Abstract
Objective The present study aimed to investigate the role of periapical diseases in inducing medication-related osteonecrosis of the jaws (MRONJ) using an ovariectomized (OVX) mice model. Materials and Methods Twenty C57BL/6N female mice were randomly assigned to two groups. All mice were subjected to bilateral ovariectomy and then treated with oncologic dose of zoledronic acid (ZA) or vehicle for twelve weeks. Eight weeks after commence of drug administration, a pulpal exposure (PE) operation was performed on the first right lower molar to induce periapical periodontitis; the contralateral non-PE tooth was used as control. All animals were sacrificed four weeks after pulpal exposure, and the mandibles were harvested for radiological and histomorphometrical analysis. Results Micro computed tomography (μ-CT) examination demonstrated that periapical diseases significantly increased alveolar bone resorption, and the resorption was greatly attenuated by ZA treatment. Concurrent ZA therapy significantly increased bone density and histological osteocyte necrosis in the presence of periapical lesions. Conclusion ZA treatment reduced bone absorption resulting from periapical disease but increased the risk of developing MRONJ in the ovariectomized mouse model.
Highlights
Medication-related osteonecrosis of the jaws (MRONJ) is a critical clinical problem which is characterized by the progressive destruction and death of bone tissue of the jaws as a consequence of antiresorptive drug administration
Rodents do not normally show coupled remodeling in the cortical bone. This characteristic poses a limitation as an experimental model for MRONJ, as the pathogenesis is thought to be associated with aberrant intracortical remodeling [13, 14]
There was no significant interaction between the action of zoledronic acid (ZA) and periapical diseases on osteonecrosis, our results showed that periapical infection coupled with nitrogen-containing bisphosphonate (N-Bps) administration increased the number of nonviable osteocytes
Summary
The present study aimed to investigate the role of periapical diseases in inducing medication-related osteonecrosis of the jaws (MRONJ) using an ovariectomized (OVX) mice model. All mice were subjected to bilateral ovariectomy and treated with oncologic dose of zoledronic acid (ZA) or vehicle for twelve weeks. Eight weeks after commence of drug administration, a pulpal exposure (PE) operation was performed on the first right lower molar to induce periapical periodontitis; the contralateral non-PE tooth was used as control. Micro computed tomography (μ-CT) examination demonstrated that periapical diseases significantly increased alveolar bone resorption, and the resorption was greatly attenuated by ZA treatment. Concurrent ZA therapy significantly increased bone density and histological osteocyte necrosis in the presence of periapical lesions. ZA treatment reduced bone absorption resulting from periapical disease but increased the risk of developing MRONJ in the ovariectomized mouse model
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