Voluntary Chronic Heavy Alcohol Consumption in Male Rhesus Macaques Suppresses Cancellous Bone Formation and Increases Bone Marrow Adiposity.

Abstract

BACKGROUND\nChronic heavy alcohol consumption is an established risk factor for bone fracture but comorbidities associated with alcohol intake may contribute to increased fracture rates in alcohol abusers. To address the specific effects of alcohol on bone, we used a non-human primate model and evaluated voluntary alcohol consumption on (1) global markers of bone turnover in blood and (2) cancellous bone mass, density, microarchitecture, turnover and microdamage in lumbar vertebra.\n\n\nMETHODS\nFollowing a 4-month induction period, 6-year-old male rhesus macaques (Macaca mulatta, n=13) voluntarily self-administered water or ethanol (4% w/v) for 22 h/d, 7 d/wk for a total of 12 months. Control animals (n=9) consumed an isocaloric maltose-dextrin solution. Tetracycline hydrochloride was administered orally 17 and 3 days prior to sacrifice to label mineralizing bone surfaces. Global skeletal response to ethanol was evaluated by measuring plasma osteocalcin and carboxy-terminal collagen crosslinks (CTX). Local response was evaluated in lumbar vertebra using dual energy X-ray absorptiometry, microcomputed tomography, static and dynamic histomorphometry, and histological assessment of microdamage.\n\n\nRESULTS\nMonkeys in the ethanol group consumed an average of 2.8±0.2 (mean±SE) g/kg/d of ethanol (30±2% of total Calories) resulting in an average blood ethanol concentration of 88.3±8.8 mg/dl 7 hours after the session onset. Plasma CTX and osteocalcin tended to be lower in ethanol-consuming monkeys compared to controls. Significant differences in bone mineral density in lumbar vertebrae 1-4 were not detected with treatment. However, cancellous bone volume fraction (in cores biopsied from the central region of the 3rd vertebral body) was lower in ethanol-consuming monkeys compared to controls. Furthermore, ethanol-consuming monkeys had lower osteoblast perimeter and mineralizing perimeter, no significant difference in osteoclast perimeter, and higher bone marrow adiposity than controls. No significant differences between groups were detected in microcrack density (2nd lumbar vertebra).\n\n\nCONCLUSIONS\nVoluntary chronic heavy ethanol consumption reduces cancellous bone formation in lumbar vertebra by decreasing osteoblast-lined bone perimeter, a response associated with an increase in bone marrow adiposity.