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Evidence-Based Complementary and Alternative Medicine
Volume 2012 (2012), Article ID 960742, 9 pages
http://dx.doi.org/10.1155/2012/960742
Research Article

Effects of Tocotrienol and Lovastatin Combination on Osteoblast and Osteoclast Activity in Estrogen-Deficient Osteoporosis

Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur, Malaysia

Received 31 May 2012; Revised 12 July 2012; Accepted 13 July 2012

Academic Editor: Ahmad Nazrun Shuid

Copyright © 2012 Saif Abdul-Majeed et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. C. Jochems, U. Islander, M. Erlandsson, M. Verdrengh, C. Ohlsson, and H. Carlsten, “Osteoporosis in experimental postmenopausal polyarthritis: the relative contributions of estrogen deficiency and inflammation,” Arthritis Research & Therapy, vol. 7, no. 4, pp. R837–843, 2005. View at Scopus
  2. N. E. Cusano, A. G. Costa, B. C. Silva, and J. P. Bilezikian, “Therapy of osteoporosis in men with teriparatid,” Journal of Osteoporosis, vol. 2011, 7 pages, 2011.
  3. R. Hwang, E. J. Lee, M. H. Kim et al., “Calcyclin, a Ca2+ ion-binding protein, contributes to the anabolic effects of simvastatin on bone,” The Journal of Biological Chemistry, vol. 279, no. 20, pp. 21239–21247, 2004. View at Publisher · View at Google Scholar · View at Scopus
  4. J. K. Liao and U. Laufs, “Pleiotropic effects of statins,” Annual Review of Pharmacology and Toxicology, vol. 45, no. 1, pp. 89–118, 2005. View at Publisher · View at Google Scholar · View at Scopus
  5. G. Mundy, R. Garrett, S. Harris et al., “Stimulation of bone formation in vitro and in rodents by statins,” Science, vol. 286, no. 5446, pp. 1946–1949, 1999. View at Publisher · View at Google Scholar · View at Scopus
  6. T. Maeda, A. Matsunuma, T. Kawane, and N. Horiuchi, “Simvastatin promotes osteoblast differentiation and mineralization in MC3T3-E1 cells,” Biochemical and Biophysical Research Communications, vol. 280, no. 3, pp. 874–877, 2001. View at Publisher · View at Google Scholar · View at Scopus
  7. H. Oxlund and T. T. Andreassen, “Simvastatin treatment partially prevents ovariectomy-induced bone loss while increasing cortical bone formation,” Bone, vol. 34, no. 4, pp. 609–618, 2004. View at Publisher · View at Google Scholar · View at Scopus
  8. H. Oxlund, M. Dalstra, and T. T. Andreassen, “Statin given perorally to adult rats increases cancellous bone mass and compressive strength,” Calcified Tissue International, vol. 69, no. 5, pp. 299–304, 2001. View at Scopus
  9. M. L. Ho, Y. H. Chen, H. J. Liao et al., “Simvastatin increases osteoblasts and osteogenic proteins in ovariectomized rats,” European Journal of Clinical Investigation, vol. 39, no. 4, pp. 296–303, 2009. View at Publisher · View at Google Scholar · View at Scopus
  10. F. J. Maritz, M. M. Conradie, P. A. Hulley, R. Gopal, and S. Hough, “Effect of statins on bone mineral density and bone histomorphometry in rodents,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 21, no. 10, pp. 1636–1641, 2001. View at Scopus
  11. C. Song, Z. Guo, Q. Ma et al., “Simvastatin induces osteoblastic differentiation and inhibits adipocytic differentiation in mouse bone marrow stromal cells,” Biochemical and Biophysical Research Communications, vol. 308, no. 3, pp. 458–462, 2003. View at Publisher · View at Google Scholar · View at Scopus
  12. C. J. Edwards, D. J. Hart, and T. D. Spector, “Oral statins and increased bone-mineral density in postmenopausal women,” The Lancet, vol. 355, no. 9222, pp. 2218–2219, 2000. View at Scopus
  13. C. R. Meier, R. G. Schlienger, M. E. Kraenzlin, B. Schlegel, and H. Jick, “HMG-CoA reductase inhibitors and the risk of fractures,” Journal of the American Medical Association, vol. 283, no. 24, pp. 3205–3210, 2000. View at Scopus
  14. D. Bauer, G. Mundy, S. Jamal et al., “Statin use, bone mass and fracture: an analysis of two prospective studies,” Journal of Bone and Mineral Research, vol. 14, supplement 1, p. S179, 1999.
