Absence of exposed bone following dental extraction in beagle dogs treated with nine-months of high dose zoledronic acid combined with dexamethasone

摘要

The factors contributing to osteonecrosis of the jaw (ONJ) with anti-remodeling drug treatment are unclear. Both epidemiological and experimental studies have suggested the combination of bisphosphonates and dexamethasone results in ONJ more often than either agent alone. The goal of this study was to assess the combination of these two drugs in a large animal model previously shown to be susceptible to exposed bone in the oral cavity when treated with bisphosphonates. Skeletally mature beagle dogs were either untreated controls, or treated with zoledronic acid (ZOL), dexamethasone (DEX), or ZOL + DEX. Both zoledronic acid and dexamethasone were given at doses based on those used in humans. All animals underwent single molar extraction at both 7 and 8 months following the start of the study. Extraction sites were obtained at month 9 for assessment of osseous healing using micro-computed tomography and histology. No animals were observed to have exposed bone following dental extraction yet one animal treated with ZOL and one with ZOL+DEX had severely disrupted extraction sites as viewed by CT and histology. These two animals had intense periosteal reaction that was less obvious but still present on all ZOL-treated animals and absent from untreated animals. There was no significant difference in bone volume within the socket among groups at either 4 or 8 weeks post-healing yet the surface/volume ratio was significantly higher in animals treated with ZOL+DEX at 8 weeks compared to control animals. These findings suggest a more complex pathophysiology to ONJ than is implied by previous epidemiological studies as well as those in rodents and raise questions about the potential role of dexamethasone in its etiology.