Skip to main content

Advertisement

SpringerLink
Log in

Effects of Nutrition and Alcohol Consumption on Bone Loss

  • Published:
Current Osteoporosis Reports Aims and scope Submit manuscript

Abstract

It is well established that excessive consumption of high-fat diets results in obesity. However, the consequences of obesity on skeletal development, maturation, and remodeling have been the subject of controversy. New studies suggest that the response of the growing skeleton to mechanical loading is impaired and trabecular bone mass is decreased in obesity and after high-fat feeding. At least in part, this occurs as a direct result of inhibited Wnt signaling and activation of peroxisome proliferator-activated receptor-γ (PPAR-γ) pathways in mesenchymal stem cells by fatty acids. Similar effects on Wnt and PPAR-γ signaling occur after chronic alcohol consumption as the result of oxidative stress and result in inhibited bone formation accompanied by increased bone marrow adiposity. Alcohol-induced oxidative stress as the result of increased NADPH-oxidase activity in bone cells also results in enhanced RANKL-RANK signaling to increase osteoclastogenesis. In contrast, consumption of fruits and legumes such as blueberries and soy increase bone formation. New data suggest that Wnt and bone morphogenetic protein signaling pathways are the molecular targets for bone anabolic factors derived from the diet.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Reid IR. Fat and bone. Arch Biochem Biophys. 2010;503:20–7.

    Article  PubMed  CAS  Google Scholar 

  2. Kawai M, Rosen CJ. Adiposity and bone accrual—still an established paradigm? Nat Revs Endocrinol. 2010;6:63–4.

    Article  Google Scholar 

  3. Westendorf JJ, Kahler RA, Schroeder TM. Wnt signaling in osteoblasts and bone diseases. Gene. 2004;341:19–39.

    Article  PubMed  CAS  Google Scholar 

  4. Canalis E, Economides AN, Gazzerro E. Bone morphogenic proteins, their antagonists, and the skeleton. Endocr Rev. 2003;24:218–35.

    Article  PubMed  CAS  Google Scholar 

  5. Lecka-Czernik B. PPARs in bone: the role in bone cell differentiation and regulation of energy metabolism. Curr Osteoporos Rep. 2010;8:84–90.

    Article  PubMed  Google Scholar 

  6. Lee J-L, Kim H-N, Yang D, et al. Trolox prevents osteoclastogenesis by suppressing RANKL-Expression and Signaling. J Biol Chem. 2009;284:13725–34.

    Article  PubMed  CAS  Google Scholar 

  7. Almeida M, Han L, Martin-Millan M, et al. Skeletal involution by age-associated oxidative stress and its acceleration by loss of sex steroids. J Biol Chem. 2007;27285–97.

  8. Almeida M, Han L, Ambrogini E, et al. Oxidative stress stimulates apoptosis and activates NF-kappaB in osteoblastic cells via a PKCbeta/p66shc signaling cascade: counter regulation by estrogens or androgens. Mol Endocrinol. 2010;24:2030–7.

    Article  PubMed  CAS  Google Scholar 

  9. Manolagas SC. From estrogen-centric to aging and oxidative stress: a revised perspective of the pathogenesis of oesteoporosis. Endocr Rev. 2010;31:266–300.

    Article  PubMed  CAS  Google Scholar 

  10. Fu X, Ma X, Lu H, et al. Associations of fat mass and fat distribution with bone mineral density in pre- and post-menopausal Chinese women. Osteoporos Int. 2010;(In Press).

  11. von Muhlen D, Safil S, Jassai SK, et al. Associations between metabolic syndrome and bone health in older men and women: the Rancho Bernado study. Osteoporos Int. 2007;18:1337–44.

    Article  Google Scholar 

  12. •• Dimitri P, Wales JK, Bishop N. Fat and bone in children: differential effects of obesity on bone size and mass according to fracture history. J Bone Min Res 2010;25:527–36. This article links increased fracture risk in children with obesity and suggests that obesity prevents the normal skeletal response to mechanical loading.

    Article  PubMed  Google Scholar 

  13. Karsenty G, Oury F. The central regulation of bone mass, the frist link between bone remodeling and energy metabolism. J Clin Endocrinol Metab. 2010;95:4795–801.

