The effects of different doses of teriparatide on bisphosphonate-related osteonecrosis of the jaw in mice.

OBJECTIVES

This study aimed to investigate the therapeutic effect of different doses of teriparatide (TPTD) on bisphosphonate-related osteonecrosis of the jaw (BRONJ).

MATERIALS AND METHODS

To establish the BRONJ model, 20 mice were randomly divided into two groups: a group that received tail vein administration of zoledronic acid with dexamethasone (ZA-125 µg/kg, DEX 5 mg/kg) and a group that received saline weekly. The mice subsequently underwent bilateral maxillary first molar extraction. After 8 weeks of modelling administration, the maxilla samples were examined by micro-computed tomography and histological staining (haematoxylin and eosin, Masson's trichrome and tartrate-resistant acid phosphatase) and the cytokine level was measured (enzyme-linked immunosorbent assay and Western blot). To determine the role of TPTD in BRONJ, the same protocol as previously described was applied in 100 mice (80 received ZA + DEX, and 20 received saline). After 8 weeks of modelling administration, 80 ZA + DEX mice were randomly divided into four groups: three groups with subcutaneous administration of TPTD (i.e. T1-3, T2-10 and T3-30 µg kg  day ) and one group with saline daily for the next 8 weeks. The other 20 saline mice continued to receive saline daily.

RESULTS

In Part 1, the level of receptor activator of nuclear factor-kappa Β ligand and the numbers of osteoclasts differed between the model and control groups. In Part 2, we found that TPTD had a positive effect on BRONJ in a mouse model based on clinical and histomorphological observations. Among the three treatment groups, the T1 and T2 groups significantly differed from the model group, whereas the T3 group showed no statistical differences.

CONCLUSION

Subcutaneous administration of TPTD has a beneficial effect on BRONJ in mice. Nevertheless, further studies are needed to determine whether the therapeutic effect on BRONJ is dose-dependent.