Role of microcracks in the pathogenesis of bisphosphonate-related osteonecrosis of the jaw

Jin Woo Kim, Maria Erika A. Landayan, Ju Young Lee, Jacquiline Czar I. Tatad, Sun Jong Kim, Myung Rae Kim, Inho Cha

Research output: Contribution to journalArticle

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Abstract

Objectives: The aim of this study was to investigate the potential role of microcrack accumulation in the pathogenesis of bisphosphonate-related osteonecrosis of the jaw (ONJ) through an animal model. Materials and methods: Twenty-four ovariectomized rats were randomly divided into a bisphosphonate group (n = 19) and control group (n = 5) and weekly injected with zoledronic acid and normal saline, respectively. After 6 weeks, surgical intervention was performed, and the injections were continued for eight additional weeks. Then, the animals were sacrificed, and ONJ lesions were inspected for the presence of microcracks using scanning electron microscopy. Measurements included bone dimension, number of cracks, crack length, and normalized indices; crack density (Cr.Dn) and crack surface density (Cr.S.Dn) were used for group comparison. Results: Both number of cracks and crack length in the bisphosphonate group were greater than those in the control group (P < 0.05). Of the 19 rats injected with bisphosphonates, 13 rats (68.4 %) were classified into the ONJ group. Cr.Dn and Cr.S.Dn were significantly greater in the ONJ group than in the non-ONJ group, indicating accumulation of unrepaired microcracks (P < 0.05). Seventy-two percent of microcracks in the ONJ group conformed to the defined length that was considered significant according to a previous literature (30–80 μm); whereas 12 % of microcracks in the non-ONJ group were considered significant (P < 0.05). Conclusion: Accumulation of unrepaired microcracks was significantly associated with the development of bisphosphonate-related ONJ. Further research is required to determine the role of microcracks in the pathogenesis of bisphosphonate-related ONJ. Clinical Relevance: Long-term bisphosphonates use may deteriorate the biomechanical and physiological bone integrity, contributing to the pathogenesis of bisphosphonate-related ONJ.

Original languageEnglish
Pages (from-to)2251-2258
Number of pages8
JournalClinical Oral Investigations
Volume20
Issue number8
DOIs
Publication statusPublished - 2016 Nov 1

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Bisphosphonate-Associated Osteonecrosis of the Jaw
Jaw
Osteonecrosis
Diphosphonates
zoledronic acid
Bone and Bones
Control Groups
Electron Scanning Microscopy
Animal Models
Injections
Research

All Science Journal Classification (ASJC) codes

  • Dentistry(all)

Cite this

Kim, J. W., Landayan, M. E. A., Lee, J. Y., Tatad, J. C. I., Kim, S. J., Kim, M. R., & Cha, I. (2016). Role of microcracks in the pathogenesis of bisphosphonate-related osteonecrosis of the jaw. Clinical Oral Investigations, 20(8), 2251-2258. https://doi.org/10.1007/s00784-016-1718-2
Kim, Jin Woo ; Landayan, Maria Erika A. ; Lee, Ju Young ; Tatad, Jacquiline Czar I. ; Kim, Sun Jong ; Kim, Myung Rae ; Cha, Inho. / Role of microcracks in the pathogenesis of bisphosphonate-related osteonecrosis of the jaw. In: Clinical Oral Investigations. 2016 ; Vol. 20, No. 8. pp. 2251-2258.
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abstract = "Objectives: The aim of this study was to investigate the potential role of microcrack accumulation in the pathogenesis of bisphosphonate-related osteonecrosis of the jaw (ONJ) through an animal model. Materials and methods: Twenty-four ovariectomized rats were randomly divided into a bisphosphonate group (n = 19) and control group (n = 5) and weekly injected with zoledronic acid and normal saline, respectively. After 6 weeks, surgical intervention was performed, and the injections were continued for eight additional weeks. Then, the animals were sacrificed, and ONJ lesions were inspected for the presence of microcracks using scanning electron microscopy. Measurements included bone dimension, number of cracks, crack length, and normalized indices; crack density (Cr.Dn) and crack surface density (Cr.S.Dn) were used for group comparison. Results: Both number of cracks and crack length in the bisphosphonate group were greater than those in the control group (P < 0.05). Of the 19 rats injected with bisphosphonates, 13 rats (68.4 {\%}) were classified into the ONJ group. Cr.Dn and Cr.S.Dn were significantly greater in the ONJ group than in the non-ONJ group, indicating accumulation of unrepaired microcracks (P < 0.05). Seventy-two percent of microcracks in the ONJ group conformed to the defined length that was considered significant according to a previous literature (30–80 μm); whereas 12 {\%} of microcracks in the non-ONJ group were considered significant (P < 0.05). Conclusion: Accumulation of unrepaired microcracks was significantly associated with the development of bisphosphonate-related ONJ. Further research is required to determine the role of microcracks in the pathogenesis of bisphosphonate-related ONJ. Clinical Relevance: Long-term bisphosphonates use may deteriorate the biomechanical and physiological bone integrity, contributing to the pathogenesis of bisphosphonate-related ONJ.",
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Role of microcracks in the pathogenesis of bisphosphonate-related osteonecrosis of the jaw. / Kim, Jin Woo; Landayan, Maria Erika A.; Lee, Ju Young; Tatad, Jacquiline Czar I.; Kim, Sun Jong; Kim, Myung Rae; Cha, Inho.

