Binge Alcohol-Induced Bone Damage is Accompanied by Differential Expression of Bone Remodeling-Related Genes in Rat Vertebral Bone

Department of Orthopaedic Surgery and Rehabilitation, Loyola University Stritch School of Medicine, 2160 S. First Ave., Maywood, IL 60153, USA.
Calcified Tissue International (Impact Factor: 3.27). 04/2009; 84(6):474-84. DOI: 10.1007/s00223-009-9240-z
Source: PubMed


Binge alcohol-related bone damage is prevented by concurrent administration of bisphosphonates, suggesting an activation of bone resorption with patterned alcohol exposure. Although chronic alcohol abuse is known to cause osteopenia, little is known about the effects of binge drinking on bone metabolism. We examined the effects of binge alcohol exposure on the relationship between bone damage and modulation of bone remodeling-specific gene expression profiles. Our hypothesis was that bone damage observed in young adult rats after binge alcohol exposure is associated with differential expression of bone remodeling-related gene expression. We further hypothesized that this differential gene expression specific to bone remodeling (bone resorption or formation related) would be influenced by the duration of binge alcohol exposure. Binge alcohol (3 g/kg, i.p.) was administered on 3 consecutive days each week, for 1 or 4 weeks, to adult male rats. Matched control animals were injected with an equal volume of isotonic saline. Lumbar vertebrae, L4-5, were analyzed for the presence of bone damage by quantitative computed tomography and compressive strength analysis. Total RNA was isolated from an adjacent vertebrae (L3), and whole transcriptome gene expression data were obtained for each sample. The expression levels of a subset of bone formation and resorption-associated differentially expressed genes were validated by quantitative reverse transcriptase-polymerase chain reaction. Bone loss was not observed after 1 week of treatment but was observed after four binge alcohol cycles with a 23% decrease in cancellous bone mineral density and 17% decrease in vertebral compressive strength compared with control values (P < 0.05). We observed that the duration of binge alcohol treatment influenced the modulation of expression profiles for genes that regulate the bone formation process. The expression of key bone formation-related marker genes such as osteocalcin and alkaline phosphatase were significantly reduced (P < 0.05) after acute binge alcohol exposure, and expression of regulators of osteoblast activity such as bone morphogenetic proteins and parathyroid hormone receptor displayed significantly (P < 0.05) decreased differential expression. The expression of sclerostin, a key canonical Wnt inhibitory protein, was significantly increased after acute binge alcohol treatment. The expression of important regulators of osteoclast maturation and activity such as NF-kappabeta (nuclear factor kappabeta) ligand (RANKL) and interleukin-6 were significantly increased (P < 0.05) by binge alcohol, and osteoprotegerin levels were significantly decreased (P < 0.05) in vertebral bone. These results show that expression patterns of several key bone remodeling genes are significantly perturbed by binge alcohol treatment, suggesting that perturbation of gene expression associated with bone remodeling may be one mechanism contributing to the disruption of bone mass homeostasis and subsequent bone loss observed after binge alcohol exposure in rodents.

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    • "Intraperitoneal alcohol administration was made by receiving a single intraperitoneal injection of alcohol (20% v/v) in isotonic saline solution (3 g/Kg/d) (Callaci et al., 2009). Alcohol injections were given starting at 7:00 p.m., when the dark cycle began, for 3 consecutive days each week for 3 weeks. "
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    • "). Intraperitoneal injections and gavage are efficient methods for achieving high blood alcohol levels (BALs; Callaci et al., 2009), but these techniques are stressful for the animals and may lead to inflammation and necrosis of tissues. It is difficult to administer alcohol with these techniques for a long period of time (several months; Lieber et al., 1989). "
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    • "For example, individuals with a high risk of carcinogenesis should abstain from alcohol use [6]. Certain devastating chronic diseases such as heart disease [7–9], Alzheimer’s disease [10], stroke [11,12], liver disease [13–15], cancer [16–18], chronic respiratory disease [19,20], diabetes mellitus [21–23] and bone disease [24,25] may develop following chronic alcohol ingestion and contribute to the alcoholism-related high morbidity and mortality. In addition to chronic diseases, alcohol abuse may also trigger a cascade of acute health problems such as traffic accident-related injuries. "
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