Browsing by Subject "Osteonecrosis of the jaw"

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    Absence of exposed bone following dental extraction in beagle dogs treated with nine-months of high dose zoledronic acid combined with dexamethasone
    (Elsevier, 2013) Allen, Matthew R.; Chu, Tien-Min Gabriel; Ruggiero, Salvatore L.; Anatomy, Cell Biology and Physiology, School of Medicine
    Purpose: Factors contributing to osteonecrosis of the jaw with anti-remodeling drug treatment are unclear. Epidemiologic and experimental studies have suggested the combination of bisphosphonates and dexamethasone results in osteonecrosis of the jaw more often than either agent alone. The goal of this study was to assess the combination of these 2 drugs in a large animal model previously shown to be susceptible to exposed bone in the oral cavity when treated with bisphosphonates. Materials and methods: Skeletally mature beagle dogs were untreated controls or treated with zoledronic acid (ZOL), dexamethasone (DEX), or ZOL plus DEX. ZOL and DEX were given at doses based on those used in humans. All animals underwent single molar extraction at 7 and 8 months after the start of the study. Extraction sites were obtained at month 9 for assessment of osseous healing using micro-computed tomography and histology. Results: No animals were observed to have exposed bone after dental extraction, yet 1 animal treated with ZOL and 1 treated with ZOL plus DEX had severely disrupted extraction sites as viewed by computed tomography and histology. These 2 animals had an intense periosteal reaction that was less obvious but still present in all ZOL-treated animals and absent from untreated animals. There was no significant difference in bone volume within the socket among groups at 4 or 8 weeks after healing, yet the ratio of surface to volume was significantly higher in animals treated with ZOL plus DEX at 8 weeks compared with control animals. Conclusions: These findings suggest a more complex pathophysiology to osteonecrosis of the jaw than is implied by previous epidemiologic studies and those in rodents and raise questions about the potential role of DEX in its etiology.
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    The pathogenesis of bisphosphonate-related osteonecrosis of the jaw: so many hypotheses, so few data.
    (2009-05) Allen, Matthew R.; Burr, David B.
    Bisphosphonate-related osteonecrosis of the jaw (BRONJ) has generated great interest in the medical and research communities yet remains an enigma, given its unknown pathogenesis. The goal of this review is to summarize the various proposed hypotheses underlying BRONJ. Although a role of the oral mucosa has been proposed, the bone is likely the primary tissue of interest for BRONJ. The most popular BRONJ hypothesis-manifestation of necrotic bone resulting from bisphosphonate--induced remodeling suppression--is supported mostly by indirect evidence, although recent data have shown that bisphosphonates significantly reduce remodeling in the jaw. Remodeling suppression would be expected, and has been shown, to allow accumulation of nonviable osteocytes, whereas a more direct cytotoxic effect of bisphosphonates on osteocytes has also been proposed. Bisphosphonates have antiangiogenic effects, leading to speculation that this could contribute to the BRONJ pathogenesis. Compromised angiogenesis would most likely be involved in post-intervention healing, although other aspects of the vasculature (eg, blood flow) could contribute to BRONJ. Despite infection being present in many BRONJ patients, there is no clear evidence as to whether infection is a primary or secondary event in the pathophysiology. In addition to these main factors proposed in the pathogenesis, numerous cofactors associated with BRONJ (eg, diabetes, smoking, dental extraction, concurrent medications) could interact with bisphosphonates and affect remodeling, angiogenesis/blood flow, and/or infection. Because our lack of knowledge concerning BRONJ pathogenesis results from a lack of data, it is only through the initiation of hypothesis-driven studies that significant progress will be made to understand this serious and debilitating condition.