    Article  PubMed  CAS  Google Scholar 

  14. • Dimitri P, Wales JK, Bishop N. Adipokines, bone derived factors and bone turnover in obese children; evidence of altered fat-bone signaling resulting in reduced bone mass. Bone. 2010;(In Press). This article demonstrates correlations between increased serum leptin and increased bone resorption and between reduced serum adiponectin and increased levels of the soluble Wnt inhibitor Dickkopf-1 in obese children.

  15. Cao JJ, Gregoire BR, Gao H. High fat diet decreases cancellous bone mass but has no effect on cortical bone mass in the tibia in mice. Bone. 2009;44:1097–104.

    Article  PubMed  CAS  Google Scholar 

  16. Kyung TW, Lee JE, Phan TV, et al. Osteoclastogenesis by bone marrow-derived macrophages is enhanced in obese mice. J Nutr. 2009;139:502–6.

    Article  PubMed  CAS  Google Scholar 

  17. Graham LS, Tintut Y, Parhami F, et al. Bone density of hyperlipidemia: the T lymphocyte connection. J Bone Miner Res. 2010;25:2460–9.

    Article  PubMed  CAS  Google Scholar 

  18. •• Chen J-R, Lazarenko OP, Wu X, et al. Obesity reduces bone density associated with activation of PPARγ and suppression of Wnt/β-catenin signaling in rapidly growing male rats. PLos ONE. 2010;e13704. This article demonstrates high-fat–induced trabecular bone loss and increased bone marrow adiposity in rats with equal weight gains associated with direct actions of NEFAs on reciprocal regulation of PPAR-γ and Wnt signaling pathways during early development.

  19. • Alvisa-Negrin J, Gonzalez-Reimers E, Santolaria-Fernandez F, et al. Osteopenia in alcoholics: effect of alcohol abstinence. Alcohol Alcoholism. 2009;44:468–75. This article is the first unequivocal demonstration of increased bone resorption in alcoholics.

    PubMed  CAS  Google Scholar 

  20. Dietz-Ruiz A, Garcia-Saura, Garcia-Ruiz PL, et al. Bone mineral density, bone turnover markers and cytokines in alcohol-indcued cirrhosis. Alcohol Alcohol. 2010;45:427–30.

    Google Scholar 

  21. Duggal S, Simpson ME, Keiver K. Effect of chronic ethanol consumption on the response of parathyroid hormone to hypocalcemia in the pregnant rat. Alcohol Clin Exp Res. 2007;31:104–12.

    Article  PubMed  CAS  Google Scholar 

  22. Shankar K, Haley R, Badger TM, et al. Disruption of vitamin D3 homeostasis in rats fed ethanol via total enteral nutrition is the result of induction of CYP24A1. Endocrinology. 2008;149:1748–56.

    Article  PubMed  CAS  Google Scholar 

  23. Howe KS, Iwaniec UT, Turner RT. The effects of low dose parathyroid hormone on lumbar vertebrae in a rat model for chronic alcohol abuse. Osteoporos Int. 2010;(In Press).

  24. Badger TM, Ronis MJJ, Lumpkin CK, et al. Effects of chronic ethanol on growth hormone secretion and hepatic P450 isozymes of the rat. J Pharmacol Exp Ther. 1993;264:438–47.

    PubMed  CAS  Google Scholar 

  25. Turner RT, Rosen CJ, Iwaniec UT. Effects of alcohol on skeletal response to growth hormone in hypophysectomized rats. Bone. 2010;46:806–12.

    Article  PubMed  CAS  Google Scholar 

  26. •• Himes R, Wezeman FH, Callaci JJ. Identification of novel bone-specific molecular targets of binge alcohol and ibandronate by transcriptome analysis. Alc Clin Exp Res. 2008;32:1167–80. This article is the first gene array analysis of alcohol effects on bone and the first to verify that skeletal Wnt signaling is an alcohol target.

    Article  PubMed  CAS  Google Scholar 

  27. • Callaci JJ, Himes R, Lauing K, Roper P. Long term modulations in the vertebral transcriptome of adolescent-stage rats exposed to binge alcohol. Alc Clin Exp Res. 2010;45:332–46. This study demonstrates persistent effects of alcohol on gene expression in bone and identifies clock genes as a novel bone target.

    CAS  Google Scholar 

  28. Perrien DS, Wahl L, Hogue WR, et al. Combined administration of IL-1 and TNF antagonists attenuate ethanol-induced inhibition of fracture healing in the rat. Toxicol Sci. 2004;82:656–60.

