Intermittent exposure to ethanol vapor affects osteoblast behaviour more severely than estrogen deficiency does

Torricelli, Paola; Fini, Milena; Giavaresi, Gianluca; Borsari, Veronica; Rimondini, Lia; Rimondini, R; Carrassi, Antonio; Giardino, Roberto

doi:10.1016/j.tox.2007.05.010

Cited by 18 publications

(9 citation statements)

References 70 publications

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“…Although differences in animal age and sex may account for these differences, a more likely explanation is that the binge-patterned high BALs achieved in the current study are more damaging to bone than lower BALs and cause a significant depression of bone formation activity not observed in previous studies. A recent study demonstrating that intermittent high-dose alcohol exposure by vapor inhalation also has significant detrimental effects on osteoblast function backs this supposition [23]. The acute or lower chronic alcohol doses given to rats in the studies mentioned above may indeed be leading to a positive effect on osteoblast function, as suggested by the osteocalcin data presented in these studies.…”

Section: Discussionmentioning

confidence: 76%

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

et al. 2009

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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-κβ (nuclear factor κβ) 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 rode...

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Section: Discussionmentioning

confidence: 76%

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

et al. 2009

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“…To this point, the only known long‐term pathology in postdependent rats is peripheral secondary osteoporosis (Torricelli et al . ), a condition that is commonly seen also in alcoholic patients (Kanis et al . ).…”

Section: Chronic Intermittent Exposure To Alcohol and The Postdependementioning

confidence: 99%

Postdependent state in rats as a model for medication development in alcoholism

Meinhardt

Sommer

2014

Addiction Biology

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Rational development of novel therapeutic strategies for alcoholism requires understanding of its underlying neurobiology and pathophysiology. Obtaining this knowledge largely relies on animal studies. Thus, choosing the appropriate animal model is one of the most critical steps in pre-clinical medication development. Among the range of animal models that have been used to investigate excessive alcohol consumption in rodents, the postdependent model stands out. It was specifically developed to test the role of negative affect as a key driving force in a perpetuating addiction cycle for alcoholism. Here, we will describe our approach to make rats dependent via chronic intermittent exposure to alcohol, discuss the validity of this model, and compare it with other commonly used animal models of alcoholism. We will summarize evidence that postdependent rats fulfill several criteria of a 'Diagnostic and Statistical Manual of Mental Disorders IV/V-like' diagnostic system. Importantly, these animals show long-lasting excessive consumption of and increased motivation for alcohol, and evidence for loss of control over alcohol intake. Our conclusion that postdependent rats are an excellent model for medication development for alcoholism is underscored by a summary of more than two dozen pharmacological tests aimed at reversing these abnormal alcohol responses. We will end with open questions on the use of this model. In the tradition of the Sanchis-Segura and Spanagel review, we provide comic strips that illustrate the postdependent procedure and relevant phenotypes in this review.

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“…Sun et al also found that insulin-like growth factor 1 (IGF-1) can prevent the inhibition of osteoblasts and counteract the ethanolinduced inhibition of proliferation [127]. In a study by Torricelli et al on osteoblasts isolated from trabecular bone of rats previously exposed to 7-week intermittent ethanol vapor (17 h/day; BAC, 150-350 mg/dL), it was reported that ethanol affects the osteoblast proliferation rate more than menopause does [128].…”

Section: Osteoblasts and Osteoclastsmentioning

confidence: 99%

Alcohol and bone: review of dose effects and mechanisms

et al. 2011

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Alcohol is widely consumed across the world. It is consumed in both social and cultural settings. Until recently, two types of alcohol consumption were recognized: heavy chronic alcohol consumption or light consumption. Today, there is a new pattern of consumption among teenagers and young adults namely: binge drinking. Heavy alcohol consumption is detrimental to many organs and tissues, including bones, and is known to induce secondary osteoporosis. Some studies, however, have reported benefits from light alcohol consumption on bone parameters. To date, little is known regarding the effects of binge drinking on bone health. Here, we review the effects of three different means of alcohol consumption: light, heavy, and binge drinking. We also review the detailed literature on the different mechanisms by which alcohol intake may decrease bone mass and strength. The effects of alcohol on bone are thought to be both direct and indirect. The decrease in bone mass and strength following alcohol consumption is mainly due to a bone remodeling imbalance, with a predominant decrease in bone formation. Recent studies, however, have reported new mechanisms by which alcohol may act on bone remodeling, including osteocyte apoptosis, oxidative stress, and Wnt signalling pathway modulation. The roles of reduced total fat mass, increased lipid content in bone marrow, and a hypoleptinemia are also discussed.

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Intermittent exposure to ethanol vapor affects osteoblast behaviour more severely than estrogen deficiency does

Cited by 18 publications

References 70 publications

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

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

Postdependent state in rats as a model for medication development in alcoholism

Alcohol and bone: review of dose effects and mechanisms

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