Validation of histologic changes induced by external irradiation in mandibular bone. An experimental animal model

Fenner, Matthias; Park, Jung; Schulz, Norbert S.; Amann, Kerstin; Grabenbauer, Gerhard G.; Fahrig, Antje; Karg, J.; Wiltfang, Joerg; Neukam, Friedrich Wilhelm; Nkenke, Emeka

doi:10.1016/j.jcms.2009.07.011

Cited by 43 publications

(36 citation statements)

References 24 publications

(39 reference statements)

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“…Earlier studies were done to develop an induction model of osteoradionecrosis in animals by causing changes in bone physiology with ionizing radiation (12,(14)(15)(16)(17)(18); however, none of these studies focused at preventing its occurrence. In addition, although other studies evaluated the possible effects of radiation-protective agents on ionizing radiation damage(5-11), they tested the agents on acute complications and none correlated to delayed complications.…”

Section: Discussionmentioning

confidence: 99%

“…In the present study, as in others (12,17), was chosen to use external irradiation, similar to the standard protocol for head and neck radiotherapy. The region chosen for irradiation was the mandible, because it is more susceptible to osteoradionecrosis than the hind limbs in animals (15); thus, lower radiation doses had to be used because the head and neck region has more radiosensitive tissues and a high radiation dose could induce early mortality of the animals (17).…”

Section: Discussionmentioning

confidence: 99%

“…According to the linear-quadratic model (19) and considering the α/β ratio, which quantifies the fractionation radiosensitivity of tissues, equals 2 for bone (12), a single dose of 15 Gy is equivalent to a total dose of about 64 Gy in a regimen with multiple 2 Gy fractions as used in the standard protocol for head and neck radiotherapy. In addition, the total dose of 64 Gy is compatible with the minimum radiation dose (60 Gy) needed to enable the development of Figure 1.…”

Section: Discussionmentioning

confidence: 99%

“…However, unlike those studies, it was chosen to perform it 40 days after the animals received irradiation, a period sufficient to reveal histological changes in bone tissue in mandibles of irradiated rats (12), and because tooth extraction is contraindicated during treatment.…”

Section: Discussionmentioning

confidence: 99%

“…Forty days after delivery of radiation (12), the animals were anaesthetized again and placed in a holder to keep their mouth open for the bilateral extraction of the first molars, which was done using the Hollenback dental instrument (Duflex®, S.S. White, Rio de Janeiro, RJ, Brazil). The animals were killed with an anesthesia overdose, half at 15 days after tooth extraction (n=5) and the other half at 30 days after tooth extraction (n=5).…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2017

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This study evaluated the action of ionizing radiation and the possible radioprotective effect of the non-steroidal anti-inflammatory drug meloxicam on the bone physiology of rat mandibles by assessing the alveolar socket healing and bone strength. Forty male Wistar rats were divided in 4 groups (n=10): control (CG), irradiated (IG), meloxicam (MG), meloxicam irradiated (MIG). A dose of 0.2 mg/kg meloxicam was administered to MG and MIG. After this, IG and MIG were irradiated with 15 Gy radiation dose in the mandible. Forty days after the above procedures, the mandibular first molars were extracted and the animals were killed after 15 or 30 days (n=5). Micro-computed tomography and bending test were used to evaluate alveolar socket healing and bone strength, respectively. At 15 days, bone volume, bone volume fraction and trabecular thickness were higher in the CG and MG than in the IG and MIG; and trabecular separation was higher in the IG compared with the others. At 30 days, there was a difference only in trabecular separation, which was higher in IG than in CG and MG, and MIG did not differ from the others. Bone strength was lower in IG compared with CG and MG, and MIG did not differ from the others. In conclusion, the ionizing radiation affected the bone physiology of rat mandibles, delaying the alveolar socket healing and reducing the bone strength. Moreover, the meloxicam had a positive effect on the trabecular separation in alveolar socket healing and on the bone strength.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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

et al. 2017

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Preventive effects of tonsil‐derived mesenchymal stem cells on osteoradionecrosis in a rat model

et al. 2017

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Micro-CT Analysis of Radiation-Induced Osteopenia and Bone Hypovascularization in Rat

et al. 2015

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Treatment of carcinomas of the upper aerodigestive tract often requires external radiation therapy. However, radiation affects all the components of bone, with different degrees of sensitivity, and may produce severe side effects such as mandibular osteoradionecrosis (ORN). Intraosseous vascularization is thought to be decreased after irradiation, but its impact on total bone volume is still controversial. The aim of this study was to compare intraosseous vascularization, cortical bone thickness, and total bone volume in a rat model of ORN versus nonirradiated rats, using a micro-computed tomography (micro-CT) analysis after intracardiac injection of a contrast agent. The study was performed on 8-week-old Lewis 1A rats (n = 14). Eleven rats underwent external irradiation on the hind limbs by a single 80-Gy dose. Three rats did not receive irradiation and served as controls for statistical analysis. Eight weeks after the external irradiation, all the animals received a barium sulfate intracardiac injection under general anesthesia. All samples were analyzed with the micro-computed tomography system at a resolution of 5.5 μm. The images were later processed to create 3D reconstructions and study vascularization, bone volume, and cortical thickness. Data from irradiated and nonirradiated rats were compared using the Kruskal-Wallis test. No animal died after irradiation. Nineteen irradiated tibias and six nonirradiated tibias were included for micro-CT analysis. The vessel percentage was significantly lower in irradiated bones (p = 0.0001). The distance between the vessels, a marker of vascular destruction, was higher after irradiation (p = 0.001). The vessels were also more altered distally after irradiation (p = 0.028). Cortical thickness was severely decreased after irradiation, sometimes even reduced to zero. Both trabecular and cortical structures were destroyed after irradiation, with wide bone gaps. Finally, both total bone volume (p = 0.0001) and cortical thickness (p = 0.0001) were significantly decreased in irradiated tibias compared to nonirradiated tibias. These results led to multiple spontaneous fractures in the irradiated group, and the destruction of intraosseous vessels observed macroscopically with the radiographic preview. This study revealed the impact of radiation on intraosseous vasculature and cortical bone with a micro-CT analysis in a rat ORN model. Hypovascularization and osteopenia are consistent with the literature, contributing a morphological scale with high resolution. Visualization of the vasculature by micro-CT is an innovative technique to see the changes after radiation, and should help adjust bone tissue engineering in irradiated bone.

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Validation of histologic changes induced by external irradiation in mandibular bone. An experimental animal model

Cited by 43 publications

References 24 publications

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

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

Preventive effects of tonsil‐derived mesenchymal stem cells on osteoradionecrosis in a rat model

Micro-CT Analysis of Radiation-Induced Osteopenia and Bone Hypovascularization in Rat

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