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Bone resorption inhibitors, such as bisphosphonates (BPs) and anti-receptor activator of nuclear factor kappa B ligand antibodies (denosumab; Dmab), are used to treat osteoporosis and effectively reduce the risk of fracture. However, medication-related osteonecrosis of the jaw (MRONJ) has been reported as a rare adverse effect. Invasive tooth extraction procedures are reportedly a factor in the development of MRONJ. In this study, we aimed to retrospectively observe and clinically examine the effect of medication status on MRONJ development after tooth extraction in patients receiving drug treatment for osteoporosis.This study was conducted among patients who visited our hospital between December 2015 and December 2021. We collected and analyzed the medical information of patients who underwent dental extractions while using osteoporosis medications, including oral and injectable BPs and Dmab.Among antiresorptive medication users, 40 patients (70 teeth) underwent extraction. The mean duration of BP/Dmab use was 40.4 months, and the mean duration of drug holiday was 6.9 months. MRONJ after tooth extraction was not seen in BP users, but we observed two cases in Dmab users. A significant difference in MRONJ development was confirmed with the use of injectable compared with oral medication administration (odds ratio＝5.01).The use of injectable bone resorption inhibitors was associated with a higher risk of developing MRONJ. The route of administration, duration of medication, and withdrawal period should be carefully considered to prevent MRONJ after tooth extraction.

Objective The engagement of the receptor for advanced glycation end products (RAGE) by AGE or S100 perturbs homeostatic mechanisms and provides a basis for cellular dysfunction in pathological situations. To assess the mechanism of vascular immune reactions in chronic periapical periodontitis, we analysed co-expression of RAGE and AGE or S100 in periapical granulomas. Methods Surgically removed periapical lesions, which had been diagnosed as chronic periodontitis, were inspected histologically using paraffin-embedded sections stained with haematoxylin and eosin. Cryostat sections of the tissues, which were identified histologically as periapical granulomas, were then examined by double immunohistochemistry using polyclonal antibodies raised against human CD34 and monoclonal antibodies specific for human RAGE, AGE or S100. Dual-colour immunofluorescence image analysis was also performed to assess the co-expression of RAGE and AGE or RAGE and S100 by endothelial cells. Results Marked expression of RAGE, AGE, and S100 by CD34 + endothelial cells was noted. Dual-colour immunofluorescence image analysis revealed that the RAGE-expressing endothelial cells co-expressed AGE and S100; however, the number of RAGE–AGE-expressing endothelial cells was significantly higher than that of RAGE–S100-expressing endothelial cells. Conclusions Co-expression of RAGE and AGE by endothelial cells in periapical granulomas is more relevant than that of RAGE and S100. The possible engagement of RAGE and AGE may trigger cellular activation and mediate tissue injury.