Alteration in Volumetric Bone Mineralization Density Gradation Patterns in Mandibular Distraction Osteogenesis following Radiation Therapy

Self Cite

Objective Descriptions of mandibular distraction osteogenesis for tissue replacement after oncologic resection or for defects caused by osteoradionecrosis have been limited. Previous work demonstrated radiation decreases union formation, cellularity and mineral density in mandibular distraction osteogenesis. The authors posit that intermittent systemic administration of parathyroid hormone will serve as a stimulant to cellular function, reversing radiation-induced damage and enhancing bone regeneration. Methods Twenty male Lewis rats were randomly assigned to three groups: group 1 (radiation and distraction osteogenesis, n = 7) and group 2 (radiation, distraction osteogenesis, and parathyroid hormone, n = 5) received a human-equivalent dose of 35 Gy of radiation (human bioequivalent, 70 Gy) fractionated over 5 days. All groups, including group 3 (distraction osteogenesis, n = 8), underwent a left unilateral mandibular osteotomy with bilateral external fixator placement. Distraction osteogenesis was performed at a rate of 0.3 mm every 12 hours to reach a gap of 5.1 mm. Group 2 was injected with parathyroid hormone (60 μg/kg) subcutaneously daily for 3 weeks after the start of distraction osteogenesis. On postoperative day 40, all left hemimandibles were harvested. Biomechanical response parameters were generated. Statistical significance was considered at p ≤ 0.05. Results Parathyroid hormone–treated mandibles had significantly higher failure load and higher yield than did untreated mandibles. However, these values were still significantly lower than those of nonirradiated mandibles. Conclusions The authors have successfully demonstrated the therapeutic efficacy of parathyroid hormone to stimulate and enhance bone regeneration in their irradiated murine mandibular model of distraction osteogenesis. Anabolic regimens of parathyroid hormone, a U.S. Food and Drug Administration–approved drug on formulary, significantly improve outcomes in a model of postoncologic craniofacial reconstruction.

Section: Discussionsupporting

confidence: 89%

Parathyroid Hormone Therapy Mollifies Radiation-Induced Biomechanical Degradation in Murine Distraction Osteogenesis

Deshpande

Gallagher

Donneys³

et al. 2013

Self Cite

“…Before we established a HEDR, our laboratory demonstrated significant alterations in volumetric bone mineralization patterns in irradiated-distracted murine mandible after a fractionation radiation regimen of a total dose of 36 Gy divided into 10 days. 13 However, we did not found any statistically significant differences in BMD when compared to the control. This confounding result is likely due to the fact that our densitometric analysis was conducted on a much narrower spectrum of HU of mineralization, specifically ranging from 800 to 2000 HU instead of the full mineralization spectrum of 800 to 4000 in our current series.…”

Section: Discussioncontrasting

confidence: 63%

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

Tchanque-Fossuo

Donneys

Deshpande

et al. 2012

Self Cite

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.

“…3 Previous work in our lab has demonstrated significant impairment of new bone formation in the murine mandible after XRT most likely precluding the use of distraction osteogenesis as a viable reconstructive option for HNC patients. 4,5,6 ,7 An ideal XRT regimen would have its greatest effect on the primary target without altering the physiologic properties of adjacent tissues that are essential for adequate recovery and healing. Unfortunately, in HNC treatment, the mandible often falls victim to unintended and unwarranted XRT exposure, hindering its ability to generate new bone and heal.…”

Section: Introductionmentioning

confidence: 99%

Dose-Response Effect of Human Equivalent Radiation in the Murine Mandible: Part I. A Histomorphometric Assessment

Tchanque-Fossuo

Monson

Farberg

et al. 2011

Self Cite

Background Our lab previously demonstrated that radiation significantly alters new bone formation in the murine mandible impeding the use of distraction osteogenesis (DO) as a viable reconstructive option after radiatiotherapy in Head and Neck Cancer (HNC). We hypothesize that the deleterious effects of radiation on regenerate formation results from a dose response (DR) depletion of essential osteogenic cells. Our specific aim is to use quantitative histomorphometry (QHM) to objectively measure the human equivalent DR effects of radiation on the integrity of the mandible’s cellular and tissue composition. Methods 20 Sprague-Dawley rats were randomIzed into three radiation dosage groups: low (5.91Gy), middle (7Gy) and high (8.89Gy) delivered in 5 daily fractions. These dosages approximated 75%, 100%, and 150% respectively of the bioequivalent dose the mandible experiences in the clinical regimen of HNC patients. Hemimandibles were harvested 56 days post-radiation, and stained with Gomori Trichrome. QHM was performed using Bioquant software and analysis with a one-way ANOVA Kruskal-Wallis test. Results Our data revealed a statistically significant diminution in the mean number of osteocytes . We also demonstrated a corresponding significant increase in the mean values of empty lacunae. Both of these QHM changes demonstrated a DR relationship. Conclusion Our study supports our hypothesis that radiation induces a DR depletion in osteocytes and an increase in empty lacunae. These reliable and reproducible metrics can now be utilized to determine the efficacy of therapies aimed at safeguarding the cells essential for optimal bone regeneration and potentially enhance the use of DO in HNC patients.