  15. P. S. Wang, D. H. Solomon, H. Mogun, and J. Avorn, “HMG-CoA reductase inhibitors and the risk of hip fractures in elderly patients,” Journal of the American Medical Association, vol. 283, no. 24, pp. 3211–3216, 2000. View at Scopus
  16. Y. S. Chung, M. D. Lee, S. K. Lee, H. M. Kim, and L. A. Fitzpatrick, “HMG-CoA reductase inhibitors increase BMD in type 2 diabetes mellitus patients,” Journal of Clinical Endocrinology & Metabolism, vol. 85, no. 3, pp. 1137–1142, 2000. View at Publisher · View at Google Scholar · View at Scopus
  17. K. A. Chan, S. E. Andrade, M. Boles et al., “Inhibitors of hydroxymethylglutaryl-coenzyme A reductase and risk of fracture among older women,” The Lancet, vol. 355, no. 9222, pp. 2185–2188, 2000. View at Scopus
  18. J. A. Cauley, R. Jackson, M. Pettinger, et al., “Statin use and bone mineral density (BMD)in older women: the Women's Health Initiative Study (WHI-OS),” Journal of Bone and Mineral Research, vol. 152, supplement, p. S155, 2000.
  19. Y. Wada, Y. Nakamura, and H. Koshiyama, “Lack of positive correlation between statin use and bone mineral density in Japanese subjects with type 2 diabetes,” Archives of Internal Medicine, vol. 160, no. 18, pp. 2860–2865, 2000. View at Scopus
  20. T. P. Van Staa, S. Wegman, F. de Vries, B. Leufkens, and C. Cooper, “Use of statins and risk of fractures,” Journal of the American Medical Association, vol. 285, no. 14, pp. 1850–1855, 2001. View at Scopus
  21. A. Z. LaCroix, J. A. Cauley, M. Pettinger et al., “Statin use, clinical fracture, and bone density in postmenopausal women: results from the Women's Health Initiative Observational Study,” Annals of Internal Medicine, vol. 139, no. 2, pp. 97–104, 2003. View at Scopus
  22. A. Z. Lacroix, J. A. Cauley, and R. Jackson, “Does statin use reduce risk of fracture in postmenopausal women? results from the Womens' Health Initiative Observational Study (WHI-OS),” Journal of Bone and Mineral Research, vol. 15, supplement 1, p. S155, 2000.
  23. L. Rejnmark, N. H. Buus, P. Vestergaard et al., “Effects of simvastatin on bone turnover and BMD: a 1-year randomized controlled trial in postmenopausal osteopenic women,” Journal of Bone and Mineral Research, vol. 19, no. 5, pp. 737–744, 2004. View at Publisher · View at Google Scholar · View at Scopus
  24. E. A. Stein, M. Farnier, J. Waldstreicher, M. Mercuri, and Simvastatin/Atorvastatin Study Group, “Effects of statins on biomarkers of bone metabolism: a randomised trial,” Nutrition, Metabolism and Cardiovascular Diseases, vol. 11, no. 2, pp. 84–87, 2001. View at Scopus
  25. J. M. Mostaza, C. De la Piedra, M. D. Curiel, R. Peña, and C. Lahoz, “Pravastatin therapy increases procollagen I N-terminal propeptide (PINP), a marker of bone formation in post-menopausal women,” Clinica Chimica Acta, vol. 308, no. 1-2, pp. 133–137, 2001. View at Publisher · View at Google Scholar · View at Scopus
  26. N. H. Bjarnason, B. J. Riis, and C. Christiansen, “The effect of fluvastatin on parameters of bone remodeling,” Osteoporosis International, vol. 12, no. 5, pp. 380–384, 2001. View at Publisher · View at Google Scholar · View at Scopus
  27. I. Fuentes and C. Aguilera, “Myopathy secondary to the treatment with inhibitors of HMG-CoA reductase,” Medicina Clinica, vol. 111, no. 18, pp. 700–704, 1998. View at Scopus
  28. P. B. Duell, W. E. Connor, and D. R. Illingworth, “Rhabdomyolysis after taking atorvastatin with gemfibrozil,” The American Journal of Cardiology, vol. 81, no. 3, pp. 368–369, 1998. View at Publisher · View at Google Scholar · View at Scopus
