Administration of alpha-lipoic acid could maintain bone mass and bone strength in senile female rats with alcohol consumption

  • Junfeng Zhan
  • Ya Jiang
  • Nan Zhu
  • Wang Fang
  • Gang WangEmail author
Original Contributions


Previous studies have demonstrated the damaging effect of alcohol (ALH) consumption on bone tissue and bone metabolism. Alpha-lipoic acid (ALA) promotes osteoblast proliferation and inhibits osteoclast proliferation, and positively affects bone regeneration; however, reports about effects of ALA on bone loss for aged female rats with ALH consumption are limited. This study was designed to investigate the impact of treatment with ALA on bone loss for aged female rats with ALH consumption. In this study 30 female Sprague–Dawley rats (22 months old), weighing approximately 520 g, were incorporated. The animals were randomly divided into three groups: group CON, group ALH and group ALH + ALA and received saline, ALH, ALH plus ALA treatment until death at 16 weeks, respectively. The results of maintaining bone mass and bone strength in senile female rats with ALH consumption were evaluated by histology, microcomputerized tomography, gene expression analysis and biomechanical tests. Results from this study indicated that ALH + ALA had stronger effects on the prevention and treatment of osteoporosis in senile female rats with ALH consumption. The ALH + ALA produced stronger effects on the bone volume ratio (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N) and trabecular separation (Tb.Sp), BMD and strength of distal femurs, and regulation of osteogenesis and bone resorption-related gene expression. These results seem to indicate that ALA intervention prevents bone loss in senile female rats with ALH consumption.


Distal femurs Bone mineral density Alpha-lipoic acid Alcohol 

Die Gabe von Alpha-Liponsäure könnte die Knochenmasse und Knochenstärke bei alten weiblichen Ratten mit Alkoholkonsum erhalten


Frühere Studien haben den schädigenden Effekt von Alkohol (ALH) auf Knochengewebe und -stoffwechsel gezeigt. Alpha-Liponsäure (ALA) fördert die Proliferation von Osteoblasten, hemmt die Proliferation von Osteoklasten und hat einen positiven Effekt auf die Knochenregeneration. Berichte über die Auswirkungen von ALA auf den Knochenverlust in alten weiblichen Ratten mit ALH-Konsum sind limitiert. Diese Studie wurde durchgeführt, um den Effekt der ALA-Behandlung auf den Knochenverlust bei alten weiblichen Ratten mit ALH-Konsum zu untersuchen. In diese Studie wurden 30 weibliche Spraque-Dawley-Ratten (22 Monate alt) mit einem Gewicht von ungefähr 520 g eingeschlossen. Die Tiere wurden in drei Gruppen randomisiert: Gruppe CON, Gruppe ALH und Gruppe ALH + ALA, die jeweils Kochsalzlösung, ALH bzw. eine Behandlung mit ALH + ALA bis zum Tod nach 16 Wochen erhielten. Die Ergebnisse für den Erhalt von Knochenmasse und Knochenstärke bei alten weiblichen Ratten mit ALH-Konsum wurden histologisch sowie mittels Mikrocomputertomographie, Genexpressionsanalyse und biomechanischen Tests evaluiert. Die Resultate dieser Studie zeigten, dass ALH + ALA einen stärkeren Effekt auf die Prävention und Behandlung von Osteoporose bei alten weiblichen Ratten mit ALH-Konsum hatte. ALH + ALA hatte einen größeren Effekt auf BV/TV (bone volume ratio), Tb.Th (trabecular thickness), Tb.N (trabecular number) und Tb.Sp (trabecular separation), BMD sowie die Stärke des distalen Femurs, die Osteogeneseregulation und die knochenresorptionsbedinge Genexpression. Diese Ergebnisse scheinen darauf hinzuweisen, dass die Behandlung mit ALA bei alten weiblichen Ratten mit ALH-Konsum einen Knochenverlust verhindert.


Distaler Femur Knochenmineraldichte Alpha-Liponsäure Alkohol 


Compliance with ethical guidelines

Conflict of interest

J. Zhan, Y. Jiang, L. Zhu, W. Fang and G. Wang declare that they have no competing interests.

All procedures performed in studies involving animal testing were in accordance with the ethical standards of the institutional and/or national research committee and with the 1975 Helsinki declaration and its later amendments or comparable ethical standards.


