Dietary Essential Amino Acid Supplements Increase Bone Strength by Influencing Bone Mass and Bone Microarchitecture in Ovariectomized Adult Rats Fed an Isocaloric Low‐Protein Diet
作者:P. Ammann、A. Laib、J.‐P. Bonjour、J. M. Meyer、P. Rüegsegger、R. Rizzoli
DOI:10.1359/jbmr.2002.17.7.1264
日期:2002.7
This study was designed to investigate whether the administration of dietary essential amino acid supplements in adult rats made osteoporotic by estrogen deficiency and reduced protein intake could reverse the deleterious effects caused by these maneuvers. This animal model was selected to mimic the situation observed in elderly women in whom estrogen deficiency and/or low‐protein intake (but also calcium and vitamin D deficiency) are known to contribute to the pathogenesis of osteoporosis. Six‐month‐old rats were ovariectomized (OVX) and fed an isocaloric 2.5% casein diet for 10 weeks or sham‐operated (SHAM) and fed an isocaloric 15% casein diet. The animals fed the 2.5% casein diet were given isocaloric supplements of essential amino acids in similar relative proportion to that of casein at doses of 2.5% or 5% of total diet for an additional 16 weeks. Vertebrae, femur, and tibia bone mineral density (BMD); ultimate strength; and microtomographic histomorphometry were evaluated before and after dietary essential amino acid supplements. Essential amino acid supplements increased vertebrae, femur, and tibia bone strength in OVX rats fed a low‐protein diet. The mechanical changes induced by this dietary isocaloric supplement were associated with the prevention of a further BMD decrease or even with some increases and changes in microarchitecture such as from a rod to a plate trabecular spacial configuration and increased cortical thickness. Higher insulin‐like growth factor (IGF) I levels, as well as greater bone formation and reduced bone resorption as assessed by biochemical markers of bone remodeling, were found in rats receiving essential amino acid supplements. In conclusion, dietary essential amino acid supplements increased bone strength through modifications of BMD, trabecular architecture, and cortical thickness possibly by an IGF‐I‐mediated process.
本研究的目的是探究通过雌激素缺乏和蛋白质摄入量减少而导致骨质疏松的成年大鼠服用膳食必需氨基酸补充剂是否能逆转这些措施造成的有害影响。选择这种动物模型是为了模拟老年妇女的情况,众所周知,雌激素缺乏和/或蛋白质摄入量低(以及钙和维生素 D 缺乏)是导致骨质疏松症的发病机制。对六个月大的大鼠进行卵巢切除(OVX)并喂食2.5%酪蛋白等热量食物10周,或进行假手术(SHAM)并喂食15%酪蛋白等热量食物10周。喂食2.5%酪蛋白食物的动物还需再喂食16周等热量必需氨基酸补充剂,补充剂的相对比例与酪蛋白相似,剂量为食物总量的2.5%或5%。对膳食补充必需氨基酸前后的椎骨、股骨和胫骨骨矿物质密度(BMD)、极限强度和显微组织形态学进行了评估。补充必需氨基酸增加了以低蛋白饮食喂养的卵巢切除大鼠的椎骨、股骨和胫骨强度。这种等热量膳食补充剂引起的机械变化与防止骨密度进一步降低甚至增加以及微结构的变化有关,如从棒状变为板状的骨小梁空间结构和皮质厚度的增加。接受必需氨基酸补充剂的大鼠体内胰岛素样生长因子(IGF)I 水平较高,骨形成增加,骨重塑的生化指标评估显示骨吸收减少。总之,膳食必需氨基酸补充剂通过改变 BMD、骨小梁结构和皮质厚度来增加骨强度,这可能是由 IGF-I 介导的过程。