Several studies have observed radiologic features of patients taking BP. It has been reported that the use of bone scan can detect symptom-free osteonecrosis in patients treated with BP and the extent and characteristics of osteolytic lesions can be determined using CT and MRI . Rocha et al.  maintained that the change of bone was early confirmed by panoramic radiographs making it easy to diagnose MRONJ. In many kinds of radiological examinations including panoramic radiographs, periapical radiographs, CT, and MRI, it was observed that osteolysis, bone deposition, thickening of lamina dura, and cortical margins when taking BP . In addition, it was reported that patients taking BP showed cortical bone erosion, sequestrum formation, or pathological fracture of the jaw in panoramic radiographs .
Moreover, there have been studies quantitatively evaluating changes of the mandible associated with BP on radiographs. Torres et al. [12, 13] compared the thickness, cross-sectional area, and volume of the mandibular cortical bone with MRONJ patients and normal subjects who did not take BP. As a result, MRONJ patients showed larger values than normal subjects. Also, they compared the thickness of the mandibular inferior cortical bone in panoramic radiographs among patients with MRONJ, patients taking bisphosphonate without MRONJ, and normal subjects. The thickness of the cortical bone was significantly thicker in patients with MRONJ (6.81 ± 1.35 mm) than those without MRONJ (5.44 ± 1.09 mm) and normal subjects (4.79 ± 0.85 mm). According to Hamada et al. , it was observed that MRONJ patients had thicker cortical bone and higher radiodensity of cancellous bone than normal subjects on CT images. In addition, Iwata et al.  measured the thickness of the mandibular buccal and lingual cortical bone in three groups: patients with MRONJ, patients taking osteoporosis medication without MRONJ, and non-osteoporotic group. As a result, they found that the cortical bone of patients with MRONJ was significantly thicker than that of the other groups. But they could not find significant difference between patients taking osteoporosis medicine without MRONJ and normal subjects. On the other hand, according to the measurement of the mandibular cortical bone thickness in our study, there was a significant difference only between MRONJ group and normal group. In other words, it is difficult to distinguish patients taking BP without MRONJ from other groups by cortical bone thickness. Therefore, it is difficult to predict the incidence of MRONJ using only cortical bone thickness on patients taking BP.
It was reported that aging of bone tissue and reduction of bone density begins from 45 years of age and bone loss of the cortical bone occurs mainly from about 65 years old . Also, the cortical bone thickness itself varies depending on individual characteristics, such as the shape of the face, occlusal force, and age . Thus, the size of the jaw and the thickness of the cortical bone can vary from person to person. In addition, Zebaze et al.  found that cortical bone thickness can be changed by intracortical remodeling between the cortical bone and cancellous bone. Therefore, we examined not only merely the thickness of the cortical bone but also the ratio of the cortical bone to total bone in this study. The mandibular cortical bone ratio was measured in patients with MRONJ, patients taking BP without MRONJ, and controls, and the difference between these groups was confirmed. As a result, mandibular cortical bone ratio was significantly larger in patients with MRONJ than in patients taking BP without MRONJ and controls. It was also found that the mandibular cortical bone ratio was significantly higher in the patients taking BP without MRONJ than in the controls, that is, the measurement of the mandibular cortical bone ratio showed a significant difference between all groups.
DM can cause bone quality deterioration through microvascular ischemia, endothelial dysfunction, reduced bone remodeling, osteoblast, and osteoclast apoptosis and induce changes in immune cell function and inflammation. Therefore, DM increases the risk of chronic infection and MRONJ . In this study, mandibular cortical bone ratios were compared according to the presence or absence of DM. When cortical bone ratio was examined in patients with DM in each group, there was no significant difference between the patients with MRONJ and the patients taking BP without MRONJ (Table 4). On the other hand, in patients without DM, there was a significant difference between the patients with MRONJ and the patients taking BP without MRONJ (Table 5). In other words, in patients with DM, cortical bone ratio of the group with MRONJ is similar to that of the group taking BP without MRONJ. These results suggest that patients taking BP without MRONJ are more likely to develop MRONJ in the presence of DM.
Additionally, the correlation between the mandibular cortical bone ratio and age was analyzed. As a result, the ratio decreased with increasing age in all groups, but it did not show any significant correlation. This is because the subjects were confined to 65 years or older, not all ages.
The two groups taking BP (those with MRONJ and those taking BP without MRONJ) were subdivided by administration period (the 4 years standard). The reason why they are divided by administration period based on 4 years standard is that the prevalence of MRONJ in patients taking BP treatment for more than 4 years increased significantly to 0.21% . Then, difference of cortical bone ratio by administration period was analyzed. It was resulted that there was no significant difference between patients with MRONJ and patients taking BP without MRONJ. This may be due to the fact that the number of patients who were precisely examined for the administration period in each group was low, and the administration period was not accurate because it depends on the patient’s statements. In addition, the difference of the administration route would have affected the outcome.
In this study, the cortical bone thickness and ratio were measured near the mental foramen, which was measured from the basal bone, not the alveolar bone where the MRONJ is predominant. There are two reasons why reference point was near the mental foramen. First, most MRONJ patients have the alveolar bone that has already invaded cortical bone destruction or has undergone bone resorption due to poor periodontal status. Accordingly, it is difficult to set a reference point for thickness and ratio measurement. Lastly, when osteoporosis medication is taken, it acts systemically and it is difficult to occur specific cortical bone thickness changes only in specific areas of the mandible.
Previous studies have measured cortical bone thickness in relation to MRONJ, but there was no significant difference between patients taking BP without MRONJ and normal subjects. However, in this study, we could also find significant differences between patients taking BP without MRONJ and normal subjects by using mandibular cortical bone ratio. Therefore, if further research is progressed in the future, it may be used as a predictor of the incidence of MRONJ in patients who must have oral surgery including extraction.