{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T07:09:02Z","timestamp":1774422542089,"version":"3.50.1"},"reference-count":61,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2019,9,9]],"date-time":"2019-09-09T00:00:00Z","timestamp":1567987200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004515","name":"Universiti Kebangsaan Malaysia","doi-asserted-by":"publisher","award":["MI-2019-006"],"award-info":[{"award-number":["MI-2019-006"]}],"id":[{"id":"10.13039\/501100004515","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004515","name":"Universiti Kebangsaan Malaysia","doi-asserted-by":"publisher","award":["FF-2018-410"],"award-info":[{"award-number":["FF-2018-410"]}],"id":[{"id":"10.13039\/501100004515","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJERPH"],"abstract":"<jats:p>A positive association between metabolic syndrome (MetS) and osteoporosis has been demonstrated in previous animal studies. The mechanisms of MetS in orchestrating the bone remodelling process have traditionally focused on the interactions between mature osteoblasts and osteoclasts, while the role of osteocytes is unexplored. Our earlier studies demonstrated the bone-promoting effects of tocotrienol using a rat model of osteoporosis induced by MetS. This study aimed to investigate the expression of osteocyte-derived peptides in the bone of rats with MetS-induced osteoporosis treated with tocotrienol. Age-matched male Wistar rats (12-week-old; n = 42) were divided into seven experimental groups. Two groups served as the baseline and normal group, respectively. The other five groups were fed with a high-carbohydrate high-fat (HCHF) diet to induce MetS. The five groups of HCHF animals were treated with tocopherol-stripped corn oil (vehicle), annatto tocotrienol (60 and 100 mg\/kg), and palm tocotrienol (60 and 100 mg\/kg) starting from week 8. At the end of the study, the rats were sacrificed and their right tibias were harvested. Protein was extracted from the metaphyseal region of the proximal right tibia and levels of bone peptides, including osteoprotegerin (OPG), soluble receptor activator of nuclear factor-kappa B ligand (sRANKL), sclerostin (SOST), Dickkopf-related protein 1 (DKK-1), fibroblast growth factor-23 (FGF-23), and parathyroid hormone (PTH), were measured. The vehicle-treated animals displayed higher levels of sRANKL, SOST, DKK-1, FGF-23, and PTH as compared to the normal animals. Oral supplementation of annatto and palm tocotrienol (60 and 100 mg\/kg) reduced the levels of sRANKL and FGF-23 in the HCHF animals. Only 100 mg\/kg annatto and palm tocotrienol lowered SOST and DKK-1 levels in the HCHF animals. In conclusion, tocotrienol exerts potential skeletal-promoting benefit by modulating the levels of osteocytes-derived bone-related peptides.<\/jats:p>","DOI":"10.3390\/ijerph16183313","type":"journal-article","created":{"date-parts":[[2019,9,9]],"date-time":"2019-09-09T11:26:17Z","timestamp":1568028377000},"page":"3313","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["The Effects of Tocotrienol on Bone Peptides in a Rat Model of Osteoporosis Induced by Metabolic Syndrome: The Possible Communication between Bone Cells"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1184-4551","authenticated-orcid":false,"given":"Sok Kuan","family":"Wong","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak, Cheras 56000, Kuala Lumpur, Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6628-1552","authenticated-orcid":false,"given":"Kok-Yong","family":"Chin","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak, Cheras 56000, Kuala Lumpur, Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9655-438X","authenticated-orcid":false,"given":"Soelaiman","family":"Ima-Nirwana","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak, Cheras 56000, Kuala Lumpur, Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,9,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Wong, S.K., Chin, K.-Y., Suhaimi, F.H., Ahmad, F., and Ima-Nirwana, S. (2016). The Relationship between Metabolic Syndrome and Osteoporosis: A Review. Nutrients, 8.","DOI":"10.3390\/nu8060347"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1055\/s-0043-119352","article-title":"The Effects of a Modified High-carbohydrate High-fat Diet on Metabolic Syndrome Parameters in Male Rats","volume":"126","author":"Wong","year":"2018","journal-title":"Exp. Clin. Endocrinol. Diabetes"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Wong, S.K., Chin, K.-Y., Suhaimi, F.H., Ahmad, F., and Ima-Nirwana, S. (2018). Effects of metabolic syndrome on bone mineral density, histomorphometry and remodelling markers in male rats. