Abstract: BACKGROUND: Zoledronic acid is a classical bisphosphate bone resorption inhibitor; however, its effect and mechanism on the mandibular alveolar bone metabolism are not clarified.
OBJECTIVE: To study the effects of zoledronic acid on the expression of bone resorption and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome in the mandibular alveolar bone of ovariectomized osteoporosis rats.
METHODS: Thirty-six female Sprague-Dawley rats were randomly divided into three groups (n=12 per group): sham group, osteoporosis group (bilateral ovariectomy), and zoledronic acid group (bilateral ovariectomy, followed by administration of zoledronic acid). Twelve weeks after ovariectomy, the rats in the zoledronic acid group were given subcutaneous injection of 20 μg/kg zoledronic acid, and the corresponding doses of saline were injected subcutaneously in the sham and osteoporosis groups. The rat’s mandibular alveolar bone was separated and removed at 4 weeks after administration. Alveolar bone mass band alveolar bone absorption were observed by Micro-CT, the pathological changes of the alveolar bone were observed using hematoxylin-eosin staining, the number of osteoclasts in alveolar bone was observed by tartrate resistant acid phosphatase staining, the expression of NLRP3 was determined by immunohistochemical technique, and the protein levels of NLRP3, Caspase-1, and interleukin-1β in the alveolar bone were detected using western blot.
RESULTS AND CONCLUSION: Compared with the sham group, the bone trabecular structure was broken in the osteoporosis group, with the emergence of a large number of bone resorption lacunae and uneven surface of the alveolar bone; meanwhile, percent bone volume, trabecular thickness, bone mineral density in alveolar bone were lower, trabecular separation were increased, and the number of osteoclast was significantly increased in the osteoporosis group (P < 0.05). Compared with the osteoporosis group, alveolar bone microstructure in the zoledronic acid group was improved, and the above pathological symptoms were alleviated obviously. Immunohistochemistry staining results showed that the expression level of NLRP3 protein was significantly higher in the osteoporosis group than the sham group (P < 0.05), and the expression of NLRP3 was significantly lower in the zoledronic acid group than the osteoporosis group (P < 0.05). Western blot results indicated that the expression levels of NLRP3, Caspase-1 and interleukin-1β proteins was higher in the osteoporosis group than the sham group, while the protein levels in the zoledronic acid were lower than those in the osteoporosis group (P < 0.05). To conclude, zoledronic acid can effectively inhibit the expression of NLRP3, Caspase-1 and inteleukin-1β in the alveolar bone of osteoporotic rats, and inhibit mandibular alveolar bone resorption by reducing the number of osteoclasts.

Key words: zoledronic acid, ovariectomized rat, alveolar bone, osteoporosis, bone metabolism, osteoclast, nucleotide-binding oligomerization domain-like receptor protein 3 inflammasome