Effects of Anti-RANKL Antibody and Zoledronic Acid on Periapical Lesion Development in Mice

Abstract

Introduction

Anti-resorptive drugs are widely used to treat osteoporosis and other systemic bone diseases, though their efficacy for local bone resorption following localized inflammation has not been fully elucidated. We examined the effects of an anti-receptor activator of nuclear factor-κB ligand (RANKL) antibody and the bisphosphonate zoledronic acid (ZOL) on periapical lesion (PL) development in mice.

Methods

Dental pulps of lower first molars in mice were removed, with the exposed dental pulp chambers left open to the oral environment to induce apical periodontitis. An anti-RANKL antibody or ZOL was intraperitoneally injected once per week until postoperative day 21, then micro-computed tomography and histological analyses were performed.

Results

PL enlargement was inhibited by both the anti-RANKL antibody and ZOL in a dose-dependent manner and reduction of inflammatory cell infiltration in apical tissues inhibited periapical bone resorption. The anti-RANKL antibody decreased the number of osteoclasts in periapical tissues, while ZOL suppressed periapical bone resorption with osteoclast numbers maintained. While administration of each of the anti-resorptive drugs increased femoral bone mass, femoral bone mineral density in the PL group was lower as compared to the sham-operated group.

Conclusions

These results suggest that an anti-resorptive drug administered systemically is distributed to areas of local inflammation in the jaw and can prevent PL development.