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Review
. 2018 Oct;46(10):4277-4296.
doi: 10.1177/0300060518788987. Epub 2018 Aug 9.

Pathogenesis of Medication-Related Osteonecrosis of the Jaw: A Comparative Study of in Vivo and in Vitro Trials

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Free PMC article
Review

Pathogenesis of Medication-Related Osteonecrosis of the Jaw: A Comparative Study of in Vivo and in Vitro Trials

Henrik Holtmann et al. J Int Med Res. .
Free PMC article

Abstract

Objective This study was performed to determine whether the results of prevailing in vivo and in vitro studies offer a reliable model for investigation of medication-related osteonecrosis of the jaw (MRONJ). Methods Embase, Medline, and the Cochrane Library were searched for articles published from September 2003 to June 2017 involving experimental approaches to the pathogenesis of MRONJ. In vivo and in vitro trials were analyzed with respect to the scientific question, study design, methodology, and results. Results Of 139 studies, 87, 46, and 6 conducted in vivo, in vitro, and both in vivo and in vitro experiments, respectively. Rats, mice, dogs, minipigs, sheep, and rabbits were the preferred animal models used. Osteoblasts, osteoclasts, fibroblasts, keratinocytes, macrophages, and human umbilical vein endothelial cells were the preferred cell types. Zoledronate, alendronate, ibandronate, and risedronate were the most frequent bisphosphonates used. MRONJ was most reliably induced in minipigs because of the close relationship with human bone physiology. In vitro studies showed that reduced viability, growth, and migration of cells in the bone and soft tissues were causative for MRONJ. Other than exposed jawbone after tooth extraction, no reliable cofactors were found. Conclusion The minipig is the most suitable animal model for MRONJ.

Keywords: Osteonecrosis; in vitro; in vivo; jaw; medication-related; minipig.

Figures

Figure 1.
Figure 1.
Number of published in vivo studies on medication-related osteonecrosis of the jaw published from 2003 to 2017 assorted by the test animal species used.
Figure 2.
Figure 2.
Number of in vitro studies on medication-related osteonecrosis of the jaw published from 2003 to 2017 assorted by the cell type analyzed. HUVEC = human umbilical vein endothelial cells; FB = fibroblasts; KC = keratinocytes; MP = macrophages; OC = osteoclasts; OB = osteoblasts.
Figure 3.
Figure 3.
Number of combined in vivo/in vitro studies on medication-related osteonecrosis of the jaw published from 2003 to 2017 assorted by the test animal species used and cell type analyzed. Ca(OH)2 = hydroxyapatite; MP = macrophages; FB = fibroblasts; KC = keratinocytes; OC = osteoclasts.

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