Age-dependent impact of Zoledronic acid on periodontal structures under orthodontic loading

Objectives This study aimed to evaluate zoledronic acid (ZOL) induced alterations in the alveolar bone, periodontal ligament, and cementum under orthodontic forces in mice of different ages, focusing on the early and late half-life of ZOL administration. Methods Juvenile (6-week; n = 30) and adult (12-week; n = 20) mice (C57BL/6J) were divided into five groups, with three groups receiving a single ZOL dose. A 0.35 N orthodontic force was applied 1 and 12 weeks after ZOL administration. Alveolar bone, cementum, periodontal ligament response, osteoclast activity, calcium and 1,25(OH)2D3 levels were assessed at 12 h and 12 weeks after force application. Results ZOL reduced tooth displacement and osteoclast counts in the adult and juvenile (latency phase of medication) groups compared to the juvenile control group (P < .05). The thickness of the periodontal ligament and number of blood vessels decreased moderately in adult mice and slightly in juveniles (P < .05), particularly in the ZOL-treated groups. Cementum resorption and alveolar crest irregularities were observed in all the ZOL-treated groups. Juvenile mice that underwent force application 12 weeks after ZOL administration exhibited responses similar to those observed in adult mice. Limitations This study demonstrated that the periodontal ligament and alveolar bone of juvenile and adult mice respond differently to ZOL treatment. However, the mechanisms underlying these differential effects remain unclear, highlighting the need for further investigation of bone remodeling markers to better understand the impact of ZOL during both the active and latency phases in young and adult subjects. Conclusions ZOL intake influenced the alveolar bone, periodontal ligament, cementum, blood vessel count, and tooth displacement under orthodontic force. The extent of these changes was age dependent, with distinct effects observed in juvenile and adult mice. Juvenile mice analyzed in the latency phase of medication exhibited behaviors resembling those of adult mice.