IN VIVO STUDIES OF ETHANOL AGING AND OSTEOPENIA

乙醇老化和骨质减少的体内研究

• 批准号: 3422052
• 负责人: HORACE M PERRY
• 金额: $ 5.89万
• 依托单位: SAINT LOUIS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-03-01 至 1993-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3422052
• 关键词: aging; bone metabolism; dietary calcium; disease /disorder model; ethanol; gastrointestinal absorption /transport; histology; laboratory rat; male; nutrition related tag; osteoporosis; parathyroid hormones; pathologic bone resorption; vitamin D

Chronic ethanol ingestion is a major risk factor for osteoporosis, particularly in men. Osteoporosis in turn is a significant risk factor for a series of fractures, i.e. hip, vertebrae, Colles', with their attendant mortality and morbidity. The effect of ethanol is well documented in man and animal studies, particularly rodents. Rodent studies of bone disease, however, have limited application to adult human conditions because the epiphyses of most rodents remain-open until they die. Bone metabolism in animals with open epiphyses is thought to be much different than that in animals with closed epiphyses. This application seeks to examine the effect of chronic ethanol ingestion on the bone metabolism of a specific strain of aging rat (Fisher 344). This type of animal has documented closure of epiphyses at about fifteen months of age. In addition, other parameters of mineral metabolism, for example, calcium absorption, closely mimic those seen in aging man. Thus, the successful use of ethanol in this model with reduction in bone mass would establish this system as an appropriate model to study ethanol related loss of bone mass in man. The initial studies will examine the effect of varying amounts of ethanol on bone mass in elderly (21 month old) male F344 rats. Having established an optimal dietary ethanol level, long term studies of the effect of ethanol on the parameters of mineral metabolism will be undertaken. Serum and urine levels of calcium phosphate, creatinine, magnesium will be determined. Bone weight and mineral will be determined with non-decalcified histomorphometry studies of bone biology as well as osteoblast and osteoclast specific stains. Serum levels of calciotropic hormones, parathyroid hormone, 25 hydroxy and 1,25 dihydroxy vitamin D levels will be performed. The second year will examine strategies (primarily dietary) aimed at reducing or eliminating the bone loss seen in this model with ethanol ingestion. Parameters of mineral metabolism described above will be followed when appropriate. These studies should allow the establishment of the male Fisher 344 rats as an appropriate model to study alcohol related bone loss, as well as provide a preliminary indication of what if any disturbances in mineral metabolism occur and what if any dietary manipulations may alter them.

慢性酒精摄入是骨质疏松症的主要危险因素， 尤其是在男人身上。 骨质疏松症反过来是一个重要的危险因素， 一系列骨折，即髋关节、椎骨、科尔斯骨折， 死亡率和发病率。 乙醇对人体的影响已有充分的文献记载 和动物研究，特别是啮齿类动物。 啮齿类动物的骨病研究， 然而，其对成人条件的应用有限， 大多数啮齿类动物的骨骺在死亡前都是张开的。 骨代谢 骨骺开放的动物被认为与 骨骺闭合的动物。 本申请旨在审查 慢性酒精摄入对骨代谢的影响 老龄大鼠品系（Fisher 344）。 这种动物已经记录了 在大约15个月大时骨骺闭合。 此外，其他 矿物质代谢的参数，例如，钙的吸收，密切 因此，乙醇在这一领域的成功应用， 骨量减少的模型将使该系统成为一种 研究乙醇相关的人体骨量丢失的适当模型。 最初的研究将检查不同数量的乙醇的影响 对老年（21月龄）雄性F344大鼠骨量的影响。 建立了 一个最佳的饮食乙醇水平，长期研究的影响， 乙醇对矿物质代谢参数的影响。 血清 尿中磷酸钙肌酐镁的含量 测定 骨重量和矿物质将通过 骨生物学的非脱钙组织形态计量学研究以及 成骨细胞和破骨细胞特异性染色。 血清促钙素水平 激素、甲状旁腺激素、25羟基和1，25二羟基维生素D 水平将被执行。 第二年将审查战略（主要是饮食）， 减少或消除在该模型中用乙醇观察到的骨丢失 摄入 上述矿物质代谢的参数将是 在适当的时候跟进。 这些研究应允许建立雄性Fisher 344大鼠 作为研究酒精相关骨质流失的合适模型，以及 提供了一个初步的迹象，如果任何干扰矿物 代谢发生什么，如果任何饮食操纵可能会改变他们。