  29. R. H. Jacobson, P. Wang, C. J. Glueck, and D. N. Jody, “Myositis and rhabdomyolysis associated with concurrent use of simvastatin and nefazodone,” Journal of the American Medical Association, vol. 277, no. 4, pp. 296–297, 1997. View at Scopus
  30. B. B. Aggarwal, C. Sundaram, S. Prasad, and R. Kannappan, “Tocotrienols, the vitamin E of the 21st century: its potential against cancer and other chronic diseases,” Biochemical Pharmacology, vol. 80, no. 11, pp. 1613–1631, 2010. View at Publisher · View at Google Scholar · View at Scopus
  31. A. S. Nazrun, M. Norazlina, M. Norliza, and S. Ima Nirwana, “Comparison of the effects of tocopherol and tocotrienol on osteoporosis in animal models,” International Journal of Pharmacology, vol. 6, no. 5, pp. 561–568, 2010. View at Scopus
  32. H. Hermizi, O. Faizah, S. Ima-Nirwana, S. Ahmad Nazrun, and M. Norazlina, “Beneficial effects of tocotrienol and tocopherol on bone histomorphometric parameters in Sprague-Dawley male rats after nicotine cessation,” Calcified Tissue International, vol. 84, no. 1, pp. 65–74, 2009. View at Publisher · View at Google Scholar · View at Scopus
  33. A. N. Shuid, Z. Mehat, N. Mohamed, N. Muhammad, and I. N. Soelaiman, “Vitamin E exhibits bone anabolic actions in normal male rats,” Journal of Bone and Mineral Metabolism, vol. 28, no. 2, pp. 149–156, 2010. View at Publisher · View at Google Scholar · View at Scopus
  34. M. Z. Mehat, A. N. Shuid, N. Mohamed, N. Muhammad, and I. N. Soelaiman, “Beneficial effects of vitamin e isomer supplementation on static and dynamic bone histomorphometry parameters in normal male rats,” Journal of Bone and Mineral Metabolism, vol. 28, no. 5, pp. 503–509, 2010. View at Publisher · View at Google Scholar · View at Scopus
  35. T. A. Ahmad, A. S. Nazrun, A. Rashid Nurul Hashimah, et al., “Comparison of the effects of tocotrienol and estrogen on the bone markers and dynamic changes in postmenopausal osteoporosis rat model,” Asian Journal of Animal and Veterinary Advances, vol. 7, no. 3, pp. 225–234, 2012..
  36. P. W. Sylvester, “Synergistic anticancer effects of combined γ-tocotrienol with statin or receptor tyrosine kinase inhibitor treatment,” Genes and Nutrition, vol. 7, no. 1, pp. 63–74, 2011. View at Publisher · View at Google Scholar · View at Scopus
  37. P. W. Sylvester, A. Kaddoumi, S. Nazzal, and K. A. El Sayed, “The value of tocotrienols in the prevention and treatment of cancer,” Journal of the American College of Nutrition, vol. 29, no. 3, supplement, pp. 324S–333S, 2010. View at Scopus
  38. R. A. Parker, B. C. Pearce, R. W. Clark, D. A. Gordon, and J. J. Wright, “Tocotrienols regulate cholesterol production in mammalian cells by post- transcriptional suppression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase,” The Journal of Biological Chemistry, vol. 268, no. 15, pp. 11230–11238, 1993. View at Scopus
  39. B. L. Song and R. A. DeBose-Boyd, “Insig-dependent ubiquitination and degradation of 3-hydroxy-3- methylglutaryl coenzyme A reductase stimulated by δ- and γ-tocotrienols,” The Journal of Biological Chemistry, vol. 281, no. 35, pp. 25054–25061, 2006. View at Publisher · View at Google Scholar · View at Scopus
  40. J. A. McAnally, J. Gupta, S. Sodhani, L. Bravo, and H. Mo, “Tocotrienols potentiate lovastatin-mediated growth suppression in vitro and in vivo,” Experimental Biology and Medicine, vol. 232, no. 4, pp. 523–531, 2007. View at Scopus
