Current Osteoporosis Reports

, Volume 9, Issue 2, pp 53–59

Effects of Nutrition and Alcohol Consumption on Bone Loss



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.


Oxidative stress Redox Wnt Bone morphogenic protein PPAR-γ Receptor activator of NF-κB ligand Estradiol Mesenchymal stem cell Obesity Nonesterified free fatty acid Berries Fruit Soy Ethanol 


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

  1. 1.
    Reid IR. Fat and bone. Arch Biochem Biophys. 2010;503:20–7.PubMedCrossRefGoogle Scholar
  2. 2.
    Kawai M, Rosen CJ. Adiposity and bone accrual—still an established paradigm? Nat Revs Endocrinol. 2010;6:63–4.CrossRefGoogle Scholar
  3. 3.
    Westendorf JJ, Kahler RA, Schroeder TM. Wnt signaling in osteoblasts and bone diseases. Gene. 2004;341:19–39.PubMedCrossRefGoogle Scholar
  4. 4.
    Canalis E, Economides AN, Gazzerro E. Bone morphogenic proteins, their antagonists, and the skeleton. Endocr Rev. 2003;24:218–35.PubMedCrossRefGoogle Scholar
  5. 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.PubMedCrossRefGoogle Scholar
  6. 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.PubMedCrossRefGoogle Scholar
  7. 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.Google Scholar
  8. 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.PubMedCrossRefGoogle Scholar
  9. 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.PubMedCrossRefGoogle Scholar
  10. 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).Google Scholar
  11. 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.CrossRefGoogle Scholar
  12. 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. PubMedCrossRefGoogle Scholar
  13. 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.PubMedCrossRefGoogle Scholar
  14. 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. Google Scholar
  15. 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.PubMedCrossRefGoogle Scholar
  16. 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.PubMedCrossRefGoogle Scholar
  17. 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.PubMedCrossRefGoogle Scholar
  18. 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. Google Scholar
  19. 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. PubMedGoogle Scholar
  20. 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. 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.PubMedCrossRefGoogle Scholar
  22. 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.PubMedCrossRefGoogle Scholar
  23. 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).Google Scholar
  24. 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.PubMedGoogle Scholar
  25. 25.
    Turner RT, Rosen CJ, Iwaniec UT. Effects of alcohol on skeletal response to growth hormone in hypophysectomized rats. Bone. 2010;46:806–12.PubMedCrossRefGoogle Scholar
  26. 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.PubMedCrossRefGoogle Scholar
  27. 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. Google Scholar
  28. 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.PubMedCrossRefGoogle Scholar
  29. 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.PubMedCrossRefGoogle Scholar
  30. 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.PubMedCrossRefGoogle Scholar
  31. 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. PubMedCrossRefGoogle Scholar
  32. 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.PubMedCrossRefGoogle Scholar
  33. 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.PubMedCrossRefGoogle Scholar
  34. 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.PubMedCrossRefGoogle Scholar
  35. 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. PubMedCrossRefGoogle Scholar
  36. 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.PubMedCrossRefGoogle Scholar
  37. 37.
    Arteel GE. Oxidants and antioxidants in alcoholic liver disease. Gastroenterology. 2003;123:778–90.CrossRefGoogle Scholar
  38. 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.PubMedCrossRefGoogle Scholar
  39. 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.PubMedCrossRefGoogle Scholar
  40. 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. Google Scholar
  41. 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.PubMedGoogle Scholar
  42. 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.PubMedCrossRefGoogle Scholar
  43. 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.CrossRefGoogle Scholar
  44. 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.PubMedCrossRefGoogle Scholar
  45. 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. PubMedCrossRefGoogle Scholar
  46. 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.Google Scholar
  47. 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.CrossRefGoogle Scholar
  48. 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.PubMedCrossRefGoogle Scholar
  49. 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. PubMedCrossRefGoogle Scholar
  50. 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. CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Martin J. J. Ronis
    • 1
  • Kelly Mercer
    • 2
  • Jin-Ran Chen
    • 3
  1. 1.Department of Pharmacology & ToxicologyUniversity of Arkansas for Medical SciencesLittle RockUSA
  2. 2.Arkansas Children’s Nutrition CenterLittle RockUSA
  3. 3.Department of PediatricsUniversity of Arkansas for Medical SciencesLittle RockUSA

Personalised recommendations