Effect of Quercetin on Bone Mineral Status and Markers of Bone Turnover in Retinoic Acid-Induced Osteoporosis

Open access

Abstract

Retinoic acid-induced osteoporosis (RBM) is one of the most common causes of secondary osteoporosis. This study tested the anti-osteoporetic effect of quercetin in RBM-induced bone loss model (RBM). After 14-day supplementation of 13cRA to induce RBM, rats were administered with quercetin (100 mg/kg) or alendronate (40 mg/kg). We analysed changes in body and uterine weight of animals, femoral geometric characteristics, calcium and phosphorus content, bone weight index, bone hystology, bone mineral density (BMD), markers of bone turnover, lipid peroxidation, glutathione levels and SOD, CAT activity of liver, kidney spleen, and ovary as well as biochemical and haematological variables. In comparison to the control RBM rats, the treatment with quercetin increased bone weight index, BMD, osteocalcin level, femoral geometric characteristics, calcium and phosphorus content in the 13cRA-induced bone loss model. Histological results showed its protective action through promotion of bone formation. According to the results, quercetin could be an effective substitution for alendronate in 13cRA-induced osteoporosis. Good therapeutic potential of quercetin on rat skeletal system is based partly on its antioxidant capacity and estrogenic activity.

If the inline PDF is not rendering correctly, you can download the PDF file here.

  • 1. Ali A.A. Effect of alendronate sodium (Fosamax) on bone of adult male Sprague dawley rats under glucocorticoids therapy histological and histochemical study. Egypt. J. Histol. 2006 29 1 61-72.

  • 2. Bitto A. Burnett B.P. Polito F. Levy R.M. Marini H. Di Stefano V. Irrera N. Armbruster M.A. Minutoli L. Altavilla D. Squadrito F. Genistein aglycone reverses glucocorticoid-induced osteoporosis and increases bone breaking strength in rats: a comparative study with alendronate. Br. J. Pharmacol. 2009 156 1287-1295.

  • 3. Chavassieux P.M. Arlot M.E. Reda C. Wei L. Yates A.J. Meunier P.J. Histomorphometric assessment of the long-term effects of alendronate on bone quality and remodeling in patients with osteoporosis. J. Clin. Invest. 1997 100 1475-1480.

  • 4. Chiang C.H. Huang C.C. Chan W.L. Huang P.H. Chen T.J. Chung C.M. Lin S.J. Chen J.W. Leu H.B. Oral alendronate use and risk of cancer in postmenopausal women with osteoporosis: A nationwide study. J. Bone. Miner. Res. 2012 27 1951-1958.

  • 5. Conwell L.S. Chang A.B. Bisphosphonates for osteoporosis in people with cystic fi brosis. Cochrane Database. Syst. Rev. 2012 doi:

    • Crossref
    • Export Citation
  • 6. Coskun O. Kanter M. Korkmaz A. Oter S. Quercetin a flavonoid antioxidant prevents and protects streptozotocin-induced oxidative stress and beta-cell damage in rat pancreas. Pharmacol. Res. 2005 51 117-123.

  • 7. Coxam V. Phyto-oestrogens and bone health. Proc. Nutr. Soc. 2008 67 184-95.

  • 8. Fahmy S.R. Soliman A.M. Oxidative stress as a risk factor of osteoporotic by vitamin A in rats. Aust. J. Basic. Appl. Sci. 2009 3 1559-1568.

  • 9. Henning P. Conaway H.H. Lerner U.H. Retinoid receptors in bone and their role in bone remodeling. Front Endocrinol (Lausanne). 2015 6:31. doi:

    • Crossref
    • Export Citation
  • 10. Hotchkiss C.E. Latendresse J. Ferguson S.A. Oral treatment with retinoic acid decreases bone mass in rats. Comp. Med. 2006 56 502-511.

  • 11. Hozayen W.G. El-Desouky M.A. Soliman H.A. Ahmed R.R. Khaliefa A.K. Antiosteoporotic effect of Petroselinum crispum Ocimum basilicum and Cichorium intybus L. in glucocorticoidinduced osteoporosis in rats. BMC Complement Altern. Med. 2016 Jun 2; 16 165 doi:

    • Crossref
    • Export Citation
  • 12. Huuskonen J. Arnala I. Olkkonen H. Alhava E. Alendronate infl uences bending force of femoral diaphysis after orchidectomy in rats. Ann. Chir. Gynaecol. 2001 90 109-114.

