Department of Kinesiology, Brock University, St. Catharines, ON, Canada.
Centre for Bone and Muscle Health, Brock University, St. Catharines, ON, Canada.
J Bone Miner Res. 2023 Jan;38(1):198-213. doi: 10.1002/jbmr.4740. Epub 2022 Dec 5.
Osteoporosis has traditionally been characterized by underlying endocrine mechanisms, though evidence indicates a role of inflammation in its pathophysiology. Lipopolysaccharide (LPS), a component of gram-negative bacteria that reside in the intestines, can be released into circulation and stimulate the immune system, upregulating bone resorption. Exogenous LPS is used in rodent models to study the effect of systemic inflammation on bone, and to date a variety of different doses, routes, and durations of LPS administration have been used. The study objective was to determine whether systemic administration of LPS induced inflammatory bone loss in rodent models. A systematic search of Medline and four other databases resulted in a total of 110 studies that met the inclusion criteria. Pooled standardized mean differences (SMDs) and corresponding 95% confidence intervals (CI) with a random-effects meta-analyses were used for bone volume fraction (BV/TV) and volumetric bone mineral density (vBMD). Heterogeneity was quantified using the I statistic. Shorter-term (<2 weeks) and longer-term (>2 weeks) LPS interventions were analyzed separately because of intractable study design differences. BV/TV was significantly reduced in both shorter-term (SMD = -3.79%, 95% CI [-4.20, -3.38], I 62%; p < 0.01) and longer-term (SMD = -1.50%, 95% CI [-2.00, -1.00], I 78%; p < 0.01) studies. vBMD was also reduced in both shorter-term (SMD = -3.11%, 95% CI [-3.78, -2.44]; I 72%; p < 0.01) and longer-term (SMD = -3.49%, 95% CI [-4.94, -2.04], I 82%; p < 0.01) studies. In both groups, regardless of duration, LPS negatively impacted trabecular bone structure but not cortical bone structure, and an upregulation in bone resorption demonstrated by bone cell staining and serum biomarkers was reported. This suggests systemically delivered exogenous LPS in rodents is a viable model for studying inflammatory bone loss, particularly in trabecular bone. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
骨质疏松症传统上以潜在的内分泌机制为特征，尽管有证据表明炎症在其病理生理学中起作用。脂多糖（LPS）是存在于肠道中的革兰氏阴性细菌的组成部分，可以释放到循环中并刺激免疫系统，上调骨吸收。外源性 LPS 用于啮齿动物模型研究全身炎症对骨骼的影响，迄今为止，已经使用了各种不同的 LPS 给药剂量、途径和持续时间。本研究旨在确定全身给予 LPS 是否会在啮齿动物模型中引起炎症性骨丢失。通过对 Medline 和其他四个数据库的系统检索，共纳入了 110 项符合纳入标准的研究。使用随机效应荟萃分析计算骨体积分数（BV/TV）和体积骨矿物质密度（vBMD）的标准化均数差（SMD）和相应的 95%置信区间（CI）。使用 I 统计量量化异质性。由于研究设计的差异难以解决，因此分别分析了短期（<2 周）和长期（>2 周） LPS 干预。BV/TV 在短期（SMD=-3.79%，95%CI[-4.20，-3.38]，I 62%；p<0.01）和长期（SMD=-1.50%，95%CI[-2.00，-1.00]，I 78%；p<0.01）研究中均显著降低。短期（SMD=-3.11%，95%CI[-3.78，-2.44]；I 72%；p<0.01）和长期（SMD=-3.49%，95%CI[-4.94，-2.04]，I 82%；p<0.01）研究中 vBMD 也降低。在这两组中，无论 LPS 的持续时间如何，它都对小梁骨结构产生负面影响，但对皮质骨结构没有影响，并且通过骨细胞染色和血清生物标志物报告了骨吸收的上调。这表明在啮齿动物中全身给予外源性 LPS 是研究炎症性骨丢失的可行模型，特别是在小梁骨中。
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