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, In Ho
N1 - Publisher Copyright:
© 2016, Springer-Verlag Berlin Heidelberg.
PY - 2016/11/1
Y1 - 2016/11/1
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.
KW - Bisphosphonate-related osteonecrosis of the jaw
KW - Bisphosphonates
KW - Microarchitecture
KW - Microcrack
KW - Rat
UR - http://www.scopus.com/inward/record.url?scp=84955300187&partnerID=8YFLogxK
U2 - 10.1007/s00784-016-1718-2
DO - 10.1007/s00784-016-1718-2
M3 - Article
C2 - 26795624
AN - SCOPUS:84955300187
SN - 1432-6981
VL - 20
SP - 2251
EP - 2258
JO - Clinical Oral Investigations
JF - Clinical Oral Investigations
IS - 8
ER -