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0192416"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.biopha.2017.12.042","article-title":"Osteoporosis is associated with metabolic syndrome induced by high-carbohydrate high-fat diet in a rat model","volume":"98","author":"Wong","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1007\/s40610-015-0026-y","article-title":"Osteocytes and Skeletal Pathophysiology","volume":"1","author":"Bellido","year":"2015","journal-title":"Curr. Mol. Boil. Rep."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1007\/s00223-013-9774-y","article-title":"Osteocyte-driven bone remodeling","volume":"94","author":"Bellido","year":"2014","journal-title":"Calcif. Tissue Int."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1038\/nm.3074","article-title":"WNT signaling in bone homeostasis and disease: From human mutations to treatments","volume":"19","author":"Baron","year":"2013","journal-title":"Nat. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"5050","DOI":"10.1210\/endo.142.12.8536","article-title":"Minireview: The OPG\/RANKL\/RANK System","volume":"142","author":"Khosla","year":"2001","journal-title":"Endocrinology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1016\/j.bbrc.2004.11.069","article-title":"Parathyroid hormone and parathyroid hormone-related peptide, and their receptors","volume":"328","author":"Gensure","year":"2005","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"S24","DOI":"10.1038\/ki.2011.27","article-title":"Phosphate and FGF-23","volume":"79","year":"2011","journal-title":"Kidney Int."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"F1577","DOI":"10.1152\/ajprenal.00463.2006","article-title":"Fibroblast growth factor 23 impairs phosphorus and vitamin D metabolism in vivo and suppresses 25-hydroxyvitamin D-1alpha-hydroxylase expression in vitro","volume":"293","author":"Perwad","year":"2007","journal-title":"Am. J. Physiol. Renal. Physiol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Wong, S.K., Mohamad, N.V., Ibrahim, N., Chin, K.Y., Shuid, A.N., and Ima-Nirwana, S. (2019). The Molecular Mechanism of Vitamin E as a Bone-Protecting Agent: A Review on Current Evidence. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20061453"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1613","DOI":"10.1016\/j.bcp.2010.07.043","article-title":"Tocotrienols, the Vitamin E of the 21st Century: It\u2019s Potential Against Cancer and Other Chronic Diseases","volume":"80","author":"Aggarwal","year":"2010","journal-title":"Biochem. Pharmacol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"444","DOI":"10.3389\/fphar.2017.00444","article-title":"As a Potential Interventional Treatment for Metabolic Syndrome: Evidence from Animal and Human Studies","volume":"8","author":"Wong","year":"2017","journal-title":"Front. Pharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2049","DOI":"10.2147\/DDDT.S79660","article-title":"The biological effects of tocotrienol on bone: A review on evidence from rodent models","volume":"9","author":"Chin","year":"2015","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Chin, K.-Y., and Ima-Nirwana, S. (2019). The Role of Tocotrienol in Preventing Male Osteoporosis\u2014A Review of Current Evidence. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20061355"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1038\/ijo.2014.124","article-title":"Gamma-tocotrienol attenuates high-fat diet-induced obesity and insulin resistance by inhibiting adipose inflammation and M1 macrophage recruitment","volume":"39","author":"Zhao","year":"2015","journal-title":"Int. J. Obes."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/j.lfs.2008.12.014","article-title":"Attenuation of diabetic nephropathy by tocotrienol: Involvement of NFkB signaling pathway","volume":"84","author":"Kuhad","year":"2009","journal-title":"Life Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1007\/s11745-012-3659-0","article-title":"Tocotrienol Attenuates Triglyceride Accumulation in HepG2 Cells and F344 Rats","volume":"47","author":"Burdeos","year":"2012","journal-title":"Lipids"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"5361","DOI":"10.1021\/acs.jafc.6b02228","article-title":"Alpha-Tocopherol Attenuates the Triglyceride- and Cholesterol-Lowering Effects of Rice Bran Tocotrienol in Rats Fed a Western Diet","volume":"64","author":"Shibata","year":"2016","journal-title":"J. Agric. Food Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.bone.2018.07.003","article-title":"Exploring the potential of tocotrienol from Bixa orellana as a single agent targeting metabolic syndrome and bone loss","volume":"116","author":"Wong","year":"2018","journal-title":"Bone"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Wong, S.K., Chin, K.