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Osteoporosis International

Erschienen in:

12.01.2018 | Original Article

Tocotrienol supplementation suppressed bone resorption and oxidative stress in postmenopausal osteopenic women: a 12-week randomized double-blinded placebo-controlled trial

verfasst von: C.-L. Shen, S. Yang, M. D. Tomison, A. W. Romero, C. K. Felton, H. Mo

Erschienen in: Osteoporosis International | Ausgabe 4/2018

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Abstract

Summary

Tocotrienols have shown bone-protective effect in animals. This study showed that a 12-week tocotrienol supplementation decreased concentrations of bone resorption biomarker and bone remodeling regulators via suppressing oxidative stress in postmenopausal osteopenic women.

Introduction

Tocotrienols (TT) have been shown to benefit bone health in ovariectomized animals, a model of postmenopausal women. The purpose of this study was to evaluate the effect of 12-week TT supplementation on bone markers (serum bone-specific alkaline phosphatase (BALP), urine N-terminal telopeptide (NTX), serum soluble receptor activator of nuclear factor-kappaB ligand (sRANKL), and serum osteoprotegerin (OPG)), urine calcium, and an oxidative stress biomarker (8-hydroxy-2′-deoxyguanosine (8-OHdG)) in postmenopausal women with osteopenia.

Methods

Eighty-nine postmenopausal osteopenic women (59.7 ± 6.8 year, BMI 28.7 ± 5.7 kg/m²) were randomly assigned to three groups: (1) placebo (430 mg olive oil/day), (2) low TT (430 mg TT/day, 70% purity), and (3) high TT (860 mg TT/day, 70% purity). TT, an extract from annatto seed with 70% purity, consisted of 90% delta-TT and 10% gamma-TT. Overnight fasting blood and urine samples were collected at baseline, 6, and 12 weeks for biomarker analyses. Eighty-seven subjects completed the 12-week study.

Results

Relative to the placebo group, there were marginal decreases in serum BALP level in the TT-supplemented groups over the 12-week study period. Significant decreases in urine NTX levels, serum sRANKL, sRANKL/OPG ratio, and urine 8-OHdG concentrations and a significant increase in BALP/NTX ratio due to TT supplementation were observed. TT supplementation did not affect serum OPG concentrations or urine calcium levels throughout the study period. There were no significant differences in NTX level, BALP/NTX ratio, sRANKL level, and sRANKL/OPG ratio between low TT and high TT groups.

Conclusions

Twelve-week annatto-extracted TT supplementation decreased bone resorption and improved bone turnover rate via suppressing bone remodeling regulators in postmenopausal women with osteopenia. Such osteoprotective TT’s effects may be, in part, mediated by an inhibition of oxidative stress.

Trial registration

ClinicalTrials.gov identifier: NCT02058420. Title: Tocotrienols and bone health of postmenopausal women.

Wauquier F, Leotoing L, Coxam V, Guicheux J, Wittrant Y (2009) Oxidative stress in bone remodelling and disease. Trends Mol Med 15(10):468–477. https://doi.org/10.1016/j.molmed.2009.08.004 CrossRefPubMed

NIH (2001) Consensus Development Panel on Osteoporosis Prevention, Diagnosis, and Therapy. Osteoporosis prevention, diagnosis, and therapy. JAMA 285(6):785–795CrossRef

National Osteoporosis Foundation. American’s bone health: the state of osteoporosis and low bone mass in our nation. Washington, DC: National Osteoporosis Foundation, 2002;1–55

Rizzoli R, Reginster JY (2011) Adverse drug reactions to osteoporosis treatments. Expert Rev Clin Pharmacol 4(5):593–604. https://doi.org/10.1586/ecp.11.42 CrossRefPubMed

Shahidi F, de Camargo AC (2016) Tocopherols and tocotrienols in common and emerging dietary sources: occurrence, applications, and health benefits. Int J Mol Sci 17(10):E1745CrossRefPubMed

Nizar AM, Nazrun AS, Norazlina M, Norliza M, Ima Nirwana S (2011) Low dose of tocotrienols protects osteoblasts against oxidative stress. Clin Ter 162(6):533–538PubMed

Ha H, Lee JH, Kim HN, Lee ZH (2011) Alpha-tocotrienol inhibits osteoclastic bone resorption by suppressing RANKL expression and signaling and bone resorbing activity. Biochem Biophys Res Commun 406(4):546–551. https://doi.org/10.1016/j.bbrc.2011.02.085 CrossRefPubMed

