The extent of surgical trauma may not be a key factor in Medication related Osteonecrosis of the Jaw (MRONJ) development: an in vivo study in the rat model
Objectives: Although the pathogenesis of Medication Related Osteonecrosis of the Jaw (MRONJ) is not fully understood, surgical trauma is thought to play a role. Therefore, the aim of the study was to compare incidence and characteristics of MRONJ following single or two molar tooth extractions in a rat model. Methods: 17 Male Lewis rats were treated with subcutaneous injection of zolendronic acid (ZA), 7.5 µg/Kg) and dexamethasone (Dex), 1 mg/kg), or saline, once a week, for 11 weeks. At three weeks, the first maxillary molar (n=10) or first and second maxillary molars (n=7) were extracted. 8 weeks following tooth extraction, rats were sacrificed and the extraction sites were examined for MRONJ (both clinically and histologically). Results: MRONJ-like lesions were evident in 55.5% of the cases, with impaired healing and exposed bone. In both the control and the multiple extraction ZA/Dex groups, none of the rats showed visible signs of MRONJ. Histological characteristics of MRONJ were found in all rats treated with ZA/Dex (both single and multiple extractions) whereas rats treated with saline showed almost no empty lacunae and necrotic bone. Conclusions: The extent of the surgical field may not be the key factor in MRONJ development in bisphosphonate-treated individuals. The effects of chronic micro-trauma or local infection may play a role and require further investigation.