The risk of osteonecrosis after apical patency during antiresorptive therapy in an animal model

Abstract

Aim

To evaluate whether performing apical patency (AP) poses a risk for the development of osteonecrosis in rats treated with the antiresorptive drugs Zoledronic Acid (ZA) or Denosumab (DMAB).

Methodology

Forty-two male Wistar rats were divided into six groups according to the medication administered and whether apical patency was performed (n = 7): ZA, ZA-AP, DMAB, DMAB-AP, and the control groups CON and CON-AP. The ZA and ZA-AP groups received 0.125 mg/kg of ZA, while the DMAB and DMAB-AP groups received 0.25 mg/kg of DMAB, both administered via intraperitoneal injection twice a week for 4 weeks. One week after completing drug administration, endodontic access was performed on the distal occlusal fossa of the lower left first molars in all animals. AP was carried out in the distal canal of the ZA-AP, DMAB-AP, and CON-AP groups using a size 10 K-file with the aid of an electronic apex locator, extending beyond the apical foramen. In the other groups, the file was inserted up short of apex as determined by electronic apex locator measurement. Coronal sealing was performed and after 21 days, the animals were euthanized, and visual analysis, micro-CT, and histopathological assessments were conducted to evaluate the presence or absence of osteonecrosis. Statistical analysis was performed using frequency statistics and a GLM multivariate ANOVA model followed by Tukey's test with significance at p < .05.

Results

None of the animals exhibited bone exposure or other clinical signs associated with medication-related osteonecrosis of the jaw. No cortical bone destruction, periosteal reaction, or bone sequestration was observed in the micro-CT or histopathological assessments. Medication significantly influenced some micro-CT parameters (p < .05), while the apical patency alone did not (p > .05). When interacting with medication*apical patency, the ZA-AP group showed a significantly lower percentage of bone volume and bone mineral density compared to the ZA group, a tendency not observed in DMAB groups (p < .05).

Conclusions

Apical patency in rats treated with zoledronic acid or denosumab did not cause osteonecrosis of the jaw, only micro-CT changes in bone microarchitecture that cannot be linked to osteonecrosis in zoledronic acid treated animals.