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.
