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

  • Mohammad ZandiEmail author
  • Arash Dehghan
  • Payam Amini
  • Shideh Doulati
  • Leila Rezaeian
Original Article



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).


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.


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.


Teriparatide Mandibular fracture Osteonecrosis Healing Rat 



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


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

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

Informed consent

For this type of study, formal consent is not required.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Mohammad Zandi
    • 1
    • 2
    Email author
  • Arash Dehghan
    • 3
  • Payam Amini
    • 4
  • Shideh Doulati
    • 5
  • Leila Rezaeian
    • 5
  1. 1.Department of Oral and Maxillofacial Surgery, Faculty of DentistryHamadan University of Medical SciencesHamadanIran
  2. 2.Dental Research CenterHamadan University of Medical SciencesHamadanIran
  3. 3.Department of PathologyHamadan University of Medical SciencesHamadanIran
  4. 4.Department of Epidemiology and Reproductive Health, Reproductive Epidemiology Research Center, Royan Institute for Reproductive BiomedicineACECRTehranIran
  5. 5.Department of Oral and Maxillofacial SurgeryHamadan University of Medical SciencesHamadanIran

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