  • 13. Inoue J. Choi J.M. Yoshidomi T. Yashiro T. Sato R. Quercetin enhances VDR activity leading to stimulation of its target gene expression in Caco-2 cells. Nutr. Sci. Vitaminol. (Tokyo). 2010 56 326-330.

  • 14. Iwaniec U.T. Turner R.T. Smith B.J. Stoecker B.J. Rust A. Zhang B. Vasu V.T. Gohil K. Cross C.E. Traber M.G. Evaluation of long-term vitamin E insuffi ciency or excess on bone mass density and microarchitecture in rodents. Free. Radic. Biol. Med. 2013 65 1209-1214.

  • 15. Johansson S. Melhus H. Vitamin A antagonizes calcium response to vitamin D in man. J. Bone. Miner. Res. 2001 16 1899-1905.

  • 16. Johnell O. Kanis J.A. An estimate of the worldwide prevalence and disability associated with osteoporotic fractures. Osteoporos. Int. 2006 17 1726-1733.

  • 17. Kneissel M. Studer A. Cortesi R. Susa M. Retinoid-induced bone thinning is caused by subperiosteal osteoclast activity in adult rodents. Bone 2005 36 202-214.

  • 18. Knežević A.H. Dikić D. Lisičić D. Kopjar N. Oršolić N. Karabeg S. Benković V. Synergistic effects of irinotecan and fl avonoids on Ehrlich ascites tumour-bearing mice. Basic. Clin. Pharmacol. Toxicol. 2011 109 343-349.

  • 19. Liang W. Luo Z. Ge S. Du J. Yang M. Yan M. Ye Z. Luo Z. Oral administration of quercetin inhibits bone loss in rat model of diabetic osteopenia. Eur. J. Pharmacol. 2011 670 317-324.

  • 20. Liu R.H. Kang X. Xu L.P. Nian H.L. Yang X.W. Shi H.T. Wang X.J. Effects of the combined extracts of Herba epimedii and Fructus ligustri Lucidi on bone mineral content and bone turnover in osteoporotic rats. BMC Complement Altern. Med. 2015 Apr 9 15 112 doi:

    • Crossref
    • Export Citation
  • 21. Mackinnon E.S. Rao A.V. Josse R.G. Rao L.G. Supplementation with the antioxidant lycopene signifi cantly decreases oxidative stress parameters and the bone resorption marker N-telopeptide of type I collagen in postmenopausal women. Osteoporos. Int. 2011 22 1091-1101.

  • 22. Manolagas S.C. Birth and death of bone cells: Basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis. Endocr. Rev. 2009 21 115-137.

  • 23. Mukherjee M. Das A.S. Mitra S. Mitra C. Prevention of bone loss by oil extract of garlic (Allium sativum Linn.) in an ovariectomized rat model of osteoporosis. Phytother. Res. 2004 18 389-394.

  • 24. Muthusami S. Ramachandran I. Muthusami B. Vasudevan G. Prabhu V. Subramaniam V. Jagadeesan A. Narasimha S. Ovariectomy induces oxidative stress and impairs bone antioxidant system in adult rats. Clinica. Chimica. Acta 2005 360 81-86.

  • 25. Nowak B. Matuszewska A. Filipiak J. Nikodem A. Merwid-Ląd A. Pieśniewska M. Kwiatkowska J. Grotthus B. Szeląg A..The negative impact of selective activation of retinoic acid receptors on bone metabolism and bone mechanical properties in rats. Adv. Clin. Exp. Med. 2016 25 213-218.

  • 26. Oršolić N. Benković V. Lisičić D. Dikić D. Erhardt J. Knežević A.H. Protective effects of propolis and related polyphenolic/fl avonoid compounds against toxicity induced by irinotecan. Med. Oncol. 2010 27 1346-1358.

  • 27. Oršolić N. Car N. Quercetin and hyperthermia modulate cisplatin- induced DNA damage in tumor and normal tissues in vivo. Tumour Biol. 2014 35 6445-6454.

  • 28. Oršolić N. Gajski G. Garaj-Vrhovac V. Dikić D. Prskalo Z.Š. Sirovina D. DNA-protective effects of quercetin or naringenin in alloxan-induced diabetic mice. Eur. J. Pharmacol. 2011 656 110-118.

  • 29. Oršolić N. Goluža E. Đikić D. Lisičić D. Sašilo K. Rođak E. Jeleč Z. Lazarus M.V. Orct T. Role of flavonoids on oxidative stress and mineral contents in the retinoic acid-induced bone loss model of rat. Eur. J. Nutr. 2014 53 1217-1227.

