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Alcohol-Induced Bone Loss and Deficient Bone Repair

Alcohol-Induced Bone Loss and Deficient Bone Repair Dennis A. Chakkalakal* Alcoholism: Clinical and Experimental Research Volume 29, Issue 12, pages 2077–2090, December 2005 Keywords: Alcohol;Bone Remodeling;Bone Marrow;Fracture Healing;Osteogenic Differentiation Abstract: Background: Chronic consumption of excessive alcohol eventually results in an osteopenic skeleton and increased risk for osteoporosis. Alcoholics experience not only increased incidence of fractures from falls, but also delays in fracture healing compared with non-alcoholics. In this review the term “alcohol-induced bone disease” is used to refer to these skeletal abnormalities. Alcohol-induced osteopenia is distinct from osteoporoses such as postmenopausal osteoporosis and disuse osteoporosis. Gonadal insufficiency increases the rate of bone remodeling, whereas alcohol decreases this rate. Thus, histomorphometric studies show different characteristics for the bone loss that occurs in these two disease states. In particular, alcohol-induced osteopenia results mainly from decreased bone formation rather than increased bone resorption. Human, animal and cell culture studies of the effects of alcohol on bone strongly suggest alcohol has a dose-dependent toxic effect on osteoblast activity. The capacity of bone marrow stromal cells to differentiate into osteoblasts has a critical role in the cellular processes involved in the maintenance of the adult human skeleton by bone remodeling. Chronic alcohol consumption suppresses osteoblastic differentiation of bone marrow cells and promotes adipogenesis. In fracture healing, the effect of alcohol is to suppress synthesis of an ossifiable matrix, possibly due to inhibition of cell proliferation and maldifferentiation of mesenchymal cells in the repair tissue. This results in the deficient bone repair observed in animal studies, characterized by repair tissue of lower stiffness, strength and mineral content. Current knowledge of cellular effects and molecular mechanisms involved in alcohol-induced bone disease is insufficient to develop interventional strategies for its prevention and treatment. Objectives: The objectives of this review are 1) to identify the characteristics of alcohol-induced bone loss and deficient bone repair as revealed in human and animal studies, 2) to determine the current understanding of the cellular effects underlying both skeletal abnormalities, and 3) to suggest directions for future studies to resolve current ambiguities regarding the cellular basis of alcohol-induced bone disease. 过量饮酒可引起骨质流失 慢性的过量饮酒会最终引起骨骼的骨质流失,并增加罹患骨质疏松的风险。酒精不仅能增加由跌倒引起的骨折的概率,与正常非饮酒人员相比也会减缓骨折愈合的速率。本篇综述所用的“酒精引起的骨质流失”用来指代各种骨代谢紊乱。酒精诱导的骨质流失不同于绝经及废用型骨质流失。性激素不足会增加骨重建的速率,而酒精会减慢这一速率。因此,采用组织切片层面的研究就可以显示出这两种骨代谢疾病的差异。酒精诱导的骨质流失主要是作用于成骨细胞而不是破骨细胞。流行病学、动物水平及细胞水平研究表明酒精对于成骨细胞的活性有一剂量效应。骨髓间充质干细胞分化为成骨细胞的能力高低对于维持成年人类骨骼的正常骨重建平衡有着至关重要的作用。慢性饮酒会抑制骨髓间充质干细胞向成骨细胞分化的能力,增加其向脂肪细胞分化的能力。在骨折愈合过程中,酒精的作用是抑制骨基质矿化过程,这很可能就是因为抑制了修复组织中细胞增殖及分化能力所致。这就导致了在动物研究中所观察到的骨折不愈合,表现为待修复骨组织低的硬度、强度及矿物盐含量。目前的细胞及分子水平实验研究还不能得出介入性的阻止及治疗方法。






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Alcohol-Induced Bone Loss and Deficient Bone Repair Dennis A. Chakkalakal* Alcoholism: Clinical and Experimental Research Volume 29, Issue 12, pages

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