Brooks R, Kalia P, Ireland DC, Beeton C, Rushton N (2011) Direct inhibition of osteoclast formation and activity by the vitamin E isomer gamma-tocotrienol. Int J Vitam Nutr Res 81(6):358–367. https://doi.org/10.1024/0300-9831/a000087 CrossRefPubMed

Gürkan L, Ekeland A, Gautvik KM, Langeland N, Rønningen H, Solheim LF (1986) Bone changes after castration in rats. A model for osteoporosis. Acta Orthop Scand 57(1):67–70. https://doi.org/10.3109/17453678608993219 CrossRefPubMed

10.

Soelaiman IN, Ming W, Abu Bakar R, Hashnan NA, Mohd Ali H, Mohamed N, Muhammad N, Shuid AN (2012) Palm tocotrienol supplementation enhanced bone formation in oestrogen-deficient rats. Int J Endocrinol 2012:532862CrossRefPubMedPubMedCentral

11.

Deng L, Ding Y, Peng Y, Wu Y, Fan J, Li W, Yang R, Yang M, Fu Q (2014) γ-Tocotrienol protects against ovariectomy-induced bone loss via mevalonate pathway as HMG-CoA reductase inhibitor. Bone 67:200–207. https://doi.org/10.1016/j.bone.2014.07.006 CrossRefPubMed

12.

Abdul-Majeed S, Mohamed N, Soelaiman IN (2012) Effects of tocotrienol and lovastatin combination on osteoblast and osteoclast activity in estrogen-deficient osteoporosis. Evid Based Complement Alternat Med 2012:960742CrossRefPubMedPubMedCentral

13.

Aktifanus AT, Shuid AN, Rashid NHA, Ling TH, Loong CY, Saat NM, Muhammad N, Mohamed N, Soelaiman IN (2012) Comparison of the effects of tocotrienol and estrogen on the bone markers and dynamic changes in postmenopausal osteoporosis rat model. Asian J Anim Vet Adv 7:225–234CrossRef

14.

Shibata A, Nakagawa K, Sookwong P, Tsuduki T, Asai A, Miyazawa T (2010) α-Tocopherol attenuates the cytotoxic effect of δ-tocotrienol in human colorectal adenocarcinoma cells. Biochem Biophys Res Commun 397(2):214–219. https://doi.org/10.1016/j.bbrc.2010.05.087 CrossRefPubMed

15.

Shen CL, Klein A, Chin KY, Mo H, Tsai P, Yang RS, Chyu MC, Ima-Nirwana S (2017) Tocotrienols for bone health: a translational approach. Ann N Y Acad Sci 1401:150–165.

16.

Reagan-Shaw S, Nihal M, Ahmad N (2008) Dose translation from animal to human studies revisited. FASEB J 22(3):659–661. https://doi.org/10.1096/fj.07-9574LSF CrossRefPubMed

17.

Kruger MC, Ha PC, Todd JM, Kuhn-Sherlock B, Schollum LM, Ma J, Qin G, Lau E (2012) High-calcium, vitamin D fortified milk is effective in improving bone turnover markers and vitamin D status in healthy postmenopausal Chinese women. Eur J Clin Nutr 66(7):856–861. https://doi.org/10.1038/ejcn.2012.54 CrossRefPubMed

18.

Li Z, Karp H, Zerlin A, Lee TY, Carpenter C, Heber D (2010) Absorption of silicon from artesian aquifer water and its impact on bone health in postmenopausal women: a 12 week pilot study. Nutr J 9(1):44. https://doi.org/10.1186/1475-2891-9-44 CrossRefPubMedPubMedCentral

19.

Shen CL, Mo H, Yang S, Wang S, Felton CK, Tomison MD, Soelaiman IN (2016) Safety and efficacy of tocotrienol supplementation for bone health in postmenopausal women: protocol for a dose-response double-blinded placebo-controlled randomised trial. BMJ Open 6(12):e012572. https://doi.org/10.1136/bmjopen-2016-012572 CrossRefPubMedPubMedCentral

20.

Iwamoto J, Takada T (2015) Effect of minodronate on the speed of sound of the calcaneus in postmenopausal women with an increased risk of fractures: a clinical practice-based observational study. J Chin Med Assoc 78(10):591–596. https://doi.org/10.1016/j.jcma.2015.06.010 CrossRefPubMed

21.