    Article  PubMed  CAS  Google Scholar 

  29. Wahl EC, Aronson JA, Liu L, et al. Chronic ethanol exposure inhibits distraction osteogenesis in a mouse model: role of the TNF signaling axis. Toxicol Appl Pharmacol. 2007;220:302–10.

    Article  PubMed  CAS  Google Scholar 

  30. Wahl E, Aronson J, Liu L, et al. Direct bone formation during distraction osteogenesis is not impaired in TNFα receptor deficient mice and recombinant mouse TNFα fails to inhibit bone formation in TNFR1 deficient mice. Bone. 2010;46:410–7.

    Article  PubMed  CAS  Google Scholar 

  31. •• Chen J-R, Lazarenko OP, Blackburn ML, et al. A role for ethanol-induced oxidative stress in controlling lineage commitment of mesenchymal stromal cells through inhibition of Wnt/beta catenin signaling. J Bone Min Res. 2010;25:1117–27. This article describes how alcohol exposure induces oxidative stress in mesenchymal stem cells in vivo and in vitro to inhibit Wnt signaling and osteoblastogenesis and to stimulate adipocyte differentiation.

    Article  PubMed  CAS  Google Scholar 

  32. Chen J-R, Lazarenko OP, Haley RL, et al. Ethanol impairs estrogen receptor signaling and activates senescence pathways in osteoblasts. Protection by estradiol. J Bone Miner Res. 2009;24:221–30.

    Article  PubMed  CAS  Google Scholar 

  33. Wezeman FH, Juknelis D, Himes R, Callaci JJ. Vitamin D and ibandronate prevent cancellous bone loss associated with binge alcohol treatment in male rats. Bone. 2007;41:639–45.

    Article  PubMed  CAS  Google Scholar 

  34. Shankar K, Hidestrand M, Haley R, et al. Different molecular mechanisms underlie ethanol-induced bone loss in cycling and pregnant rats. Endocrinology. 2006;147:166–78.

    Article  PubMed  CAS  Google Scholar 

  35. •• Chen J-R, Badger TM, Nagaragian S, Ronis MJJ. Inhibition of reactive oxygen species generation and downstream activation of the ERK/STAT3/RANKL-signaling cascade to osteoblasts accounts for the protective effects of estradiol on ethanol-induced bone loss. J Pharmacol Exp Ther. 2008;324:50–9. This article is the first study to identify NADPH oxidase-mediated reactive oxygen species activation of an ERK-signaling cascade in the regulation of RANKL expression in osteoblasts.

    Article  PubMed  CAS  Google Scholar 

  36. Chen J-R, Haley RL, Shankar K, et al. Estradiol protects against ethanol-induced bone loss in female rats by inhibiting the up regulation of RANKL. J Pharmacol Exp Ther. 2006;319:1182–90.

    Article  PubMed  CAS  Google Scholar 

  37. Arteel GE. Oxidants and antioxidants in alcoholic liver disease. Gastroenterology. 2003;123:778–90.

    Article  Google Scholar 

  38. Piccoli C, D’Aprile A, Ripoli M, et al. Bone-marrow derived hematopoietic stem/progenitor cells express multiple forms of NADPH oxidase and produce constitutively reactive oxygen species. Biochem Biophys Res Commun. 2007;353:965–72.

    Article  PubMed  CAS  Google Scholar 

  39. Serrander L, Cartier L, Bedard K, et al. NOX4 activity is determined by mRNA levels and reveals a unique pattern of ROS generation. Biochem J. 2007;406:105–14.

    Article  PubMed  CAS  Google Scholar 

  40. •• Chen J-R, Lazarenko OP, Shankar et al. Inhibition of NADPH oxidases prevents chronic ethanol-induced bone loss in female rats. J Pharmacol Exp Ther. 2010;(In Press). This is the first study to identify an essential role for NADPH oxidase-generated oxidative stress in alcohol-induced bone loss in vivo.

  41. Prynne CJ, Mishra GD, O’Connell MA, et al. Fruit and vegetable intakes and bone mineral status: a cross-sectional study in 5 age and sex cohorts. Am J Clin Nutr. 2006;83:1420–8.

    PubMed  CAS  Google Scholar 

  42. Chen Y-M, Ho SC, Woo JLF. Greater fruit and vegetable intake is associated with increased bone mass among postmenopausal Chinese women. Br J Nutr. 2006;96:745–51.

