Abstract
Chronic alcohol abuse results in decreased bone mineral density (BMD), which can lead to increased fracture risk. In contrast, low levels of alcohol have been associated with increased BMD in epidemiological studies. Alcohol's toxic skeletal effects have been suggested to involve impaired vitamin D/calcium homeostasis. Therefore, dietary vitamin D supplementation may be beneficial in reducing bone loss associated with chronic alcohol consumption. Six-week-old female C57BL/6J mice were pair-fed ethanol (EtOH)-containing liquid diets (10 or 36% total calories) for 78 days. EtOH exposure at 10% calories had no effects on any measured bone or serum parameter. EtOH consumption at 36% of calories reduced BMD and bone strength (P < 0.05), decreased osteoblastogenesis, increased osteoclastogenesis, suppressed 1,25-hydroxyvitamin D3 [1,25(OH)2D3] serum concentrations (P < 0.05), and increased apoptosis in bone cells compared with pair-fed controls. In a second study, female mice were pair-fed 30% EtOH diets with or without dietary supplementation with vitamin D3 (cholecalciferol; VitD) for 40 days. VitD supplementation in the EtOH diet protected against cortical bone loss, normalized alcohol-induced hypocalcaemia, and suppressed EtOH-induced expression of receptor of nuclear factor-κB ligand mRNA in bone. In vitro, pretreatment of 1,25(OH)2D3 in osteoblastic cells inhibited EtOH-induced apoptosis. In EtOH/VitD mice circulating 1,25(OH)2D3 was lower compared with mice receiving EtOH alone (P < 0.05), suggesting increased sensitivity to feedback control of VitD metabolism in the kidney. These findings suggest dietary VitD supplementation may prevent skeletal toxicity in chronic drinkers by normalizing calcium homeostasis, preventing apoptosis, and suppressing EtOH-induced increases in bone resorption.
Footnotes
This work was supported by the National Institutes of Health National Institute on Alcohol Abuse and Alcoholism [Grant RO1 AA18282], the Arkansas Children's Hospital Research Institute Lyons Fund; and the Carl L. Nelson Chair in Orthopaedic Creativity, University of Arkansas for Medical Sciences.
Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
ABBREVIATIONS:
- BMD
- bone mineral density
- EtOH
- ethanol
- TEN
- total enteral nutrition
- VitD
- vitamin D3/cholecalciferol
- 25OHD3
- 25-hydroxyvitamin D3
- 1,25(OH)2D3
- 1,25-hydroxyvitamin D3
- PF
- pair-fed
- CT
- computed topography
- μCT
- micro-CT
- ROI
- regions of interest
- TRAP
- tartrate-resistant acid phosphatase
- CTX
- C-terminal telopeptide
- BEC
- blood ethanol concentration
- CV
- coefficient of variation
- PTH
- parathyroid hormone
- BV/TV
- bone volume/tissue volume
- VDR
- vitamin D receptor
- RANKL
- receptor of nuclear factor-κB ligand
- TUNEL
- terminal deoxynucleotidyl transferase dUTP nick-end labeling
- αMEM
- α-minimal essential medium
- FBS
- fetal bovine serum
- ANOVA
- analysis of variance
- PCR
- polymerase chain reaction.
- Received May 31, 2012.
- Accepted August 13, 2012.
- Copyright © 2012 by The American Society for Pharmacology and Experimental Therapeutics
JPET articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|