Naylor KE, Jacques RM, Peel NF, Gossiel F, Eastell R (2016) Response of bone turnover markers to raloxifene treatment in postmenopausal women with osteopenia. Osteoporos Int 27(8):2585–2592. https://doi.org/10.1007/s00198-016-3573-z CrossRefPubMed

22.

Norazlina M, Ima-Nirwana S, Gapor MT, Khalid BA (2000) Palm vitamin E is comparable to alpha-tocopherol in maintaining bone mineral density in ovariectomised female rats. Exp Clin Endocrinol Diabetes 108(04):305–310. https://doi.org/10.1055/s-2000-7758 CrossRefPubMed

23.

Zittermann A, Geppert J, Baier S, Zehn N, Gouni-Berthold I, Berthold HK, Reinsberg J, Stehle P (2004) Short-term effects of high soy supplementation on sex hormones, bone markers, and lipid parameters in young female adults. Eur J Nutr 43(2):100–108. https://doi.org/10.1007/s00394-004-0447-5 CrossRefPubMed

24.

Shen CL, Chyu MC, Yeh JK, Zhang Y, Pence BC, Felton CK, Brismée JM, Arjmandi BH, Doctolero S, Wang JS (2012) Effect of green tea and Tai Chi on bone health in postmenopausal osteopenic women: a 6-month randomized placebo-controlled trial. Osteoporos Int 23(5):1541–1552. https://doi.org/10.1007/s00198-011-1731-x CrossRefPubMed

25.

Clarke BL, Khosla S (2010) Physiology of bone loss. Radiol Clin N Am 48(3):483–495. https://doi.org/10.1016/j.rcl.2010.02.014 CrossRefPubMedPubMedCentral

26.

Tchernof A, Poehlman ET, Després JP (2000) Body fat distribution, the menopause transition, and hormone replacement therapy. Diabetes Metab 26(1):12–20PubMed

27.

Maltais ML, Desroches J, Dionne IJ (2009) Changes in muscle mass and strength after menopause. J Musculoskelet Neuronal Interact 9(4):186–197PubMed

28.

Fu X, Ma X, Lu H, He W, Wang Z, Zhu S (2011) Associations of fat mass and fat distribution with bone mineral density in pre- and postmenopausal Chinese women. Osteoporos Int 22(1):113–119. https://doi.org/10.1007/s00198-010-1210-9 CrossRefPubMed

29.

Nelson CA, Warren JT, Wang MWH, Teitelbaum SL, Fremont DH (2012) RANKL employs distinct binding modes to engage RANK and the osteoprotegerin decoy receptor. Structure 20(11):1971–1982. https://doi.org/10.1016/j.str.2012.08.030 CrossRefPubMedPubMedCentral

30.

Wada T, Nakashima T, Hiroshi N, Penninger JM (2006) RANKL-RANK signaling in osteoclastogenesis and bone disease. Trends Mol Med 12(1):17–25. https://doi.org/10.1016/j.molmed.2005.11.007 CrossRefPubMed

31.

Weichhaus M, Segaran P, Renaud A, Geerts D, Connelly L (2014) Osteoprotegerin expression in triple-negative breast cancer cells promotes metastasis. Cancer Med 3(5):1112–1125. https://doi.org/10.1002/cam4.277 CrossRefPubMedPubMedCentral

32.

Boyce BF, Xing L (2008) Functions of RANKL/RANK/OPG in bone modeling and remodeling. Arch Biochem Biophys 473(2):139–146. https://doi.org/10.1016/j.abb.2008.03.018 CrossRefPubMedPubMedCentral

33.

Boyce BF, Xing L (2007) Biology of RANK, RANKL, and osteoprotegerin. Arthritis Res Ther 9 Suppl 1:S1. Review

34.

Raisz LG (2005) Pathogenesis of osteoporosis: concepts, conflicts, and prospects. J Clin Invest 115(12):3318–3325. https://doi.org/10.1172/JCI27071 CrossRefPubMedPubMedCentral

35.

Kearns AE, Khosla S, Kostenuik PJ (2008) Receptor activator of nuclear factor кB ligand and osteoprotegerin regulation of bone remodeling in health and disease. Endocrine Rev 29(2):155–928. https://doi.org/10.1210/er.2007-0014

36.