-Y., Suhaimi, F.H., Ahmad, F., and Ima-Nirwana, S. (2018). The Effects of Vitamin E from Elaeis guineensis (Oil Palm) in a Rat Model of Bone Loss Due to Metabolic Syndrome. Int. J. Environ. Res. Public Heal., 15.","DOI":"10.3390\/ijerph15091828"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.jff.2018.03.022","article-title":"The effects of palm tocotrienol on metabolic syndrome and bone loss in male rats induced by high-carbohydrate high-fat diet","volume":"44","author":"Wong","year":"2018","journal-title":"J. Funct. Foods"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.3892\/mmr.2017.6160","article-title":"Inhibitory effects of vitamin E on osteocyte apoptosis and DNA oxidative damage in bone marrow hemopoietic cells at early stage of steroid-induced femoral head necrosis","volume":"15","author":"Jia","year":"2017","journal-title":"Mol. Med. Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1007\/s00223-018-0487-0","article-title":"Inhibition of Osteocyte Membrane Repair Activity via Dietary Vitamin E Deprivation Impairs Osteocyte Survival","volume":"104","author":"Hagan","year":"2019","journal-title":"Calcif. Tissue Int."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Casati, L., Pagani, F., Limonta, P., Vanetti, C., Stancari, G., and Sibilia, V. (2019). Beneficial effects of delta-tocotrienol against oxidative stress in osteoblastic cells: Studies on the mechanisms of action. Eur. J. Nutr., 1\u201313.","DOI":"10.1007\/s00394-019-02047-9"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.abb.2008.03.018","article-title":"Functions of RANKL\/RANK\/OPG in bone modeling and remodeling","volume":"473","author":"Boyce","year":"2008","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1038\/nm.2452","article-title":"Evidence for osteocyte regulation of bone homeostasis through RANKL expression","volume":"17","author":"Nakashima","year":"2011","journal-title":"Nat. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1038\/nm.2448","article-title":"Matrix-embedded cells control osteoclast formation","volume":"17","author":"Xiong","year":"2011","journal-title":"Nat. Med."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"O\u2019Brien, C.A., Plotkin, L.I., Galli, C., Goellner, J.J., Gort\u00e1zar, A.R., Allen, M.R., Robling, A.G., Bouxsein, M., Schipani, E., and Turner, C.H. (2008). Control of Bone Mass and Remodeling by PTH Receptor Signaling in Osteocytes. PLoS ONE, 3.","DOI":"10.1371\/journal.pone.0002942"},{"key":"ref_31","first-page":"S16","article-title":"Conditional deletion of the parathyroid hormone (PTH) receptor 1 from osteocytes results in decreased bone resorption and a progressive increase in cancellous bone mass","volume":"26","author":"Tu","year":"2011","journal-title":"J. Bone Miner. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1007\/s11914-007-0024-y","article-title":"The RANKL\/RANK\/OPG pathway","volume":"5","author":"Boyce","year":"2007","journal-title":"Curr. Osteoporos. Rep."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1038\/bonekey.2015.82","article-title":"The regulation of osteoclast differentiation by Wnt signals","volume":"4","author":"Kobayashi","year":"2015","journal-title":"BoneKEy Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3071","DOI":"10.1128\/MCB.01428-09","article-title":"Osteocyte Wnt\/beta-catenin signaling is required for normal bone homeostasis","volume":"30","author":"Kramer","year":"2010","journal-title":"Mol. Cell. Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"48868","DOI":"10.1074\/jbc.M208494200","article-title":"Parathyroid hormone stimulates receptor activator of NFkappa B ligand and inhibits osteoprotegerin expression via protein kinase A activation of cAMP-response element-binding protein","volume":"277","author":"Fu","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1002\/jbmr.320","article-title":"The amazing osteocyte","volume":"26","author":"Bonewald","year":"2011","journal-title":"J. Bone Miner. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"6267","DOI":"10.1093\/emboj\/cdg599","article-title":"Osteocyte control of bone formation via sclerostin, a novel BMP antagonist","volume":"22","author":"Winkler","year":"2003","journal-title":"EMBO J."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.cmet.2009.12.007","article-title":"Suppression of Wnt signaling by Dkk1 attenuates PTH-mediated stromal cell response and new bone formation","volume":"11","author":"Guo","year":"2010","journal-title":"Cell Metab."