The preliminary F-18 fluoride and F-18 FDG PET study of rat BRONJ model using other types of bisphosphonate

Objectives The aim of this preliminary study was to evaluate the metabolic change of F18 FDG- and 18F fluoride PET/CT in rat bisphosphonate-related osteonecrosis of the jaw (BRONJ) model using other types of bisphosphonate.

Methods Rats were allocated into 3 groups: (1) rats treated with zoledronic acid (ZA), (2) rats treated with alendronate, (3) control rats. Following 4 week period of Tx, upper right molars were extracted under anesthesia. After 4 weeks from the extraction, the rats were clinically examined and underwent animal PET/CT with F-18 fluoride and F-18 FDG. Then they were sacrificed and histological analysis was performed.

Results In F-18 FDG PET/CT of all groups, the glucose metabolism of extraction site was higher than those of contralateral (unwounded) site. Furthermore, ZA groups had 1.4 times high SUV ratio of ipsilateral lesion- to contralateral non-lesion site than in control groups (p < 0.05). Alendronate groups had high tendency of ipsilateral lesion- to contralateral non-lesion site than in control groups though there was no significant difference (1.40 vs. 1.25, p > 0.05). F-18 fluoride PET/CT showed that ZA groups had significantly lower SUV ratio of ipsilateral lesion- to contralateral non-lesion site than in control groups and alendronate groups (0.84 vs. 0.93 and 0.88; both of them p < 0.05, respectively). However, alendronate groups didn't. Rats treated with ZA for 4 week period developed high incidence of BRONJ-like lesions following extraction of maxillary molars, whereas control rats underwent predictable healing with rapid epithelialization in tooth extraction site. Furthermore, number of exposed necrotic bone sequestra and prevalence of pseudoepitheliomatous hyperplasia were higher in ZA groups than in other groups.

Conclusions In our preliminary study, other types of bisphosphonate showed different bony uptake and glucose metabolism ratio in the 4 weeks after tooth extraction which could be related with variable incidences of rat BRONJ models.

Research Support This research was funded by National Research Foundation (2012R1A1A1012913) of south Korea.