In: Clinical Oral Investigations, Vol. 20, No. 8, 01.11.2016, p. 2251-2258.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Role of microcracks in the pathogenesis of bisphosphonate-related osteonecrosis of the jaw

AU - Kim, Jin Woo

AU - Landayan, Maria Erika A.

AU - Lee, Ju Young

AU - Tatad, Jacquiline Czar I.

AU - Kim, Sun Jong

AU - Kim, Myung Rae

AU - Cha, Inho

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N2 - Objectives: The aim of this study was to investigate the potential role of microcrack accumulation in the pathogenesis of bisphosphonate-related osteonecrosis of the jaw (ONJ) through an animal model. Materials and methods: Twenty-four ovariectomized rats were randomly divided into a bisphosphonate group (n = 19) and control group (n = 5) and weekly injected with zoledronic acid and normal saline, respectively. After 6 weeks, surgical intervention was performed, and the injections were continued for eight additional weeks. Then, the animals were sacrificed, and ONJ lesions were inspected for the presence of microcracks using scanning electron microscopy. Measurements included bone dimension, number of cracks, crack length, and normalized indices; crack density (Cr.Dn) and crack surface density (Cr.S.Dn) were used for group comparison. Results: Both number of cracks and crack length in the bisphosphonate group were greater than those in the control group (P < 0.05). Of the 19 rats injected with bisphosphonates, 13 rats (68.4 %) were classified into the ONJ group. Cr.Dn and Cr.S.Dn were significantly greater in the ONJ group than in the non-ONJ group, indicating accumulation of unrepaired microcracks (P < 0.05). Seventy-two percent of microcracks in the ONJ group conformed to the defined length that was considered significant according to a previous literature (30–80 μm); whereas 12 % of microcracks in the non-ONJ group were considered significant (P < 0.05). Conclusion: Accumulation of unrepaired microcracks was significantly associated with the development of bisphosphonate-related ONJ. Further research is required to determine the role of microcracks in the pathogenesis of bisphosphonate-related ONJ. Clinical Relevance: Long-term bisphosphonates use may deteriorate the biomechanical and physiological bone integrity, contributing to the pathogenesis of bisphosphonate-related ONJ.

AB - Objectives: The aim of this study was to investigate the potential role of microcrack accumulation in the pathogenesis of bisphosphonate-related osteonecrosis of the jaw (ONJ) through an animal model. Materials and methods: Twenty-four ovariectomized rats were randomly divided into a bisphosphonate group (n = 19) and control group (n = 5) and weekly injected with zoledronic acid and normal saline, respectively. After 6 weeks, surgical intervention was performed, and the injections were continued for eight additional weeks. Then, the animals were sacrificed, and ONJ lesions were inspected for the presence of microcracks using scanning electron microscopy. Measurements included bone dimension, number of cracks, crack length, and normalized indices; crack density (Cr.Dn) and crack surface density (Cr.S.Dn) were used for group comparison. Results: Both number of cracks and crack length in the bisphosphonate group were greater than those in the control group (P < 0.05). Of the 19 rats injected with bisphosphonates, 13 rats (68.4 %) were classified into the ONJ group. Cr.Dn and Cr.S.Dn were significantly greater in the ONJ group than in the non-ONJ group, indicating accumulation of unrepaired microcracks (P < 0.05). Seventy-two percent of microcracks in the ONJ group conformed to the defined length that was considered significant according to a previous literature (30–80 μm); whereas 12 % of microcracks in the non-ONJ group were considered significant (P < 0.05). Conclusion: Accumulation of unrepaired microcracks was significantly associated with the development of bisphosphonate-related ONJ. Further research is required to determine the role of microcracks in the pathogenesis of bisphosphonate-related ONJ. Clinical Relevance: Long-term bisphosphonates use may deteriorate the biomechanical and physiological bone integrity, contributing to the pathogenesis of bisphosphonate-related ONJ.

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