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

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. 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. 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 mu m); whereas 12 % of microcracks in the non-ONJ group were considered significant (P < 0.05). 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. Long-term bisphosphonates use may deteriorate the biomechanical and physiological bone integrity, contributing to the pathogenesis of bisphosphonate-related ONJ.