  41. B. Tann and A. Mueller, Tocotrienols Vitamin E Beyond Tocopherols, AOCS/CRC, 2008.
  42. S. Ikeda, T. Tohyama, H. Yoshimura, K. Hamamura, K. Abe, and K. Yamashita, “Dietary α-tocopherol decreases α-tocotrienol but not γ-tocotrienol concentration in rats,” Journal of Nutrition, vol. 133, no. 2, pp. 428–434, 2003. View at Scopus
  43. A. Shibata, K. Nakagawa, P. Sookwong, T. Tsuduki, A. Asai, and T. Miyazawa, “α-Tocopherol attenuates the cytotoxic effect of δ-tocotrienol in human colorectal adenocarcinoma cells,” Biochemical and Biophysical Research Communications, vol. 397, no. 2, pp. 214–219, 2010. View at Publisher · View at Google Scholar · View at Scopus
  44. H. T. Khor and T. T. Ng, “Effects of administration of α-tocopherol and tocotrienols on serum lipids and liver HMG CoA reductase activity,” International Journal of Food Sciences and Nutrition, vol. 51, supplement, pp. S3–S11, 2000. View at Scopus
  45. S. C. Chai, C. I. Wei, K. Brummel-Smith, and B. H. Arjmandi, “The role of vitamin E in reversing bone loss,” Aging—Clinical and Experimental Research, vol. 20, no. 6, pp. 521–527, 2008. View at Scopus
  46. F. Deyhim, C. Garcia, A. Villareal et al., “Vitamin E does not support bone quality in orchidectomized rats,” Current Issues in Food and Nutrition, vol. 3, no. 4, pp. 300–303, 2007. View at Scopus
  47. R. T. Turner, A. Maran, S. Lotinun et al., “Animal models for osteoporosis,” Reviews in Endocrine & Metabolic Disorders, vol. 2, no. 1, pp. 117–127, 2001. View at Publisher · View at Google Scholar · View at Scopus
  48. S. M. Weisman and V. Matkovic, “Potential use of biochemical markers of bone turnoverfor assessing the effect of calcium supplementation and predicting fracture risk,” Clinical Therapeutics, vol. 27, no. 3, pp. 299–308, 2005. View at Publisher · View at Google Scholar · View at Scopus
  49. J. E. Compston and P. I. Croucher, “Histomorphometric assessment of trabecular bone remodelling in osteoporosis,” Bone and Mineral, vol. 14, no. 2, pp. 91–102, 1991. View at Publisher · View at Google Scholar · View at Scopus
  50. E. Dogan and C. Posaci, “Monitoring hormone replacement therapy by biochemical markers of bone metabolism in menopausal women,” Postgraduate Medical Journal, vol. 78, no. 926, pp. 727–731, 2002. View at Publisher · View at Google Scholar · View at Scopus
  51. S. D. Vasikaran, “Utility of biochemical markers of bone turnover and bone mineral density in management of osteoporosis,” Critical Reviews in Clinical Laboratory Sciences, vol. 45, no. 2, pp. 221–258, 2008. View at Publisher · View at Google Scholar · View at Scopus
  52. S. Ima-Nirwana, M. Norazlina, and B. A. K. Khalid, “Pattern of bone mineral density in growing male and female rats after gonadectomy,” Journal of the Asean Federation of Endocrine Society, vol. 16, pp. 21–36, 1998.
  53. A. M. Parfitt, M. K. Drezner, F. H. Glorieux et al., “Bone histomorphometry: standardization of nomenclature, symbols, and units: report of the asbmr histomorphometry nomenclature committee,” Journal of Bone and Mineral Research, vol. 2, no. 6, pp. 595–610, 1987. View at Scopus
  54. B. Clarke, “Normal bone anatomy and physiology,” Clinical Journal of the American Society of Nephrology, vol. 3, supplement 3, pp. S131–S139, 2008. View at Publisher · View at Google Scholar · View at Scopus
  55. W. A. Grasser, A. P. Baumann, S. F. Petras et al., “Regulation of osteoclast differentiation by statins,” Journal of Musculoskeletal Neuronal Interactions, vol. 3, no. 1, pp. 53–62, 2003. View at Scopus
  56. A. Dudakovic, A. J. Wiemer, K. M. Lamb, L. A. Vonnahme, S. E. Dietz, and R. J. Hohl, “Inhibition of geranylgeranyl diphosphate synthase induces apoptosis through multiple mechanisms and displays synergy with inhibition of other isoprenoid biosynthetic enzymes,” Journal of Pharmacology and Experimental Therapeutics, vol. 324, no. 3, pp. 1028–1036, 2008. View at Publisher · View at Google Scholar · View at Scopus
  57. U. N. Das, “Nitric oxide as the mediator of the antiosteoporotic actions of estrogen, statins, and essential fatty acids,” Experimental Biology and Medicine, vol. 227, no. 2, pp. 88–93, 2002. View at Scopus
  58. I. R. Garrett, G. Gutierrez, and G. R. Mundy, “Statins and bone formation,” Current Pharmaceutical Design, vol. 7, no. 8, pp. 715–736, 2001. View at Publisher · View at Google Scholar · View at Scopus
