Animal model for medication-related osteonecrosis of the jaw with precedent metabolic bone disease

Jin Woo Kim; Jacquiline Czar I. Tatad; Maria Erika A. Landayan; Sun Jong Kim; Myung Rae Kim

doi:10.1016/j.bone.2015.08.012

Animal model for medication-related osteonecrosis of the jaw with precedent metabolic bone disease

Jin Woo Kim, Jacquiline Czar I. Tatad, Maria Erika A. Landayan, Sun Jong Kim, Myung Rae Kim

Department of Dentistry

Research output: Contribution to journal › Article › peer-review

29 Scopus citations

Abstract

Despite the fact that the medications used to treat abnormal bone conditions often induce osteonecrosis of the jaw (ONJ), previous attempts to establish an animal model for ONJ have shown insufficient consideration for this important prerequisite for the development of the disease. The purpose of this study was to establish an animal model with the most common metabolic bone disease, osteoporosis. Ninty-six rats were randomly divided into ovariectomy (Ov) group (n. = 48) and sham-operated group (n. = 48). Six weeks after Ov or sham surgery, rats in each group were subdivided into bisphosphonate group (n. = 36 each) and control group (n. = 12 each) and injected with zoledronic acid and normal saline, respectively, once a week. After additional 6. weeks, surgical intervention was performed, and the injections were continued for 8 more weeks. The animals were then sacrificed for further macroscopic, histological, histomorphometric, radiological, and bone biomarker investigations. As histologically determined, the Ov group (77.8%) showed higher ONJ prevalence compared to the sham group (47.2%; P<. 0.05). Micro-structural and histomorphometric assessments revealed that rats with ONJ (ONJ group) presented with deteriorated bone architectures with higher necrotic bone fraction and lower number of osteoclasts (P<. 0.05). Compared to the sham-operated ONJ group, the Ov ONJ group showed significantly lower values of Tb.N, Tb.Sp, Conn.D, N.Oc/T.Ar, and TRACP 5b and CTX/TRACP (P<. 0.05).The ovariectomized rat model in this study successfully mimicked human ONJ lesions with an underlying bone disease and showed different bone characteristics than that of the previous ONJ model. Based on the differences, further researches for investigating pathophysiology of ONJ, including various pharmacological responses for deteriorated bone environment, are required.

Original language	English
Pages (from-to)	442-448
Number of pages	7
Journal	Bone
Volume	81
DOIs	https://doi.org/10.1016/j.bone.2015.08.012
State	Published - 1 Dec 2015

Bibliographical note

Funding Information:
This study was supported by the Ewha Global Top5 Grant ( 1-2013-0469-001-1 ), Ewha Womans University, Seoul, Korea. The authors declare no potential conflicts of interest with respect to the authorship and/or publication of this article.

Publisher Copyright:
© 2015 Elsevier Inc.

Keywords

Animal model
Bisphosphonates
Medication-related osteonecrosis of the jaw
Osteoporosis
Ovariectomy

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.bone.2015.08.012

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title = "Animal model for medication-related osteonecrosis of the jaw with precedent metabolic bone disease",

abstract = "Despite the fact that the medications used to treat abnormal bone conditions often induce osteonecrosis of the jaw (ONJ), previous attempts to establish an animal model for ONJ have shown insufficient consideration for this important prerequisite for the development of the disease. The purpose of this study was to establish an animal model with the most common metabolic bone disease, osteoporosis. Ninty-six rats were randomly divided into ovariectomy (Ov) group (n. = 48) and sham-operated group (n. = 48). Six weeks after Ov or sham surgery, rats in each group were subdivided into bisphosphonate group (n. = 36 each) and control group (n. = 12 each) and injected with zoledronic acid and normal saline, respectively, once a week. After additional 6. weeks, surgical intervention was performed, and the injections were continued for 8 more weeks. The animals were then sacrificed for further macroscopic, histological, histomorphometric, radiological, and bone biomarker investigations. As histologically determined, the Ov group (77.8%) showed higher ONJ prevalence compared to the sham group (47.2%; P<. 0.05). Micro-structural and histomorphometric assessments revealed that rats with ONJ (ONJ group) presented with deteriorated bone architectures with higher necrotic bone fraction and lower number of osteoclasts (P<. 0.05). Compared to the sham-operated ONJ group, the Ov ONJ group showed significantly lower values of Tb.N, Tb.Sp, Conn.D, N.Oc/T.Ar, and TRACP 5b and CTX/TRACP (P<. 0.05).The ovariectomized rat model in this study successfully mimicked human ONJ lesions with an underlying bone disease and showed different bone characteristics than that of the previous ONJ model. Based on the differences, further researches for investigating pathophysiology of ONJ, including various pharmacological responses for deteriorated bone environment, are required.",

