Preventive effect of fluvastatin on the development of medication-related osteonecrosis of the jaw
Preventive effect of fluvastatin on the development of medication-related osteonecrosis of the jaw
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DOI：
10.1038/s41598-020-61724-6
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发表时间：
2020-03-27
影响因子：
4.6
通讯作者：
Koyano, Kiyoshi
中科院分区：
文献类型：
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作者：
Adachi, Naomi;Ayukawa, Yasunori;Koyano, Kiyoshi
药物相关性颌骨骨坏死（MRONJ）发生在接受口腔手术的患者中，同时接受双膦酸盐、地舒单抗或抗血管生成剂治疗。我们采用MRONJ样大鼠模型来研究在拔牙部位注射氟伐他汀是否可以预防MRONJ样病变。通过用唑来膦酸盐和地塞米松治疗大鼠，拔牙，并立即在拔牙部位注射氟伐他汀来创建MRONJ样模型。实验组分为低（0.1mg/kg; FS-L）、中（1.0mg/kg; FS-M）和高（10 mg/kg; FS-H）三个剂量组。FS-M（p=0.028）和FS-H（p=0.041）组的坏死骨暴露量显著低于MRONJ组。FS-M（p=0.042）和FS-H（p=0.041）组上皮表面边缘之间的距离显著缩短。FS-H组的坏死骨面积和坏死骨比率显著较小（分别为p=0.041和p=0.042）。FS-H组在mu-CT图像上计算的骨体积分数显著大于MRONJ组（p=0.021）。我们的研究结果表明，拔牙后单次局部注射氟伐他汀可以潜在地降低大鼠发生MRONJ样病变的机会。
Medication-related osteonecrosis of the jaw (MRONJ) occurs in patients undergoing oral surgery while medicated with bisphosphonate, denosumab or anti-angiogenic agents. We employed a MRONJ-like rat model to investigate whether injecting fluvastatin at extraction sites prevents MRONJ-like lesion. A MRONJ-like model was created by treating rats with zoledronate and dexamethasone, extracting teeth, and immediately injecting fluvastatin at the extraction site. The experimental group comprised three subgroups treated with low (0.1mg/kg; FS-L), medium (1.0mg/kg; FS-M) and high concentrations (10mg/kg; FS-H) of fluvastatin. Necrotic bone exposure was significantly lower in the FS-M (p=0.028) and FS-H (p=0.041) groups than in the MRONJ group. The distance between the edges of the epithelial surfaces was significantly shorter in the FS-M (p=0.042) and FS-H (p=0.041) groups. The area of necrotic bone and the necrotic bone ratio were significantly smaller in the FS-H group (p=0.041 and p=0.042 respectively). Bone volume fraction calculated on mu -CT images was significantly larger in the FS-H group than in the MRONJ group (p=0.021). Our findings suggest that a single local injection of fluvastatin following tooth extraction can potentially reduce the chance of developing MRONJ-like lesion in rats.