The Balance between Orthodontic Force and Radiation in the Jawbone: Microstructural, Histological, and Molecular Study in a Rat Model

SIMPLE SUMMARY: Patients with head and neck cancer are frequently treated by radiation, which results in a lifelong risk of damage (necrosis) to the jawbones. Some of the irradiated young patients at a later time in life may be interested in orthodontic treatment for esthetic or functional purposes. We undertook this study in order to investigate changes that occur in irradiated jawbones when mild orthodontic force is applied in a rat laboratory model. We found that one low dose of radiation had negatively affected the jawbones and that these changes were visible in X-ray images as well as in microscopic slides. The irradiated bones seemed to be denser in the X-rays and had fewer cells that usually regulate normal bone turnover, compared to non-irradiated bones. However, when orthodontic force was applied after radiation, the changes in the irradiated bones were largely, but not completely, reversed in both X-rays and microscopy to the point that bone properties were approaching those of non-irradiated, orthodontically treated, bones. The findings of this study indicate that orthodontic force may have a beneficial effect on the maintenance of jawbone vitality after radiation, but additional studies using different time-lags between radiation and orthodontic force and higher radiation doses are warranted to support these findings. ABSTRACT: Irradiation of facial bones is associated with a lifelong risk of osteonecrosis. In a rat model, maxillae were exposed to a single 5 Gy dose of external beam radiation and orthodontic force was applied for 2 weeks on the first maxillary molar; control rats were treated identically without radiation. Tooth movement in irradiated jaws was 30% less than in controls, representing radiation-related damage. Micro-CT, histological, and molecular outcomes of orthodontic tooth movement were studied. Microstructurally, bone parameters (trabecular thickness, bone volume fraction, bone mineral density) were significantly affected by orthodontic force but not by radiation. Histological parameters were influenced only by orthodontic force, especially by an increase in osteoclasts. A molecular study revealed a differential distribution of cells expressing pre-osteoclast markers (RANK+—majority, CD11b+, CD14+—minority), with changes being influenced by orthodontic force (increased CD11b+ and CD14+ cells) and also by radiation (decreased RANK+ cells). The activation status of osteoclasts (TRAP staining) showed an orthodontic-force-related increase, which probably could not fully compensate for the radiation-associated impairment. The overall balance showed that orthodontic force had elicited a substantial microstructural, histological, and functional normalization process in irradiated maxillae but a radiation-induced impact was still conspicuous. Additional studies are needed to validate these findings.