Jawbone Changes in Sodium Zoledronic Acid- and Dexamethasone-Treated Rats

Abstract

Previous studies have evaluated bisphosphonate-related osteonecrosis of the jaw (ONJ) after tooth extraction with concurrent administration of bisphosphonate zoledronic acid (ZOL) and steroids. However, details of jawbone changes after administration of ZOL and steroids without tooth extraction remain unclear. In this study, we administered ZOL and dexamethasone (DEX) in rats and compared changes in the jawbone with and without tooth extraction. The right maxillary first molar (M₁) was extracted from 8-week-old rats treated with ZOL, ZOL+DEX or DEX. The right maxillary M₁ region as the extraction sample and the left maxillary M₁ region as the non-extraction sample were compared with macroscopic, radiological, histologic and immunohistochemical examinations. In the extraction samples, we detected incomplete mucosal closure macroscopically and found ONJ on histological examination. In addition, immunohistochemical and three-dimensional analysis of trabecular bone structure showed inhibition of remodeling and angiogenesis in the extraction samples. In the non-extraction samples, we observed inhibition of remodeling, reduced activity of osteoclasts and osteoblasts and suppression of angiogenesis. These findings demonstrate that ONJ can develop under the mucosa with ZOL and DEX treatment, even without invasive procedures. The data suggest that ZOL and DEX can induce ONJ in rats under both invasive and noninvasive conditions because ZOL suppresses osteoclast activity and DEX inhibits remodeling by suppressing osteoblast activity. The results also suggest that surgical stress, such as tooth extraction or bacterial infection, might lead to more severe bisphosphonate-related ONJ.