  1. 1.
    Birkhäuser M (2012) Selective estrogen receptor modulators (SERms) for prevention and treatment of postmenopausal osteoporosis. Ther Umsch 69(3):163–172PubMedCrossRefGoogle Scholar
  2. 2.
    Deselm CJ, Zou W, Teitelbaum SL (2012) Halofuginone prevents estrogen-deficient osteoporosis in mice. J Cell Biochem 113(10):3086–3092PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Mithal A, Bansal B, Kyer CS, Ebeling P (2014) The Asia-Pacific regional audit-epidemiology, costs, and burden of osteoporosis in India 2013: a report of International Osteoporosis Foundation. Indian J Endocr Metab 18(4):449CrossRefGoogle Scholar
  4. 4.
    Kutleša Z, Budimir MD (2016) Wine and bone health: a review. J Bone Miner Metab 34(1):11–22PubMedCrossRefGoogle Scholar
  5. 5.
    Nishiguchi S, Shiomi S, Tamori A, Habu D, Takeda T, Tanaka T, Ochi H (2000) Effect of ethanol on bone mineral density of rats evaluated by dual-photon x‑ray absorptiometry. J Bone Miner Metab 18(6):317–320PubMedCrossRefGoogle Scholar
  6. 6.
    Broulík PD, Vondrová J, Růzicka P, Sedlácek R, Zíma T (2010) The effect of chronic alcohol administration on bone mineral content and bone strength in male rats. Physiol Res 59(4):599PubMedGoogle Scholar
  7. 7.
    Sibonga JD, Iwaniec UT, Shogren KL (2007) Effects of parathyroid hormone (1–34) on tibia in an adult rat model for chronic alcohol abuse. Bone 40(4):1013–1020PubMedCrossRefGoogle Scholar
  8. 8.
    Zakaria S, Mat-Husain SZ, Ying-Hwey K et al (2017) Vitamin E improved bone strength and bone minerals in male rats given alcohol. Iran J Basic Med Sci 20(12):1360–1367PubMedPubMedCentralGoogle Scholar
  9. 9.
    Hyunil H, Jong-Ho L, Ha-Neui K, Hyun-Man K, Bok KH, Seungbok L, Hong-Hee K, Hee LZ (2006) alpha-Lipoic acid inhibits inflammatory bone resorption by suppressing prostaglandin E2 synthesis. J Immunol 176(1):111CrossRefGoogle Scholar
  10. 10.
    Dong K, Hao P, Xu S, Liu S, Zhou W, Yue X, Rauschfan X, Liu Z (2017) Alpha-lipoic acid alleviates high-glucose suppressed osteogenic differentiation of MC3T3-E1 cells via antioxidant effect and PI3K/Akt signaling pathway. Cell Physiol Biochem 42(5):1897–1906PubMedCrossRefGoogle Scholar
  11. 11.
    Li X, Ominsky MS, Warmington KS, Morony S, Gong J, Cao J, Gao Y, Shalhoub V, Tipton B, Haldankar R (2010) Sclerostin antibody treatment increases bone formation, bone mass, and bone strength in a rat model of postmenopausal osteoporosis. J Bone Miner Res 24(4):578–588CrossRefGoogle Scholar
  12. 12.
    Tao ZS, Zhou WS, Wu XJ, Zhang X, Wang L, Xie JB, Xu ZJ, Ding GZ, Yang M (2018) Prevention of ovariectomy-induced osteoporosis in rats: comparative study of zoledronic acid, parathyroid hormone (1–34) and strontium ranelate. Z Gerontol Geriatr. PubMedCrossRefGoogle Scholar
  13. 13.
    Chen L, Tao ZS, Chen H, Zhou K, Zhou DS (2017) Combined treatment with alendronate and Drynaria rhizome extracts: effect on fracture healing in osteoporotic rats. Z Gerontol Geriatr. PubMedCrossRefGoogle Scholar
  14. 14.
    Wauquier F, Philippe C, Léotoing L, Mercier S, Davicco MJ, Lebecque P, Guicheux J, Pilet P, Miot-Noirault E, Poitout V, Alquier T, Coxam V, Wittrant Y (2013) The free fatty acid receptor G protein-coupled receptor 40 (GPR40) protects from bone loss through inhibition of osteoclast differentiation. J Biol Chem 288(9):6542–6551PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Kouda K, Iki M, Fujita Y, Tamaki J, Yura A, Kadowaki E, Sato Y, Moon JS, Morikawa M, Tomioka K, Okamoto N, Kurumatani N (2011) Alcohol intake and bone status in elderly Japanese men: baseline data from the Fujiwara-kyo osteoporosis risk in men (FORMEN) study. Bone 49(2):275–280. PubMedCrossRefGoogle Scholar
  16. 16.
    Maurel DB, Boisseau N, Benhamou CL, Jaffre C (2012) Alcohol and bone: review of dose effects and mechanisms. Osteoporos Int 23(1):1–16PubMedCrossRefGoogle Scholar
