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骨质疏松症临床前研究:使用去卵巢绵羊的对比研究的系统评价。

Osteoporosis Preclinical Research: A Systematic Review on Comparative Studies Using Ovariectomized Sheep.

机构信息

Complex Structure Surgical Sciences and Technologies, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy.

Scientific Direction, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy.

出版信息

Int J Mol Sci. 2022 Aug 10;23(16):8904. doi: 10.3390/ijms23168904.

DOI:10.3390/ijms23168904
PMID:36012173
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9408715/
Abstract

Sheep ovariectomy (OVX) alone or associated to steroid therapy, deficient diet, or hypothalamic-pituitary disconnection has proven to be of critical importance for osteoporosis research in orthopedics. However, the impact of specific variables, such as breed, age, diet, time after OVX, and other variables, should be monitored. Thus, the design of comparative studies is mandatory to minimize the impact of these variables or to recognize the presence of unwanted variables as well as to better characterize bone remodeling in this model. Herein, we conducted a systematic review of the last 10 years on PubMed, Scopus, and Web of Knowledge considering only studies on OVX sheep where a control group was present. Of the 123 records screened, 18 studies were included and analyzed. Results showed that (i) Merino sheep are the most exploited breed; (ii) 5-6 years of age is the most used time for inducing OVX; (iii) ventral midline laparotomy is the most common approach to induce OVX; (iv) OVX associated to steroid therapy is the most widely used osteoporosis model; and (v) success of OVX was mostly verified 12 months after surgery. In detail, starting from 12 months after OVX a significant decline in bone mineral density and in microarchitectural bone parameters as well as in biochemical markers were detected in all studies in comparison to control groups. Bone alteration was also site-specific on a pattern as follows: lumbar vertebra, femoral neck, and ribs. Before 12 months from OVX and starting from 3-5 months, microarchitectural bone changes and biochemical marker alterations were present when osteoporosis was induced by OVX associated to steroid therapy. In conclusion, OVX in sheep influence bone metabolism causing pronounced systemic bone loss and structural deterioration comparable to the situation found in osteoporosis patients. Data for treating osteoporosis patients are based not only on good planning and study design but also on a correct animal use that, as suggested by 3Rs principles and by ARRIVE guidelines, includes the use of control groups to be directly contrasted with the experimental group.

摘要

绵羊卵巢切除术(OVX)单独或与类固醇治疗、饮食不足或下丘脑-垂体分离相结合,已被证明对骨科骨质疏松症研究具有重要意义。然而,应监测特定变量(如品种、年龄、饮食、OVX 后时间等)的影响。因此,必须进行比较研究的设计,以最大限度地减少这些变量的影响,或识别存在的不需要的变量,并更好地描述该模型中的骨重建。在此,我们在 PubMed、Scopus 和 Web of Knowledge 上进行了一项过去 10 年的系统性综述,仅考虑存在对照组的 OVX 绵羊研究。在筛选出的 123 条记录中,有 18 项研究被纳入并进行了分析。结果表明:(i)美利奴羊是最常用的品种;(ii)5-6 岁是诱导 OVX 最常用的时间;(iii)腹中线切开术是最常用的诱导 OVX 的方法;(iv)OVX 与类固醇治疗相结合是最广泛使用的骨质疏松症模型;(v)OVX 的成功大多在手术后 12 个月得到验证。具体而言,与对照组相比,所有研究在 OVX 后 12 个月开始时均检测到骨矿物质密度和微观结构骨参数以及生化标志物显著下降。骨改变也具有特定部位的特征,如下所示:腰椎、股骨颈和肋骨。在 OVX 后 12 个月之前,并且在 OVX 联合类固醇治疗诱导骨质疏松症的 3-5 个月开始时,就已经存在微观结构骨变化和生化标志物改变。总之,绵羊的 OVX 会影响骨代谢,导致明显的全身性骨质流失和结构恶化,与骨质疏松症患者的情况相当。治疗骨质疏松症患者的数据不仅基于良好的规划和研究设计,还基于正确的动物使用,正如 3R 原则和 ARRIVE 指南所建议的,包括使用对照组与实验组直接对比。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8306/9408715/a00b66916867/ijms-23-08904-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8306/9408715/e0e3b35d2ccb/ijms-23-08904-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8306/9408715/a00b66916867/ijms-23-08904-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8306/9408715/e0e3b35d2ccb/ijms-23-08904-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8306/9408715/f8dd03d59731/ijms-23-08904-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8306/9408715/78d57320fb82/ijms-23-08904-g003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8306/9408715/a00b66916867/ijms-23-08904-g005.jpg

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