Departmental Papers (Dental)
Document Type
Journal Article
Date of this Version
7-2010
Publication Source
American Journal of Pathology
Volume
177
Issue
1
Start Page
280
Last Page
290
DOI
10.2353/ajpath.2010.090592
Abstract
Bisphosphonate-associated osteonecrosis of the jaw (BONJ) is a morbid bone disease linked to long-term bisphosphonate use. Despite its broad health impact, mechanistic study is lacking. In this study, we have established a mouse model of BONJ-like disease based on the equivalent clinical regimen in myeloma patients, a group associated with high risk of BONJ. We demonstrate that the murine BONJ-like disease recapitulates major clinical and radiographical manifestations of the human disease, including characteristic features of osseous sclerosis, sequestra, avascular, and radiopaque alveolar bone in the jaw that persists beyond a normal course of wound healing following tooth extraction. We find that long-term administration of bisphosphonates results in an increase in the size and number of osteoclasts and the formation of giant osteoclast-like cells within the alveolar bone. We show that the development of necrotic bone and impaired soft tissue healing in our mouse model is dependent on long-term use of high-dose bisphosphonates, immunosuppressive and chemotherapy drugs, as well as mechanical trauma. Most importantly, we demonstrate that bisphosphonate is the major cause of BONJ-like disease in mice, mediated in part by its ability to suppress osseous angiogenesis and bone remodeling. The availability of this novel mouse model of BONJ-like disease will help elucidate the pathophysiology of BONJ and ultimately develop novel approaches for prevention and treatment of human BONJ. Copyright © American Society for Investigative Pathology.
Keywords
EMTREE drug terms: bisphosphonic acid derivative, dexamethasone, docetaxel, zoledronic acid EMTREE medical terms: alveolar bone, angiogenesis, animal experiment, animal tissue, article, bone necrosis, bone remodeling, healing impairment, jaw osteonecrosis, jaw radiography, mouse, myeloma, nonhuman, osteoclast, osteosclerosis, priority journal, tooth extraction, wound healing
Recommended Citation
Bi, Y., Gao, Y., Ehirchiou, D., Cao, C., Kikuiri, T., Le, A., Shi, S., & Zhang, L. (2010). Bisphosphonates Cause Osteonecrosis of the Jaw-Like Disease in Mice. American Journal of Pathology, 177 (1), 280-290. http://dx.doi.org/10.2353/ajpath.2010.090592
Date Posted: 10 February 2023
This document has been peer reviewed.
Comments
At the time of publication, author Anh Le was affiliated with the University of Southern California, School of Dentistry. Currently, (s)he is a faculty member at the School of Dental Medicine at the University of Pennsylvania.
At the time of publication, author Songtao Shi was affiliated with the University of Southern California, School of Dentistry. Currently, (s)he is a faculty member at the School of Dental Medicine at the University of Pennsylvania.