Division of Diagnostic and Surgical Sciences, UCLA School of Dentistry, Los Angeles, CA, USA.
UCLA Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
J Dent Res. 2021 Jul;100(7):746-753. doi: 10.1177/0022034520986804. Epub 2021 Jan 21.
Osteonecrosis of the jaws (ONJ), a severe side effect of antiresorptive medications, is characterized by exposed, nonhealing bone in the oral cavity. Treatment options for ONJ range from management of symptomology to surgical resection of the affected area. Antiresorptive discontinuation, often termed a "drug holiday," has been used for managing ONJ patients. Antiresorptives can be discontinued prior to oral surgical procedures, such as tooth extraction, to prevent ONJ development or in patients with established ONJ to accelerate healing. Here, our objective was to test these clinical scenarios using the potent bisphosphonate, zoledronic acid (ZA), and the denosumab surrogate for rodents, OPG-Fc, in a rat model of ONJ. Animals were pretreated with antiresorptives or saline, after which we induced ONJ using periapical disease and tooth extraction. In our first experimental design, antiresorptives were discontinued 1 wk prior to tooth extraction, and animals were evaluated 4 wk later for clinical, radiographic, and histologic features of ONJ. In the second experiment, ONJ was established and antiresorptives were discontinued for 4 wk. Discontinuation of OPG-Fc, but not ZA, prior to tooth extraction ameliorated subsequent ONJ development. In contrast, discontinuation of either ZA or OPG-Fc in rats with established ONJ did not lead to ONJ resolution. In conclusion, our findings suggest that antiresorptive discontinuation is dependent on both the type of antiresorptive and the timing of discontinuation.
颌骨坏死（ONJ）是一种抗吸收药物的严重副作用，其特征是口腔中暴露的、无法愈合的骨骼。ONJ 的治疗选择范围从症状管理到受影响区域的手术切除。抗吸收药物的停药，通常称为“药物假期”，已被用于管理 ONJ 患者。在进行口腔手术（如拔牙）之前，可以停止使用抗吸收药物，以防止 ONJ 发展，或者在已经患有 ONJ 的患者中使用，以加速愈合。在这里，我们的目的是使用强效双膦酸盐唑来膦酸（ZA）和啮齿动物的 denosumab 替代品 OPG-Fc，在 ONJ 大鼠模型中测试这些临床情况。动物先用抗吸收药物或生理盐水预处理，然后用根尖病和拔牙来诱导 ONJ。在我们的第一个实验设计中，在拔牙前 1 周停止使用抗吸收药物，然后在 4 周后评估动物的 ONJ 临床、放射学和组织学特征。在第二个实验中，建立了 ONJ，并停止使用抗吸收药物 4 周。在拔牙前停止使用 OPG-Fc，但不是 ZA，可以改善随后的 ONJ 发展。相比之下，在已经患有 ONJ 的大鼠中停止使用 ZA 或 OPG-Fc 并不导致 ONJ 缓解。总之，我们的发现表明，抗吸收药物的停药取决于抗吸收药物的类型和停药的时间。