  17. 17.
    Kelly KN, Kelly C (2013) Pattern and cause of fractures in patients who abuse alcohol: what should we do about it? Postgrad Med J 89(1056):578PubMedCrossRefGoogle Scholar
  18. 18.
    Turner RT (2000) Skeletal response to alcohol. Alcohol Clin Exp Res 24(11):1693–1701PubMedCrossRefGoogle Scholar
  19. 19.
    Jones W, Li X, Qu ZC, Perriott L, Whitesell RR, May JM (2002) Uptake, recycling, and antioxidant actions of α‑lipoic acid in endothelial cells. Free Radic Biol Med 33(1):83–93PubMedCrossRefGoogle Scholar
  20. 20.
    Fu C, Xu D, Wang CY, Jin Y, Liu Q, Meng Q, Liu KX, Sun HJ, Liu MZ (2015) Alpha-lipoic acid promotes osteoblastic formation in H2O2-treated MC3T3-E1 cells and prevents bone loss in ovariectomized rats. J Cell Physiol 230(9):2184–2201PubMedCrossRefGoogle Scholar
  21. 21.
    Roberts JL, Moreau R (2015) Emerging role of alpha-lipoic acid in the prevention and treatment of bone loss. Nutr Rev 73(2):116PubMedCrossRefGoogle Scholar
  22. 22.
    Nurcan YT (2013) The effect of alpha-lipoic acid in ovariectomy and inflammation-mediated osteoporosis on the skeletal status of rat bone. Eur J Pharmacol 718(1):469–474Google Scholar
  23. 23.
    Sibonga JD, Iwaniec UT, Shogren KL, Rosen CJ, Turner RT (2007) Effects of parathyroid hormone (1–34) on tibia in an adult rat model for chronic alcohol abuse. Bone 40(4):1013PubMedCrossRefGoogle Scholar
  24. 24.
    Maurel DB, Jaffre C, Rochefort GY, Aveline PC, Boisseau N, Uzbekov R, Gosset D, Pichon C, Fazzalari NL, Pallu S, Benhamou CL (2011) Low bone accrual is associated with osteocyte apoptosis in alcohol-induced osteopenia. Bone 49(3):543–552PubMedCrossRefGoogle Scholar
  25. 25.
    Chen JR, Lazarenko OP, Shankar K, Blackburn ML, Badger TM, Ronis MJ (2010) A role for ethanol-induced oxidative stress in controlling lineage commitment of mesenchymal stromal cells through inhibition of Wnt/β-catenin signaling. J Bone Miner Res 25(5):1117PubMedCrossRefGoogle Scholar
  26. 26.
    Cui Q, Wang Y, Saleh KJ, Wang GJ, Balian G (2006) Alcohol-induced adipogenesis in a cloned bone-marrow stem cell. J Bone Joint Surg Am 88(3):148–154PubMedGoogle Scholar
  27. 27.
    Bonewald LF, Johnson ML (2008) Osteocytes, mechanosensing and Wnt signaling. Bone 42(4):606–615PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Liu Y, Kou X, Chen C, Yu W, Su Y, Kim Y, Shi S, Liu Y (2016) Chronic high dose alcohol induces osteopenia via activation of mTOR signaling in bone marrow mesenchymal stem cells. Stem Cells 34(8):2157–2168PubMedCrossRefGoogle Scholar
  29. 29.
    González-Reimers E, García-Valdecasas-Campelo E, Santolaria-Fernández F, Sánchez-Pérez MJ, Rodríguez-Rodríguez E, Gómez-Rodríguez MA, Viña-Rodríguez J (2008) Prognostic value of nutritional status in alcoholics, assessed by double-energy x‑ray absorptiometry. Alcohol Alcohol 43(3):314–319PubMedCrossRefGoogle Scholar
  30. 30.
    Kim HJ, Chang EJ, Kim HM, Lee SB, Kim HD, Kim GS, Kim HH (2006) Antioxidant α‑lipoic acid inhibits osteoclast differentiation by reducing nuclear factor-κB DNA binding and prevents in vivo bone resorption induced by receptor activator of nuclear factor-κB ligand and tumor necrosis factor‑α. Free Radic Biol Med 40(9):1483–1493PubMedCrossRefGoogle Scholar

Copyright information

© Springer Medizin Verlag GmbH, ein Teil von Springer Nature 2019

Authors and Affiliations

  • Junfeng Zhan
    • 1
  • Ya Jiang
    • 2
  • Nan Zhu
    • 1
  • Wang Fang
    • 1
  • Gang Wang
    • 3
    Email author
  1. 1.Department of orthopaedics SurgeryThe Second Hospital of Anhui Medical UniversityHefeiChina
  2. 2.Department of OrthopaedicsHefei Third People’s HospitalHefeiChina
  3. 3.Department of orthopaedics SurgeryNanfang Hospital Southern Medical UniversityGuangzhouChina

Personalised recommendations