Twelve months of voluntary heavy alcohol consumption in male rhesus macaques suppresses intracortical bone remodeling

Gaddini, Gino W.; Grant, Kathleen A.; Woodall, Andrew; Stull, Cara; Maddalozzo, Gianni F.; Zhang, Bo; Turner, Russell T.; Iwaniec, Urszula T.

doi:10.1016/j.bone.2014.10.025

Cited by 30 publications

(31 citation statements)

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“…We also reported region-specific changes in mucosal tissue gene expression and microbial composition with CD (22). Additional studies using this cohort of macaques have reported suppression of intracortical bone remodeling (23) as well as gene expression and DNA methylation pattern changes in the brain associated with CD (24)(25)(26). Here, we examined the impact of CD on the transcriptional profiles and functional responses of LPLs isolated from the duodenum, jejunum, ileum, and colon in presence or absence of phorbol myristate acetate (PMA) and ionomycin stimulation.…”

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confidence: 60%

Chronic ethanol consumption alters lamina propria leukocyte response to stimulation in a region‐dependent manner

et al. 2019

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Chronic heavy alcohol consumption, also referred to as chronic heavy drinking (CHD), results in intestinal injury characterized by increased permeability, dysbiosis, nutrient malabsorption, potentially higher susceptibility to infection, and increased risk of colorectal cancer. However, our understanding of the mechanisms by which CHD results in intestinal damage remains incomplete. Here, we investigated the impact of chronic drinking on transcriptional and functional responses of lamina propria leukocytes (LPLs) isolated from the 4 major gut sections. Although no significant differences were detected between LPLs isolated from the ethanol and control groups at resting state within each major gut section, our analysis uncovered key regional differences in composition and function of LPLs independent of alcohol consumption. However, in response to phorbol myristate acetate and ionomycin, duodenal LPLs from ethanol‐drinking animals generated a dampened response, whereas jejunal and ileal LPLs from ethanol‐drinking animals produced a heightened response. Transcriptional responses following stimulation were pronounced in ileal and duodenal LPLs from the ethanol‐drinking group but less evident in jejunal and colonic LPLs compared with controls, suggesting a more significant impact of alcohol on these gut regions. The altered intestinal LPL function detected in our study reveals remarkable region specificity and novel insight into potential mechanisms of intestinal injury associated with CHD.—Barr, T., Lewis, S. A., Sureshchandra, S., Doratt, B., Grant, K. A., Messaoudi, I. Chronic ethanol consumption alters lamina propria leukocyte response to stimulation in a region‐dependent manner. FASEB J. 33, 7767–7777 (2019). http://www.fasebj.org

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Chronic ethanol consumption alters lamina propria leukocyte response to stimulation in a region‐dependent manner

et al. 2019

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“…Our failure to detect a reduction in BMD in the present study differs from the reduction typically observed in young rodents where alcohol inhibited bone growth (Maurel et al., ), and suggests that although alcohol resulted in a negative turnover balance in the young adult male monkeys, the duration of exposure was insufficient to detect changes with DXA. Alternatively, reduced cortical porosity (Gaddini et al., ) may have compensated for reduced bone volume fraction in the cancellous compartment, resulting in no net change in BMD.…”

Section: Discussionmentioning

confidence: 99%

“…The experimental protocol is described in detail elsewhere (Gaddini et al., ; Grant et al., ). In brief, the protocol consisted of an induction phase (120 days) and a voluntary drinking phase (12 months).…”

Section: Methodsmentioning

confidence: 99%

“…Studies conducted in rats have demonstrated detrimental effects of high levels of alcohol consumption on bone accrual during growth (Court‐Brown et al., ; Gaddini et al., ; Turner et al., ). The few rodent studies performed following skeletal maturity suggest that chronic consumption of high levels of alcohol results in bone loss and decreased bone strength (Gaddini et al., ; Hogan et al., ; Turner et al., ). A 16‐week alcohol intervention study performed in skeletally mature (8‐month‐old) female rats identified a dose–response suppression in bone formation.…”

