Influence of the cumulative effect of zoledronic acid on periodontal microcirculation in rats

Abstract

Purpose: To evaluate the effect of repeated administration of zoledronic acid (ZA) on the development and severity of osteonecrosis of the jaws.

Methods: In the experiment, 36 rats were used, which were divided into 4 groups: group 1 was injected with saline for 6 weeks, group 2 was injected with ZA once, group 3 was injected zoledronic acid for 3 weeks once a week, group 4 was injected with ZA for 6 weeks once a week. While taking medications, the tooth was removed. The volumetric blood flow rate was studied using laser and high-frequency ultrasound Doppler in the area of the periodontium of an extracted tooth in rats with the application of acetylcholine. Bone tissue was examined out using CBCT.

Results: In group 2, there was a violation of blood flow in the mucous membrane, bone microcirculation, but no reliable data was obtained in the bone defect in comparison with group 1. In groups 3 and 4, there was significantly disrupted blood flow. This led to an increase of the osteonecrosis (maximum at the 4th group), which was confirmed by data obtained using CBCT. An inverse relationship was observed between the blood flow of bone tissue and the size of the defect after tooth extraction.

Conclusion: The introduction of ZA in a dose-dependent fashion resulted in impaired endothelial vasodilation and impaired blood flow to extraction sockets. These findings might explain the development of osteonecrosis of the mandible following removal of a first molar.

Keywords: BRONJ; Bisphosphonates; Doppler ultrasonography; Endothelial dysfunction; MRONJ; Zoledronic acid.