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

Abstract

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.

Meloxicam as a Radiation-Protective Agent on Mandibles of Irradiated Rats

“…According to Nyaruba et al (21) and Wernle et al (22), alterations in bone strength seem to be more related to changes in the trabecular morphology than in the cortical morphology of irradiated bone. Nevertheless, the influence of ionizing radiation on the mechanical properties of bone was not yet fully clarified, as there are conflicting reports in previous studies (11,(21)(22)(23). In addition, the micro-CT images (Fig.…”

Prophylactic administration of Amifostine protects vessel thickness in the setting of irradiated bone

“…Both radiation groups received a previously established fractionated dose of 7 Gy/day for 5 days (35 Gy total), equivalent to a human dose of 70 Gy (20, 21). Following a 56-day recovery period, mandibles were perfused with Microfil, dissected, and imaged with µCT.…”

“…Rat hemimandibles were irradiated using a Philips RT250 orthovoltage unit (250 kV, 15 mA) (Kimtron Medical), fractionating the dose at 7 gray per day over 5 days, for a 35 Gray total, in the Irradiation Core at the University of Michigan Cancer Center (20, 21). Rats were anesthetized using an Isofluorane/Oxygen mixture (2% and 1 L/min), and placed right side down, exposing only the left hemimandible to radiation therapy.…”

Raman spectroscopy delineates radiation-induced injury and partial rescue by amifostine in bone: a murine mandibular model

“…We collaborated with the Experimental Irradiation Core of the University of Michigan Comprehensive Cancer Center to calculate a head and neck cancer human-equivalent dose radiation regimen of 70 Gy total [17]. Fractions were administered once daily over five consecutive days using a Philips RT250 orthovoltage unit (250 kV X-rays, 15 mA; Kimtron Medical, Oxford, CT, USA).…”