    Article  PubMed  CAS  Google Scholar 

  43. Hooshmand S, Arjmandi BH. Viewpoint: dried plum, an emerging functional food that may effectively improve bone health. Aging Res Revs. 2009;8:122–7.

    Article  CAS  Google Scholar 

  44. • Halloran BP, Wronski TJ, VonHerzen DC, et al. Dietary dried plum increases bone mass in adu lt and aged male mice. J Nutr. 2010;140:1781–7. This study is the first to demonstrate the potential for fruit-derived factors to prevent and reverse aging-associated bone loss.

    Article  PubMed  CAS  Google Scholar 

  45. •• Chen JR, Lazarenko OP, Wu X, et al. Dietary-induced serum phenolic acids promote bone growth via p38 MAPK/β-catenin canonical wnt signaling. J Bone Min Res. 2010;25:2399–412. This is the first study to identify Wnt signaling as the molecular target underlying the bone anabolic effects of berries and to characterize phenolic acid metabolites of polyphenols as the bioactive component.

    Article  PubMed  CAS  Google Scholar 

  46. Zhang Y, Li Q, Wan HY, Helferich WG, Wong MS. Genistein and a soy extract differentially affect three-dimensional bone parameters and bone-specific gene expression in ovariectomized mice. J Nutr. 2009;2230–6.

  47. Chen J-R, Singhal R, Lazarenko OP, et al. Short term effects on bone quality associated with consumption of soy protein isolate and other dietary protein sources in rapidly growing female rats. Exp Biol Med. 2008;233:1348–58.

    Article  CAS  Google Scholar 

  48. Cai DJ, Zhao Y, Glasier J, et al. Comparative effect of soy protein, soy isoflavones and 17β estradiol on bone metabolism in adult ovariectomized rats. J Bone Miner Res. 2005;20:828–39.

    Article  PubMed  CAS  Google Scholar 

  49. • Chen J-R, Lazarenko OP, Blackburn ML, et al. Infant formula promotes bone growth in neonatal piglets by enhancing osteoblastogenesis through bone morphogenic protein signaling. J Nutr. 2009;139:1839–47. This study links bone anabolic effects of soy feeding during early development to stimulation of BMP signaling.

    Article  PubMed  CAS  Google Scholar 

  50. • Trzeciakiewicz A, Habauzit V, Mercier S, et al. Molecular mechanism of hesperetin-7-O-glucuronide, the main circulating metabolite of hesperidin, involved in osteoblast differentiation. J Agr Food Chem. 2010;58:668–75. This study demonstrates activation of BMP signaling in vitro by a conjugated metabolite of an orange juice phytochemical.

    Article  CAS  Google Scholar 

Download references

Acknowledgment

M.J.J. Ronis has received grants from the National Institutes of Health (NIH) (R01 AA18282; PI for R01: M.J.J. Ronis) and Arkansas Children’s Nutrition Center, Federal Center Grant through USDA-ARS (ARS CRIS 6251-51000-005-03 S), and has received support for travel and writing (for NIH R01 AA18282 and ARS CRIS 6251-51000-005-03).

Disclosure

Conflicts of interest: M.J.J. Ronis: has been a consultant for Soy Nutrition Institute and a consultant/grant reviewer for the NIH; K. Mercer: none; J.-R Chen: none.

Author information

Authors and Affiliations

  1. Department of Pharmacology & Toxicology, University of Arkansas for Medical Sciences, Arkansas Children’s Nutrition Center, 15 Children’s Way, Little Rock, AR, 72202, USA

    Martin J. J. Ronis

  2. Arkansas Children’s Nutrition Center, 15 Children’s Way, Little Rock, AR, 72202, USA

    Kelly Mercer

  3. Department of Pediatrics, University of Arkansas for Medical Sciences, Arkansas Children’s Nutrition Center, 15 Children’s Way, Little Rock, AR, 72202, USA

    Jin-Ran Chen

Authors
  1. Martin J. J. Ronis
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kelly Mercer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jin-Ran Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Martin J. J. Ronis.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ronis, M.J.J., Mercer, K. & Chen, JR. Effects of Nutrition and Alcohol Consumption on Bone Loss. Curr Osteoporos Rep 9, 53–59 (2011). https://doi.org/10.1007/s11914-011-0049-0

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11914-011-0049-0

Keywords

Search

Navigation