Evaluation of the effect of teriparatide therapy on mandibular fracture healing in rats with medication-related osteonecrosis of the jaw

Abstract

Objective

The aim of this study was to evaluate the effect of teriparatide therapy on mandibular fracture healing in rats with medication-related osteonecrosis of the jaw (MRONJ).

Materials and methods

To induce MRONJ, a total of 120 rats received intravenous zoledronate 0.06 mg/kg once a week for 6 weeks and their right mandibular first molar was extracted. Eighty of 94 rats with MRONJ were randomly selected and underwent unilateral mandibular osteotomy to replicate a fracture. After surgery, the rats were randomly assigned to T (teriparatide-treated) and C (control) groups. Group T (n = 40) received subcutaneous injection of 2 μg/kg/day teriparatide and group C (n = 40) received the same volume of normal saline until sacrifice. Four and 8 weeks after surgery, 20 rats in each group were sacrificed. Fracture healing was scored using a histological grading system (1 to 10).

Results

In group C, at 4 weeks and 8 weeks post-fracture, fibrous and cartilaginous tissues and scant bone formation at the fracture site and lacunae without osteocyte in adjacent mandibular bone were seen. In group T, substantial amounts of new trabecular bone rimmed by osteoblasts and some areas of remodeled mature bone were seen. After 8 weeks, extensive replacement of trabecular bone with mature bone occurred. Except between C4 and C8 groups, the healing score was significantly different between all subgroups.

Conclusion

Teriparatide therapy successfully improved mandibular fracture healing in rats with MRONJ. However, this study was limited by the use of an animal model whose anatomy, physiology, and drug metabolism might be different from humans.

Clinical relevance

The present study showed that teriparatide therapy may be used adjunctive to surgery in the treatment of mandibular fractures in MRONJ patients.

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Acknowledgements

This study has been adapted from a doctoral thesis at Hamadan University of Medical Sciences.

Funding

The study was funded by the vice-chancellor for Research and Technology, Hamadan University of Medical Sciences (no. 9507134134).

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Correspondence to Mohammad Zandi.

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Zandi, M., Dehghan, A., Amini, P. et al. Evaluation of the effect of teriparatide therapy on mandibular fracture healing in rats with medication-related osteonecrosis of the jaw. Clin Oral Invest 23, 3987–3993 (2019). https://doi.org/10.1007/s00784-019-02830-2

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Keywords

  • Teriparatide
  • Mandibular fracture
  • Osteonecrosis
  • Healing
  • Rat