) with 10 cc of lactated Ringer’s solution was given to any rats exhibiting signs of radiation-induced discomfort. 5–8 …”

Section: Methodsmentioning

confidence: 99%

“…The posterior hemimandible was potted first at a depth determined to match the location of the region of interest that has been used by our laboratory in the past to look at distraction osteogenesis. 5–8 Specifically, the region of interest was located 5.1 mm behind the last mandibular molar. The anterior hemimandible was potted next by fully burying the third molar in the potting medium.…”

Section: Methodsmentioning

confidence: 99%

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Dose-Response Effect of Human Equivalent Radiation in the Murine Mandible

Tchanque-Fossuo

Monson

Farberg

et al. 2011

Plastic and Reconstructive Surgery

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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.

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A Histomorphometric Analysis of Radiation Damage in an Isogenic Murine Model of Distraction Osteogenesis

Zheutlin

Deshpande

Nelson

et al. 2015

Journal of Oral and Maxillofacial Surgery

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Purpose The devastation radiation therapy (XRT) causes to endogenous tissue in head and neck cancer (HNC) patients can be a prohibitive obstacle in reconstruction of the mandible, demanding a better understanding of XRT-induced damage and options for reconstruction. Our study investigates the cellular damage caused by radiation in an isogenic murine model of mandibular distraction osteogenesis (DO). We posit that radiation will result in reduced osteocytes, with elevated empty lacunae and immature osteoid. Methods Twenty Lewis rats were randomly assigned to two groups: DO (n=10) and XRT/DO (n=10). Both 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 prior to surgery. Animals were sacrificed on postoperative day 40 and mandibles were harvested and sectioned for histological analysis. Results Bone that underwent radiation revealed a significantly decreased osteocyte count and complementary increase in empty lacunae when compared to non-XRT bone (p=0.019, p=0.000). Additionally, XRT bone demonstrated increased immature osteoid and decreased mature woven bone when compared to non-radiated bone (p=0.001 and p=0.003, respectively). Furthermore, analysis of the ratio of immature osteoid to woven bone volume exhibited a significant increase in the XRT bone, further revealing the devastating damage brought by XRT (p=0.001). Conclusion These results clearly demonstrate the cellular diminution that occurs as a result of radiation. This foundational study provides the groundwork upon which to investigate cellular therapies in an immunoprivileged model of mandibular DO.

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Regenerate Healing Outcomes in Unilateral Mandibular Distraction Osteogenesis Using Quantitative Histomorphometry

Cited by 8 publications

References 66 publications

Amifostine Remediates the Degenerative Effects of Radiation on the Mineralization Capacity of the Murine Mandible

Amifostine Remediates the Degenerative Effects of Radiation on the Mineralization Capacity of the Murine Mandible

Dose-Response Effect of Human Equivalent Radiation in the Murine Mandible

A Histomorphometric Analysis of Radiation Damage in an Isogenic Murine Model of Distraction Osteogenesis

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