Lansoprazole Delays Extraction Sockets Healing in Bisphosphonate-Medicated Mice

Objectives: Developing Medication / Anti-resorptive agents / Bisphosphonate -related osteonecrosis of the jaw (ONJ) is a rare but potentially severe adverse effect in patients using anti-resorptive drugs. The Japanese Allied Committee on Osteonecrosis of the Jaw proposed several risk factors including antiresorptive agents, systemic, congentl, lifestyle and co-administered agents. Whereas this position paper mentioned that these risk factors are including hypothesis without robust medical evidence. In 2017, a large-scale cohort study targeting osteoporosis patients in Denmark was reported. It suggested that risk of surgically treated Bisphosphonate-related ONJ (BRONJ) was higher in patients with use of Proton Pomp Inhibitors (PPIs). Here, we evaluate the impact of co-administration of Bisphosphonate and PPIs on the healing of extraction sockets in mice.
Methods: We used zoledronic acid (ZA) as bisphosphonate, and Lansoprazole (LP) as PPI in this study. Six-week-old female C57BL/6J mice were treated with ZA intravenously twice in a week and/or LP intraperitoneally for 3 consecutive days followed by a 1-day off, for 3 weeks. After 1week of starting the animal experiment, tooth extraction was carried out in all groups. Micro CT scans were carried out to evaluate the healing of extraction sockets. New bone volume (bone volume fraction; BV/TV) and Trabecular Separation (Tb.Sp) were used as the parameters for extraction socket healing.
Results: Micro CT analysis for alveolar bone revealed that BV/TV in ZA/LP-medicated group was significantly lower compared with saline, ZA or LP single administration group. In addition, the value of Tb.Sp in ZA/LP-medicated group was significantly higher compared with other groups.
Conclusions: Our results suggested long-term administration of PPI may delay healing of extraction sockets in patients with Bisphosphonate treatment.