keywords = "Animal model, Bisphosphonates, Medication-related osteonecrosis of the jaw, Osteoporosis, Ovariectomy",

author = "Kim, {Jin Woo} and Tatad, {Jacquiline Czar I.} and Landayan, {Maria Erika A.} and Kim, {Sun Jong} and Kim, {Myung Rae}",

note = "Funding Information: This study was supported by the Ewha Global Top5 Grant ( 1-2013-0469-001-1 ), Ewha Womans University, Seoul, Korea. The authors declare no potential conflicts of interest with respect to the authorship and/or publication of this article. Publisher Copyright: {\textcopyright} 2015 Elsevier Inc.",

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AU - Tatad, Jacquiline Czar I.

AU - Landayan, Maria Erika A.

AU - Kim, Sun Jong

AU - Kim, Myung Rae

N1 - Funding Information: This study was supported by the Ewha Global Top5 Grant ( 1-2013-0469-001-1 ), Ewha Womans University, Seoul, Korea. The authors declare no potential conflicts of interest with respect to the authorship and/or publication of this article. Publisher Copyright: © 2015 Elsevier Inc.

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N2 - Despite the fact that the medications used to treat abnormal bone conditions often induce osteonecrosis of the jaw (ONJ), previous attempts to establish an animal model for ONJ have shown insufficient consideration for this important prerequisite for the development of the disease. The purpose of this study was to establish an animal model with the most common metabolic bone disease, osteoporosis. Ninty-six rats were randomly divided into ovariectomy (Ov) group (n. = 48) and sham-operated group (n. = 48). Six weeks after Ov or sham surgery, rats in each group were subdivided into bisphosphonate group (n. = 36 each) and control group (n. = 12 each) and injected with zoledronic acid and normal saline, respectively, once a week. After additional 6. weeks, surgical intervention was performed, and the injections were continued for 8 more weeks. The animals were then sacrificed for further macroscopic, histological, histomorphometric, radiological, and bone biomarker investigations. As histologically determined, the Ov group (77.8%) showed higher ONJ prevalence compared to the sham group (47.2%; P<. 0.05). Micro-structural and histomorphometric assessments revealed that rats with ONJ (ONJ group) presented with deteriorated bone architectures with higher necrotic bone fraction and lower number of osteoclasts (P<. 0.05). Compared to the sham-operated ONJ group, the Ov ONJ group showed significantly lower values of Tb.N, Tb.Sp, Conn.D, N.Oc/T.Ar, and TRACP 5b and CTX/TRACP (P<. 0.05).The ovariectomized rat model in this study successfully mimicked human ONJ lesions with an underlying bone disease and showed different bone characteristics than that of the previous ONJ model. Based on the differences, further researches for investigating pathophysiology of ONJ, including various pharmacological responses for deteriorated bone environment, are required.

AB - Despite the fact that the medications used to treat abnormal bone conditions often induce osteonecrosis of the jaw (ONJ), previous attempts to establish an animal model for ONJ have shown insufficient consideration for this important prerequisite for the development of the disease. The purpose of this study was to establish an animal model with the most common metabolic bone disease, osteoporosis. Ninty-six rats were randomly divided into ovariectomy (Ov) group (n. = 48) and sham-operated group (n. = 48). Six weeks after Ov or sham surgery, rats in each group were subdivided into bisphosphonate group (n. = 36 each) and control group (n. = 12 each) and injected with zoledronic acid and normal saline, respectively, once a week. After additional 6. weeks, surgical intervention was performed, and the injections were continued for 8 more weeks. The animals were then sacrificed for further macroscopic, histological, histomorphometric, radiological, and bone biomarker investigations. As histologically determined, the Ov group (77.8%) showed higher ONJ prevalence compared to the sham group (47.2%; P<. 0.05). Micro-structural and histomorphometric assessments revealed that rats with ONJ (ONJ group) presented with deteriorated bone architectures with higher necrotic bone fraction and lower number of osteoclasts (P<. 0.05). Compared to the sham-operated ONJ group, the Ov ONJ group showed significantly lower values of Tb.N, Tb.Sp, Conn.D, N.Oc/T.Ar, and TRACP 5b and CTX/TRACP (P<. 0.05).The ovariectomized rat model in this study successfully mimicked human ONJ lesions with an underlying bone disease and showed different bone characteristics than that of the previous ONJ model. Based on the differences, further researches for investigating pathophysiology of ONJ, including various pharmacological responses for deteriorated bone environment, are required.

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Animal model for medication-related osteonecrosis of the jaw with precedent metabolic bone disease

Abstract

Bibliographical note

Keywords

UN SDGs

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