The goal of the proposed research in rats is to examine the cellular and molecular mechanisms responsible for mediating alcohol's actions on bone and mineral metabolism. Chronic alcohol abuse is associated with depressed bone formation, osteopenia and increased fracture risk. The health risks for moderate drinkers are much less certain, but beneficial as well as detrimental effects have been described. A better understanding of the risks and benefits is important because the majority of our adult population are occasional to moderate drinkers. The hypotheses to be tested in these studies are that alcohol inhibits initiation of bone remodeling thereby reducing the overall rate of bone turnover. This action could benefit individuals with high bone turnover (e.g., women with postmenopausal bone loss). Additionally, we postulate that alcohol inhibits osteoblast activity during the bone formation phase of the bone remodeling cycle (this action could increase the risk for osteoporosis and is consistent with osteopenia observed with chronic alcohol abuse). At the molecular level, the changes in bone remodeling are postulated to result because alcohol disrupts expression of osteoblast-derived signaling peptides (skeletal growth factors and cytokines) which couple the site and amount of bone formation to the location and extent of bone resorption. These hypotheses will be tested in rats by establishing: 1) a dose response for the long-term effects of alcohol on bone mass, bone cell numbers and activities, architecture, osteoinductive activity, and mechanical properties; 2) short-term effects of alcohol on bone remodeling; 3) effects of alcohol on recruitment of osteoblasts and osteoclasts during bone remodeling; and 4) effects of alcohol on expression of genes related to osteoblast derived cell signaling peptides.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
5R01AA011140-05
Application #
6168334
Study Section
Special Emphasis Panel (SRCA (59))
Program Officer
Purohit, Vishnu
Project Start
1996-09-29
Project End
2001-08-31
Budget Start
2000-09-01
Budget End
2001-08-31
Support Year
5
Fiscal Year
2000
Total Cost
$197,926
Indirect Cost
Name
Mayo Clinic, Rochester
Department
Type
DUNS #
City
Rochester
State
MN
Country
United States
Zip Code
55905
Johnson, Teresa L; Gaddini, Gino; Branscum, Adam J et al. (2014) Effects of chronic heavy alcohol consumption and endurance exercise on cancellous and cortical bone microarchitecture in adult male rats. Alcohol Clin Exp Res 38:1365-72
Iwaniec, Urszula T; Turner, Russell T (2013) Intraperitoneal injection of ethanol results in drastic changes in bone metabolism not observed when ethanol is administered by oral gavage. Alcohol Clin Exp Res 37:1271-7
Marrone, Jill A; Maddalozzo, Gianni F; Branscum, Adam J et al. (2012) Moderate alcohol intake lowers biochemical markers of bone turnover in postmenopausal women. Menopause 19:974-9
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Iwaniec, Urszula T; Boghossian, St├ęphane; Trevisiol, Cynthia H et al. (2011) Hypothalamic leptin gene therapy prevents weight gain without long-term detrimental effects on bone in growing and skeletally mature female rats. J Bone Miner Res 26:1506-16
Turner, Russell T; Iwaniec, Urszula T (2011) Low dose parathyroid hormone maintains normal bone formation in adult male rats during rapid weight loss. Bone 48:726-32
Turner, R T; Iwaniec, U T (2010) Moderate weight gain does not influence bone metabolism in skeletally mature female rats. Bone 47:631-5
Menagh, Philip J; Turner, Russell T; Jump, Donald B et al. (2010) Growth hormone regulates the balance between bone formation and bone marrow adiposity. J Bone Miner Res 25:757-68
Turner, Russell T; Rosen, Clifford J; Iwaniec, Urszula T (2010) Effects of alcohol on skeletal response to growth hormone in hypophysectomized rats. Bone 46:806-12
Maddalozzo, G F; Turner, R T; Edwards, C H T et al. (2009) Alcohol alters whole body composition, inhibits bone formation, and increases bone marrow adiposity in rats. Osteoporos Int 20:1529-38

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