Rodents as an animal model for studying tooth extraction-related medication-related osteonecrosis of the jaw: assessment of outcomes

Henrique Hadad; Henrique R Matheus; Sara I Pai; Francisley A Souza; Fernando P S Guastaldi

doi:10.1016/j.archoralbio.2023.105875

Rodents as an animal model for studying tooth extraction-related medication-related osteonecrosis of the jaw: assessment of outcomes

Arch Oral Biol. 2024 Mar:159:105875. doi: 10.1016/j.archoralbio.2023.105875. Epub 2023 Dec 26.

Authors

Henrique Hadad¹, Henrique R Matheus², Sara I Pai³, Francisley A Souza⁴, Fernando P S Guastaldi⁵

Affiliations

¹ Department of Oral and Maxillofacial Surgery, Massachusetts General Hospital, Harvard School of Dental Medicine, Boston, MA, USA; Department of Diagnosis and Surgery, Oral & Maxillofacial Surgery Division, São Paulo State University (UNESP), School of Dentistry, Araçatuba, SP, Brazil.
² Department of Oral and Maxillofacial Surgery, Massachusetts General Hospital, Harvard School of Dental Medicine, Boston, MA, USA; Department of Diagnosis and Surgery, Periodontics Division, São Paulo State University (UNESP), School of Dentistry, Araçatuba, SP, Brazil.
³ Department of Surgery, Division of Otolaryngology-Head and Neck Surgery, Yale University School of Medicine, New Haven, CT, USA.
⁴ Department of Diagnosis and Surgery, Oral & Maxillofacial Surgery Division, São Paulo State University (UNESP), School of Dentistry, Araçatuba, SP, Brazil.
⁵ Department of Oral and Maxillofacial Surgery, Massachusetts General Hospital, Harvard School of Dental Medicine, Boston, MA, USA. Electronic address: fguastaldi@mgh.harvard.edu.

PMID: 38160519
DOI: 10.1016/j.archoralbio.2023.105875

Abstract

Objective: To assess the outcomes of several rodent animal models for studying tooth extraction-related medication-related osteonecrosis of the jaw (MRONJ).

Design: After a search of the databases, 2004 articles were located, and 118 corroborated the inclusion factors (in vivo studies in rodents evaluating tooth extraction as a risk factor for the development of MRONJ).

Results: Numerous studies attempting to establish an optimal protocol to induce MRONJ were found. Zoledronic acid (ZA) was the most used drug, followed by alendronate (ALN). Even when ZA did not lead to the development of MRONJ, its effect compromised the homeostasis of the bone and soft tissue. The association of other risk factors (dexamethasone, diabetes, and tooth-related inflammatory dental disease) besides tooth extraction also played a role in the development of MRONJ. In addition, studies demonstrated a relationship between cumulative dose and MRONJ.

Conclusions: Both ZA and ALN can lead to MRONJ in rodents when equivalent human doses (in osteoporosis or cancer treatment) are used. Local oral risk factors and tooth-related inflammatory dental disease increase the incidence of MRONJ in a tooth extraction-related rodent model.

Keywords: Antiresorptive; BRONJ; Bisphosphonates; MRONJ, ONJ.

Publication types

Review

MeSH terms

Alendronate / adverse effects
Animals
Bisphosphonate-Associated Osteonecrosis of the Jaw* / etiology
Bone Density Conservation Agents* / adverse effects
Diphosphonates / adverse effects
Humans
Models, Animal
Rodentia
Tooth Extraction / adverse effects
Zoledronic Acid / adverse effects

Substances

Diphosphonates
Bone Density Conservation Agents
Zoledronic Acid
Alendronate