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肥胖影响 Wistar 大鼠双膦酸盐诱导性骨坏死的发展。

Obesity influences the development of bisphosphonate-induced osteonecrosis in Wistar rats.

机构信息

Universidade Federal da Paraíba, Centro de Ciências da Saúde, Programa de Pós-Graduação em Odontologia, João Pessoa, Paraíba, Brasil.

Universidade Federal da Paraíba, Centro de Ciências da Saúde, Programa de Pós-Graduação em Produtos Naturais e Sintéticos Bioativos, João Pessoa, Paraíba, Brasil.

出版信息

J Appl Oral Sci. 2023 Sep 25;31:e20230133. doi: 10.1590/1678-7757-2023-0133. eCollection 2023.

DOI:10.1590/1678-7757-2023-0133
PMID:37792808
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10547385/
Abstract

Medication-related osteonecrosis of the jaw (MRONJ) is characterized by bone exposure for more than eight weeks in patients who have used or been treated with antiresorptive or antiangiogenic drugs, without a history of radiation therapy or metastatic diseases in the jaws. Obesity is associated with changes in periodontal tissues and oral microbiota that are linked to bone alterations. This study aimed to analyze the influence of obesity on the development of bisphosphonate-induced osteonecrosis. The experiment randomly and simply divided 24 male Wistar rats (Rattus norvegicus) into four groups: healthy, with osteonecrosis, obese, and obese with osteonecrosis (n=6 per group). Osteonecrosis was induced through weekly intraperitoneal injection for eight weeks at a dose of 250 µg/kg of zoledronic acid in a 4 mg/5 mL solution, combined with trauma (exodontia). Obesity was induced through a high glycaemic index diet. Each group was qualitatively and quantitatively evaluated regarding the development of models and pathological anatomy of the lesions. The results were expressed in mean percentage and standard deviation and statistically analyzed using one-way analysis of variance (ANOVA) followed by Tukey's post-hoc test, with a significance level of 5% (p<0.05) to establish differences found between the groups. Animals in the osteonecrosis group and the obese with osteonecrosis group presented larger necrosis areas (averages: 172.83±18,19 µm2 and 290.33±15,77 µm2, respectively) (p<0,0001). Bone sequestration, hepatic steatosis, and increased adipocyte size were observed in the obese group (average: 97.75±1.91 µm2) and in the obese with osteonecrosis group (average: 98.41±1.56 µm2), indicating greater tissue damage in these groups (p<0,0001). All parameters analyzed (through histological, morphometric, and murinometric analyses) increased for the obese and obese with osteonecrosis groups, suggesting a possible influence of obesity on the results. However, further studies are needed to confirm the role of obesity in the possible exacerbation of osteonecrosis and understand the underlying mechanisms.

摘要

药物相关性下颌骨坏死(MRONJ)的特征为在使用或接受抗吸收或抗血管生成药物治疗的患者中,骨暴露超过 8 周,且无颌骨放射治疗或转移疾病史。肥胖与牙周组织和口腔微生物群的变化有关,这些变化与骨改变有关。本研究旨在分析肥胖对双膦酸盐诱导性骨坏死发展的影响。该实验随机且简单地将 24 只雄性 Wistar 大鼠(Rattus norvegicus)分为四组:健康组、坏死组、肥胖组和肥胖伴坏死组(每组 6 只)。通过每周腹腔注射唑来膦酸(剂量为 250 µg/kg,溶于 4mg/5mL 溶液中)诱导坏死 8 周,同时进行创伤(拔牙)。通过高血糖指数饮食诱导肥胖。对每组模型的发展和病变的病理解剖进行定性和定量评估。结果以平均值和标准差表示,并使用单因素方差分析(ANOVA)进行统计分析,随后进行 Tukey 事后检验,以 5%的显著性水平(p<0.05)确定组间差异。坏死组和肥胖伴坏死组的动物表现出更大的坏死面积(平均值分别为 172.83±18,19 µm2 和 290.33±15,77 µm2)(p<0.0001)。肥胖组(平均值为 97.75±1.91 µm2)和肥胖伴坏死组(平均值为 98.41±1.56 µm2)观察到骨隔离、肝脂肪变性和脂肪细胞增大,表明这些组的组织损伤更大(p<0.0001)。肥胖组和肥胖伴坏死组的所有分析参数(通过组织学、形态计量学和鼠计量学分析)均增加,提示肥胖可能对结果有影响。然而,需要进一步的研究来确认肥胖在可能加剧骨坏死中的作用,并了解潜在的机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7906/10547385/52c08df5521a/1678-7757-jaos-31-e20230133-gf08.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7906/10547385/3a160f48e288/1678-7757-jaos-31-e20230133-gf01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7906/10547385/d5278ef24ce1/1678-7757-jaos-31-e20230133-gf02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7906/10547385/a08c747e947a/1678-7757-jaos-31-e20230133-gf03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7906/10547385/0a844c161908/1678-7757-jaos-31-e20230133-gf04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7906/10547385/5151347f8d07/1678-7757-jaos-31-e20230133-gf05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7906/10547385/35b87f1bcdd1/1678-7757-jaos-31-e20230133-gf06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7906/10547385/6ea6331a9f2a/1678-7757-jaos-31-e20230133-gf07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7906/10547385/52c08df5521a/1678-7757-jaos-31-e20230133-gf08.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7906/10547385/3a160f48e288/1678-7757-jaos-31-e20230133-gf01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7906/10547385/d5278ef24ce1/1678-7757-jaos-31-e20230133-gf02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7906/10547385/a08c747e947a/1678-7757-jaos-31-e20230133-gf03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7906/10547385/0a844c161908/1678-7757-jaos-31-e20230133-gf04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7906/10547385/5151347f8d07/1678-7757-jaos-31-e20230133-gf05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7906/10547385/35b87f1bcdd1/1678-7757-jaos-31-e20230133-gf06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7906/10547385/6ea6331a9f2a/1678-7757-jaos-31-e20230133-gf07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7906/10547385/52c08df5521a/1678-7757-jaos-31-e20230133-gf08.jpg

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