Experimental model of osteonecrosis of the jaw in rats treated with zoledronic acid.

We have examined the development of medication-related osteonecrosis of the jaws (MRONJ) in rats with no previous accumulation of zoledronic acid in the mandible. Ten male Wistar rats (weight 350-400g) were anaesthetised with chloral hydrate 450mg/kg intraperitoneally and the first and second mandibular molars on the left side were extracted. The five experimental rats were given six injections of zoledronic acid 0.18mg/kg over the next four weeks (total dose 1.08mg/kg). Two injections were given at once as an intravenous bolus injection (0.36mg/kg). Then rats were given 4 injections (0.18mg/kg) with 1 week interval over the next four weeks, after which they observed for a further four weeks. The five control rats were injected with saline. At the end of the eighth week, the animals were killed by asphyxiation in a carbon dioxide chamber, and their bone structure was visualised using cone-beam computed tomography (CT) and Galaxis software. We then studied the mandibles histopathologically to investigate the incidence of necrosis and infiltration of inflammatory cells. The cone-beam CT images in the experimental group showed deficiencies in the bone structure in the extracted molar area of the lower alveolar ridge. The histological findings in the mandibles of the group given zoledronic acid showed necrosis and infiltration of inflammatory cells, which were not present in the control group. We conclude that the immediate effect of zoledronic acid on the bone tissue during regeneration is an important factor in the development of MRONJ, in addition to the previously reported effects of the duration of treatment with zoledronic acid.