Alcohol-induced bone loss and deficient bone repair.
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.


OBJECTIVE
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.
Chakkalakal
Dennis A
DA
Orthopaedic Research Laboratory and Alcohol Research Center, Omaha Veterans Affairs Medical Center, Creighton University Biomedical Engineering Research Center and Department of Surgery, Omaha, Nebraska 68105, USA. DennisChakkalakal@med.va.gov
D000818:Animals; D001846:Bone Development / Q000187:drug effects*; D001851:Bone Diseases, Metabolic / Q000139:chemically induced* / Q000150:complications / Q000473:pathology; D001862:Bone Resorption / Q000473:pathology; D002492:Central Nervous System Depressants / Q000009:adverse effects*; D000431:Ethanol / Q000009:adverse effects*; D006801:Humans; D051381:Rats
D002492:Central Nervous System Depressants; D000431:Ethanol