Skeletal Biology Laboratory, School of Biological and Population Health Sciences, Oregon State University, Corvallis, OR, USA.
Alcohol Clin Exp Res. 2013 Aug;37(8):1271-7. doi: 10.1111/acer.12105. Epub 2013 Mar 29.
Chronic alcohol abuse is associated with increased risk of osteoporosis while light-to-moderate alcohol intake correlates with reduced osteoporosis risk. Addition of alcohol to a liquid diet is often used to model chronic alcohol abuse. Methods to model intermittent drinking (including binge drinking and light-to-moderate consumption) include (i) intragastric administration of alcohol by oral gavage or (ii) intraperitoneal (ip) administration of alcohol by injection. However, it is unclear whether the latter 2 methods produce comparable results. The purpose of this investigation was to determine the skeletal response to alcohol delivered daily by oral gavage or ip injection.
Ethanol (EtOH) or vehicle was administered to 4-month-old female Sprague-Dawley rats once daily at 1.2 g/kg body weight for 7 days. Following necropsy, bone formation and bone architecture were evaluated in tibial diaphysis (cortical bone) and proximal tibial metaphysis (cancellous bone) by histomorphometry. mRNA was measured for bone matrix proteins in distal femur metaphysis.
Administration of alcohol by gavage had no significant effect on body weight gain or bone measurements. In contrast, administration of the same dose of alcohol by ip injection resulted in reduced body weight, total suppression of periosteal bone formation in tibial diaphysis, decreased cancellous bone formation in proximal tibial metaphysis, and decreased mRNA levels for bone matrix proteins in distal femur.
Our findings raise concerns regarding the use of ip injection of EtOH in rodents as a method for modeling the skeletal effects of intermittent exposure to alcohol in humans. This concern is based on a failure of the ip route to replicate the oral route of alcohol administration.
慢性酒精滥用与骨质疏松风险增加相关,而轻度至中度饮酒与骨质疏松风险降低相关。在液体饮食中添加酒精通常用于模拟慢性酒精滥用。间歇性饮酒(包括 binge drinking 和轻度至中度饮酒)的建模方法包括(i)通过口服灌胃向胃内给予酒精,或(ii)通过腹腔内(ip)注射给予酒精。然而,目前尚不清楚后两种方法是否产生可比的结果。本研究的目的是确定通过口服灌胃或 ip 注射每日给予酒精对骨骼的影响。
将乙醇(EtOH)或载体以 1.2 g/kg 体重的剂量每日一次施用于 4 月龄雌性 Sprague-Dawley 大鼠,持续 7 天。解剖后,通过组织形态计量学评估胫骨骨干(皮质骨)和胫骨近端干骺端(松质骨)的骨形成和骨结构。测量股骨远端干骺端的骨基质蛋白的 mRNA。
通过灌胃给予酒精对体重增加或骨骼测量无显著影响。相比之下,以相同剂量的酒精通过 ip 注射给药会导致体重减轻、胫骨骨干的骨膜骨形成完全抑制、胫骨近端干骺端的松质骨形成减少以及股骨远端骨基质蛋白的 mRNA 水平降低。
我们的研究结果引发了对在啮齿动物中使用 ip 注射 EtOH 作为模拟人类间歇性暴露于酒精对骨骼影响的方法的关注。这种担忧基于 ip 途径未能复制口服途径给予酒精的情况。