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confidence: 99%

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

Kahler‐Quesada

Grant

Walter

et al. 2019

Alcoholism Clin & Exp Res

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Background: Chronic 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 nonhuman primate model and evaluated voluntary alcohol consumption on: (i) global markers of bone turnover in blood and (ii) cancellous bone mass, density, microarchitecture, turnover, and microdamage in lumbar vertebra.Methods: Following a 4-month induction period, 6-year-old male rhesus macaques (Macaca mulatta, n = 13) voluntarily self-administered water or ethanol (EtOH; 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 EtOH was evaluated by measuring plasma osteocalcin and carboxyterminal collagen cross-links (CTX). Local response was evaluated in lumbar vertebra using dualenergy X-ray absorptiometry, microcomputed tomography, static and dynamic histomorphometry, and histological assessment of microdamage.Results: Monkeys in the EtOH group consumed an average of 2.8 AE 0.2 (mean AE SE) g/kg/d of EtOH (30 AE 2% of total calories), resulting in an average blood EtOH concentration of 88.3 AE 8.8 mg/ dl 7 hours after the session onset. Plasma CTX and osteocalcin tended to be lower in EtOH-consuming monkeys compared to controls. Significant differences in bone mineral density in lumbar vertebrae 1 to 4 were not detected with treatment. However, cancellous bone volume fraction (in cores biopsied from the central region of the third vertebral body) was lower in EtOH-consuming monkeys compared to controls. Furthermore, EtOH-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 (2 nd lumbar vertebra).Conclusions: Voluntary chronic heavy EtOH consumption reduces cancellous bone formation in lumbar vertebra by decreasing osteoblast-lined bone perimeter, a response associated with an increase in bone marrow adiposity.

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“…Serum EtOH was measured at necropsy as described (Gaddini et al., ). Serum CTX‐1 and osteocalcin were measured using standard ELISA.…”

Section: Methodsmentioning

confidence: 99%

Effects of Alcohol and Estrogen Receptor Blockade Using ICI 182,780 on Bone in Ovariectomized Rats

Wagner

Howe

Philbrick

et al. 2019

Alcoholism Clin & Exp Res

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Background: Estrogen signaling is essential for the sexual dimorphism of the skeleton, is required for normal bone remodeling balance in adults, and may influence the skeletal response to alcohol. High levels of alcohol consumption lower bone mass in ovary-intact but not ovariectomized (ovx) rats. However, the extremely rapid rate of bone loss immediately following ovx may obscure the effects of alcohol. We therefore determined (i) whether heavy alcohol consumption (35% caloric intake) influences bone in sexually mature ovx rats with established cancellous osteopenia and (ii) whether ICI 182,780 (ICI), a potent estrogen receptor signaling antagonist, alters the skeletal response to alcohol.Methods: Three weeks following ovx, rats were randomized into 5 groups, (i) baseline, (ii) control + vehicle, (iii) control + ICI, (iv) ethanol (EtOH) + vehicle, or (v) EtOH + ICI, and treated accordingly for 4 weeks. Dual-energy X-ray absorptiometry, microcomputed tomography, blood measurements of markers of bone turnover, and gene expression in femur and uterus were used to evaluate response to alcohol and ICI.Results: Rats consuming alcohol had lower bone mass and increased fat mass. Bone microarchitecture of the tibia and gene expression in femur were altered; specifically, there was reduced accrual of cortical bone, net loss of cancellous bone, and differential expression of 19/84 genes related to bone turnover. Furthermore, osteocalcin, a marker of bone turnover, was lower in alcohol-fed rats. ICI had no effect on weight gain, body composition, or cortical bone. ICI reduced cancellous bone loss and serum CTX-1, a biochemical marker of bone resorption; alcohol antagonized the latter 2 responses. Neither alcohol nor ICI affected uterine weight or gene expression.Conclusions: Alcohol exaggerated bone loss in ovx rats in the presence or absence of estrogen receptor blockade with ICI. The negligible effect of alcohol on uterus and limited effects of ICI on bone in alcohol-fed ovx rats suggest that estrogen receptor signaling plays a limited role in the action of alcohol on bone in a rat model for chronic alcohol abuse.

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Twelve months of voluntary heavy alcohol consumption in male rhesus macaques suppresses intracortical bone remodeling

Cited by 30 publications

References 74 publications

Chronic ethanol consumption alters lamina propria leukocyte response to stimulation in a region‐dependent manner

Chronic ethanol consumption alters lamina propria leukocyte response to stimulation in a region‐dependent manner

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

Effects of Alcohol and Estrogen Receptor Blockade Using ICI 182,780 on Bone in Ovariectomized Rats

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