  • 30. Oršolić N. Kunštić M. Kukolj M. Gračan R. Nemrava J. Oxidative stress polarization of macrophages and tumour angiogenesis: Effi cacy of caffeic acid. Chem. Biol. Interact. 2016 256 111-124.

  • 31. Peng X. Jianfeng Y. Weizhang J. Qiankun C. Xio G. The effect of osteoporotic model rats induced by retinoic acid. Chinese Int. J. Traumatol. 2005 4 1-6.

  • 32. Perazzella M.A. Markowitz G.S. Bisphosphonate nephrotoxicity. Kidney Int. 2008 74 1385-93.

  • 33. Pitts C.J. Kearns A.E. Update on medications with adverse skeletal effects. Mayo Clin. Proc. 2011 86 338-343.

  • 34. Prouillet C. Mazière J.C. Mazière C. Wattel A. Brazier M. Kamel S. Stimulatory effect of naturally occurring flavonols quercetin and kaempferol on alkaline phosphatase activity in MG-63 human osteoblasts through ERK and estrogen receptor pathway. Biochem. Pharmacol. 2004 67 1307-1313.

  • 35. Rohde C.M. Manatt M. Clagett-Dame U. DeLuca H.F. Vitamin A antagonizes the action of vitamin D in rats. J. Nutr. 1999 129 2246-2250.

  • 36. Sheweita S.A. Khoshhal K.I. Calcium metabolism and oxidative stress in bone fractures: role of antioxidants. Curr. Drug. Metab. 2007 8 519-525.

  • 37. Togari A. Kondo M. Arai M. Matsumoto S. Effects of retinoic acid on bone formation and resorption in cultured mouse calvaria. Gen. Pharmacol. 1991 22 287-292.

  • 38. Tsuji M. Yamamoto H. Sato T. Mizuha Y. Kawai Y. Taketani Y. Kato S. Terao J. Inakuma T. Takeda E. Dietary quercetin inhibits bone loss without effect on the uterus in ovariectomized mice. J. Bone. Miner. Metab. 2009 27 673-681.

  • 39. Walker-Bone K. Recognizing and treating secondary osteoporosis. Nat. Rev. Rheumatol. 2012 8 480-492.

  • 40. Wattel A. Kamel S. Prouillet C. Petit J.P. Lorget F. Offord E. Brazier M. Flavonoid quercetin decreases osteoclastic differentiation induced by RANKL via a mechanism involving NF kappa B and AP-1. J. Cell Biochem. 2004 92 285-295.

  • 41. Wei M. Yang Z. Li P. Zhang Y. Sse W.C. Anti -osteoporosis activity of naringin in the retinoic acid-induced osteoporosis model. Am. J. Chin. Med. 2007 35 663-667.

  • 42. Woo J.T. Nakagawa H. Notoya M. Yonezawa T. Udagawa N. Lee I.S. Ohnishi M. Hagiwara H. Nagai K. Quercetin supresses bone resorption by inhibiting the differentiation and activation of osteoclasts. Biol. Pharm. Bull. 2004 27 504-509.

  • 43. Xu Y.X. Wu C.L. Wu Y. Tong P.J. Jin H.T. Yu N.Z. Xiao L.W. Epimedium-derived flavonoids modulate the balance between osteogenic differentiation and adipogenic differentiation in bone marrow stromal cells of ovariectomized rats via Wnt/β-catenin signal pathway activation. Chin. J. Integr. Med. 2012 18 909-917.

  • 44. Yang J. Wu N. Peng J. Yang X. Guo J. Yin S. Wang J. Prevention of retinoic acid-induced osteoporosis in mice by isofl avoneenriched soy protein. J Sci Food Agric. 2016 96 331-338.

  • 45. Zhao S. Niu .F Xu C.Y. Liu Y. Ye L. Bi G.B. Chen L. Tian G. Nie T.H. Diosgenin prevents bone loss on retinoic acid-induced osteoporosis in rats. Irish J. Med. Sci. 2016 185 581-587.

Search
Journal information
Impact Factor


IMPACT FACTOR 2017: 1.697
5-year IMPACT FACTOR: 1.760



CiteScore 2018: 1.92

SCImago Journal Rank (SJR) 2018: 0.621
Source Normalized Impact per Paper (SNIP) 2018: 0.908

Cited By
Metrics
All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 671 397 13
PDF Downloads 423 260 6