Department of Dental Clinic, Stomatology and Oral Pathology Sector, Federal University of Ceará, Fortaleza, Brazil.
Department of Dental Clinic, Stomatology and Oral Pathology Sector, Federal University of Ceará, Fortaleza, Brazil.
Arch Oral Biol. 2017 Nov;83:317-326. doi: 10.1016/j.archoralbio.2017.08.016. Epub 2017 Aug 30.
To evaluate the effects of dexamethasone (DEX) and nimesulide (NIM) on Bisphosphonate-related Osteonecrosis of the Jaw (BRONJ) in rats.
BRONJ was induced by zoledronic acid (ZA) infusion (0.2mg/kg) in Wistar rats (n=8), followed by extraction of the left lower first molar (BRONJ groups). Control groups (n=40) received saline (IV). For eight weeks, DEX (0.04, 0.4, 4mg/kg) or saline (SAL) were administered by gavage 24h before each infusion of ZA or saline (IV), or NIM (10.3mg/kg) was administered 24h and 12h before each infusion of ZA or saline (IV). The haematological analyses were conducted weekly. After euthanasia (day 70), the jaws were submitted to radiographic and microscopic analysis. Kidney, liver, spleen and stomach were analysed histopathologically.
The BRONJ groups showed a higher radiolucent area compared with the control groups (p<0.05). Histomorphometric analysis revealed healing and new bone formation in the control groups, while the BRONJ groups exhibited devitalized bone with bacterial colonies and inflammatory infiltrate. The BRONJ-DEX 0.4 and 4mg/kg groups had a greater number of bacterial colonies (p<0.05) and an increased polymorphonuclear cell count compared to the saline-BRONJ group, while the BRONJ-NIM group had a lower polymorphonuclear count (p<0.05). The BRONJ groups had leucocytosis, which was reduced by DEX administration. Treatments with DEX with or without ZA caused white pulp atrophy.
Thus, DEX or NIM therapy was not effective in preventing radiographic and histopathologic events associated with BRONJ. Treatment with DEX attenuated leucocytosis post-infusion with ZA.
评估地塞米松（DEX）和尼美舒利（NIM）对大鼠唑来膦酸相关性颌骨坏死（BRONJ）的影响。
通过唑来膦酸（ZA）输注（0.2mg/kg）在 Wistar 大鼠中诱导 BRONJ（n=8），然后拔除左侧下颌第一磨牙（BRONJ 组）。对照组（n=40）接受生理盐水（IV）。在 8 周内，DEX（0.04、0.4、4mg/kg）或生理盐水（SAL）通过灌胃给药，在每次 ZA 或生理盐水（IV）输注前 24 小时给药，或 NIM（10.3mg/kg）在每次 ZA 或生理盐水（IV）输注前 24 小时和 12 小时给药。每周进行血液学分析。安乐死后（第 70 天），颌骨进行放射照相和显微镜分析。对肾脏、肝脏、脾脏和胃进行组织病理学分析。
BRONJ 组与对照组相比，显示出更高的透光区（p<0.05）。组织形态计量学分析显示对照组有愈合和新骨形成，而 BRONJ 组则表现为骨失活，有细菌菌落和炎症浸润。BRONJ-DEX 0.4 和 4mg/kg 组的细菌菌落数量多于盐水-BRONJ 组（p<0.05），多形核细胞计数增加，而 BRONJ-NIM 组的多形核细胞计数较低（p<0.05）。BRONJ 组出现白细胞增多，DEX 给药后减少。DEX 治疗或不联合 ZA 治疗可导致白髓萎缩。
因此，DEX 或 NIM 治疗不能有效预防 BRONJ 相关的放射照相和组织病理学事件。DEX 治疗可减轻 ZA 输注后的白细胞增多。