Vega D, Maalouf NM, Sakhaee K (2007) The role of receptor activator of nuclear factor-휅B (RANK)/RANK ligand/osteoprotegerin: clinical implications. J Clin Endocrinol Metab 92(12):4514–4521. https://doi.org/10.1210/jc.2007-0646 CrossRefPubMed

37.

Nabipour I, Larijani B, Vahdat K, Assadi M, Jafari SM, Ahmadi E, Movahed A, Moradhaseli F, Sanjdideh Z, Obeidi N, Amiri Z (2009) Relationships among serum receptor of nuclear factor-kappaB ligand, osteoprotegerin, high-sensitivity C-reactive protein, and bone mineral density in postmenopausal women: osteoimmunity versus osteoinflammatory. Menopause 16(5):950–955. https://doi.org/10.1097/gme.0b013e3181a181b8 CrossRefPubMed

38.

Garrett JR, Boyce BF, Oreffo RO, Bonewald L, Poser J, Mundy GR (1990) Oxygen-derived free radicals stimulate osteoclastic bone resorption in rodent bone in vitro and in vivo. J Clin Invest 85(3):632–639. https://doi.org/10.1172/JCI114485 CrossRefPubMedPubMedCentral

39.

Bai XC, Lu D, Bai J, Zheng H, Ke ZY, Li XM, Luo SQ (2004) Oxidative stress inhibits osteoblastic differentiation of bone cells by ERK and NF-kappaB. Biochem Biophys Res Commun 314(1):197–207. https://doi.org/10.1016/j.bbrc.2003.12.073 CrossRefPubMed

40.

Cervellati C, Romani A, Cremonini E, Bergamini CM, Fila E, Squerzanti M, Greco P, Massari L, Bonaccorsi G (2016) Higher urinary levels of 8-hydroxy-2′-deoxyguanosine are associated with a worse RANKL/OPG ratio in postmenopausal women with osteopenia. Oxidative Med Cell Longev 2016:6038798CrossRef

41.

Wang Y, Park NY, Jang Y, Ma A, Jiang Q (2015) Vitamin E γ-tocotrienol inhibits cytokine-stimulated NF-κB activation by induction of anti-inflammatory A20 via stress adaptive response due to modulation of sphingolipids. J Immunol 195(1):126–133. https://doi.org/10.4049/jimmunol.1403149 CrossRefPubMedPubMedCentral

42.

Abd Manan N, Mohamed N, Shuid AN (2012) Effects of low-dose versus high-dose γ-tocotrienol on the bone cells exposed to the hydrogen peroxide-induced oxidative stress and apoptosis. Evid Based Complement Alternat Med 2012:680834CrossRefPubMedPubMedCentral

43.

Qureshi AA, Khan DA, Mahjabeen W, Trias AM, Silswal N, Qureshi N (2015) Impact of δ-Tocotrienol on inflammatory biomarkers and oxidative stress in hypercholesterolemic subjects. J Clin Exp Cardiolog 6(4):1000367

44.

Qureshi AA, Khan DA, Mahjabeen W, Qureshi N (2015) Dose-dependent modulation of lipid parameters, cytokines and RNA by δ-tocotrienol in hypercholesterolemic subjects restricted to AHA Step-1 diet. Br J Med Medical Res 6(4):351–366. https://doi.org/10.9734/BJMMR/2015/13820 CrossRef

Titel: Tocotrienol supplementation suppressed bone resorption and oxidative stress in postmenopausal osteopenic women: a 12-week randomized double-blinded placebo-controlled trial
verfasst von: C.-L. Shen
S. Yang
M. D. Tomison
A. W. Romero
C. K. Felton
H. Mo
Publikationsdatum: 12.01.2018
Verlag: Springer London
Erschienen in: Osteoporosis International / Ausgabe 4/2018
Print ISSN: 0937-941X
Elektronische ISSN: 1433-2965
DOI: https://doi.org/10.1007/s00198-017-4356-x

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Springer Medizin

Tocotrienol supplementation suppressed bone resorption and oxidative stress in postmenopausal osteopenic women: a 12-week randomized double-blinded placebo-controlled trial

Abstract

Summary

Introduction

Methods

Results

Conclusions

Trial registration

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Springer Medizin

Abstract

Summary

Introduction

Methods

Results

Conclusions

Trial registration

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