  59. I. R. Garrett and G. R. Mundy, “The role of statins as potential targets for bone formation,” Arthritis Research and Therapy, vol. 4, no. 4, pp. 237–240, 2002. View at Publisher · View at Google Scholar · View at Scopus
  60. P. Y. Chen, J. S. Sun, Y. H. Tsuang, M. H. Chen, P. W. Weng, and F. H. Lin, “Simvastatin promotes osteoblast viability and differentiation via Ras/Smad/Erk/BMP-2 signaling pathway,” Nutrition Research, vol. 30, no. 3, pp. 191–199, 2010. View at Publisher · View at Google Scholar · View at Scopus
  61. J. L. Goldstein, R. A. DeBose-Boyd, and M. S. Brown, “Protein sensors for membrane sterols,” Cell, vol. 124, no. 1, pp. 35–46, 2006. View at Publisher · View at Google Scholar · View at Scopus
  62. S. Ima-Nirwana and S. Suhaniza, “Effects of tocopherols and tocotrienols on body composition and bone calcium content in adrenalectomized rats replaced with dexamethasone,” Journal of Medicinal Food, vol. 7, no. 1, pp. 45–51, 2004. View at Publisher · View at Google Scholar · View at Scopus
  63. N. S. Ahmad, B. A. K. Khalid, D. A. Luke, and S. Ima-Nirwana, “Tocotrienol offers better protection than tocopherol from free radical-induced damage of rat bone,” Clinical and Experimental Pharmacology and Physiology, vol. 32, no. 9, pp. 761–770, 2005. View at Publisher · View at Google Scholar · View at Scopus
  64. S. Ima-Nirwana, A. Kiftiah, T. Sariza, M. T. Gapor, and B. A. K. Khalid, “Palm vitamin E improves bone metabolism and survival rate in thyrotoxic rats,” General Pharmacology, vol. 32, no. 5, pp. 621–626, 1999. View at Publisher · View at Google Scholar · View at Scopus
  65. M. Norazlina, P. L. Lee, H. I. Lukman, A. S. Nazrun, and S. Ima-Nirwana, “Effects of vitamin E supplementation on bone metabolism in nicotine-treated rats,” Singapore Medical Journal, vol. 48, no. 3, pp. 195–199, 2007. View at Scopus
  66. M. Norazlina, H. Hermizi, O. Faizah, and S. Ima-Nirwana, “Vitamin E reversed nicotine-induced toxic effects on bone biochemical markers in male rats,” Archives of Medical Science, vol. 6, no. 4, pp. 505–512, 2010. View at Publisher · View at Google Scholar · View at Scopus
  67. S. Ima-Nirwana, M. Norazlina, and B. A. K. Khalid, “Palm vitamin E prevents osteoporosis in orchidectomized growing male rats,” Natural Product Sciences, vol. 6, no. 4, pp. 155–160, 2000. View at Scopus
  68. S. Ima-Nirwana and H. Fakhrurazi, “Palm vitamin E protects bone against dexamethasone-induced osteoporosis in male rats,” Medical Journal of Malaysia, vol. 57, no. 2, pp. 136–144, 2002.
  69. M. Norazlina, S. Ima-Nirwana, M. T. Gapor, and B. A. K. Khalid, “Palm vitamin E is comparable to α-tocopherol in maintaining bone mineral density in ovariectomised female rats,” Experimental and Clinical Endocrinology and Diabetes, vol. 108, no. 4, pp. 305–310, 2000. View at Publisher · View at Google Scholar · View at Scopus
  70. S. Ima-Nirwan, Y. Nurshazwan, A. S. Nazrun, M. Norliza, and M. Norazlina, “Subacute and subchronic toxicity studies of palm vitamin E in mice,” Journal of Pharmacology and Toxicology, vol. 6, no. 2, pp. 166–173, 2011.
  71. B. A. Hamelin and J. Turgeon, “Hydrophilicity/lipophilicity: relevance for the pharmacology and clinical effects of HMG-CoA reductase inhibitors,” Trends in Pharmacological Sciences, vol. 19, no. 1, pp. 26–37, 1998. View at Publisher · View at Google Scholar · View at Scopus
  72. G. D. Braatvedt, W. Bagg, G. Gamble, J. Davidson, and I. R. Reid, “The effect of atorvastatin on markers of bone turnover in patients with type 2 diabetes,” Bone, vol. 35, no. 3, pp. 766–770, 2004. View at Publisher · View at Google Scholar · View at Scopus
  73. D. C. Bauer, G. R. Mundy, S. A. Jamal et al., “Use of statins and fracture: results of 4 prospective studies and cumulative metaanalysis of observational studies and controlled trials,” Archives of Internal Medicine, vol. 164, no. 2, pp. 146–152, 2004. View at Publisher · View at Google Scholar · View at Scopus
  74. W. Yao, R. Farmer, R. Cooper et al., “Simvastatin did not prevent nor restore ovariectomy-induced bone loss in adult rats,” Journal of Musculoskeletal Neuronal Interactions, vol. 6, no. 3, pp. 277–283, 2006. View at Scopus