Abstract：
Osteonecrosis of the jaw (ONJ) is a relatively rare side effect after prolonged use of bisphosphonates, which are drugs used to treat bone resorption in osteoporosis and certain cancers. This study introduces a novel ONJ model in rats by combining exposure to bisphosphonates, oral surgery, and bacterial inoculation. Potential ONJ preventive effects of polyguanidine (GuaDex) or antibiotics were evaluated. The study consisted of twenty-four male Wistar rats were divided into four groups. Groups 1 to 3 were given weekly doses of i.v. Zoledronic acid (ZA), four weeks before and two weeks after an osteotomy procedure on their left mandibular first molar. Group 4 was a negative control. Streptococcus gordonii bacteria were introduced into the osteotomy pulp chamber and via the food for seven days. On day eight, the rats were given different treatments. Group 1 was given a GuaDex injection into the osteotomy socket, Group 2 was given an intramuscular (i.m.) injection of clindamycin, Group 3 (positive control) was given an i.m. injection of saline, and Group 4 was given an i.m. injection of saline. Blood samples were taken two weeks after the osteotomy procedure, after which the rats were euthanized. Bone healing, bone mineral density, histology, and blood status were analyzed. The results showed that Group 1 (GuaDex) had no ONJ, extensive ongoing bone regeneration, active healing activity, vascularization, and no presence of bacteria. Group 2 (clindamycin) showed early stages of ONJ, avascular areas, and bacteria. Group 3 showed stages of ONJ, inflammatory infiltrates, defective healing, and bacterial presence, and Group 4 had normal healing activity and no bacterial presence. Conclusion: ZA treatment and bacterial inoculation after tooth extraction inhibited bone remodeling/healing and induced ONJ characteristic lesions in the rats. Only GuaDex apparently prevented ONJ development, stimulated bone remodeling, and provided an antimicrobial effect.
摘要：
长时间使用双膦酸盐后，颌骨坏死（ONJ）是一种相对罕见的副作用，用于治疗骨质疏松症和某些癌症的骨吸收的药物。这项研究介绍了一种新的大鼠ONJ模型，通过结合暴露于双膦酸盐，口腔外科,和细菌接种。评估了多胍（GuaDex）或抗生素的潜在ONJ预防作用。该研究由24只雄性Wistar大鼠组成，分为四组。第1组至第3组给予每周剂量的唑来膦酸（ZA），左下颌第一磨牙截骨手术前四周和术后两周。第4组为阴性对照。将格氏链球菌引入截骨牙髓室并通过食物放置7天。在第八天，对大鼠进行不同的处理。第1组给予GuaDex注射入截骨窝，第2组给予肌内（i.m.）注射克林霉素，第3组(阳性对照)静脉注射生理盐水,第4组给予生理盐水i.m.注射。截骨手术后两周采集血样，之后对大鼠实施安乐死。骨愈合,骨矿物质密度，组织学,并对血液状态进行分析。结果显示，第1组（GuaDex）没有ONJ，广泛持续的骨再生，积极的治疗活动，血管化,也没有细菌的存在.第2组（克林霉素）显示早期的ONJ，无血管区域,和细菌。第3组显示ONJ阶段，炎性浸润，有缺陷的愈合，和细菌的存在，第4组具有正常的愈合活性并且没有细菌存在。结论：拔牙后ZA处理和细菌接种抑制了大鼠的骨重建/愈合，并引起了ONJ特征性病变。只有GuaDex显然阻止了ONJ的开发，刺激骨骼重建，并提供抗菌作用。