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1007\/s00774-010-0202-3","article-title":"Targeted overexpression of Dkk1 in osteoblasts reduces bone mass but does not impair the anabolic response to intermittent PTH treatment in mice","volume":"29","author":"Yao","year":"2011","journal-title":"J. Bone Mine.r Metab."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1359\/jbmr.090730","article-title":"Parathyroid hormone (PTH)-induced bone gain is blunted in SOST overexpressing and deficient mice","volume":"25","author":"Kramer","year":"2010","journal-title":"J. Bone Miner. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1016\/j.bone.2006.03.017","article-title":"Dkk1-mediated inhibition of Wnt signaling in bone results in osteopenia","volume":"39","author":"Li","year":"2006","journal-title":"Bone"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1359\/jbmr.080216","article-title":"Targeted Deletion of the Sclerostin Gene in Mice Results in Increased Bone Formation and Bone Strength","volume":"23","author":"Li","year":"2008","journal-title":"J. Bone Miner. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1359\/jbmr.060311","article-title":"Deletion of a Single Allele of the Dkk1 Gene Leads to an Increase in Bone Formation and Bone Mass","volume":"21","author":"Morvan","year":"2006","journal-title":"J. Bone Miner. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.bone.2007.05.009","article-title":"Bone mass is inversely proportional to Dkk1 levels in mice","volume":"41","author":"MacDonald","year":"2007","journal-title":"Bone"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"5866","DOI":"10.1074\/jbc.M705092200","article-title":"Mechanical stimulation of bone in vivo reduces osteocyte expression of Sost\/sclerostin","volume":"283","author":"Robling","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"5056","DOI":"10.1210\/jc.2010-0720","article-title":"Effects of Parathyroid Hormone Treatment on Circulating Sclerostin Levels in Postmenopausal Women","volume":"95","author":"Drake","year":"2010","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2215","DOI":"10.1002\/jbmr.2900","article-title":"Activation of Wnt Signaling by Mechanical Loading Is Impaired in the Bone of Old Mice","volume":"31","author":"Holguin","year":"2016","journal-title":"J. Bone Miner. Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1038\/ijos.2015.1","article-title":"Fibroblast growth factor 23 and bone mineralisation","volume":"7","author":"Guo","year":"2015","journal-title":"Int. J. Oral Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1038\/nature25451","article-title":"Alpha-Klotho is a non-enzymatic molecular scaffold for FGF23 hormone signalling","volume":"553","author":"Chen","year":"2018","journal-title":"Nature"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1007\/s00223-011-9501-5","article-title":"Fibroblast Growth Factor 23 (FGF23) and Alpha-Klotho Stimulate Osteoblastic MC3T3.E1 Cell Proliferation and Inhibit Mineralization","volume":"89","author":"Shalhoub","year":"2011","journal-title":"Calcif. Tissue Int."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/j.bone.2012.09.016","article-title":"Effects of PTH on osteocyte function","volume":"54","author":"Bellido","year":"2013","journal-title":"Bone"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1002\/jbm4.10021","article-title":"Parathyroid Hormone Signaling in Osteocytes","volume":"2","author":"Wein","year":"2017","journal-title":"JBMR Plus"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2075","DOI":"10.1002\/jbmr.1665","article-title":"Intermittent parathyroid hormone administration converts quiescent lining cells to active osteoblasts","volume":"27","author":"Kim","year":"2012","journal-title":"J. Bone Miner. Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.coph.2015.03.005","article-title":"Parathyroid hormone: Anabolic and catabolic actions on the skeleton","volume":"22","author":"Silva","year":"2015","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1002\/jbmr.541","article-title":"Adverse Effects of Hyperlipidemia on Bone Regeneration and Strength","volume":"27","author":"Pirih","year":"2012","journal-title":"J. Bone Miner. Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1549","DOI":"10.2337\/dc06-2438","article-title":"Vitamin D, Parathyroid Hormone Levels, and the Prevalence of Metabolic Syndrome in Community-Dwelling Older Adults","volume":"30","author":"Reis","year":"2007","journal-title":"Diabetes Care"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1016\/j.bbrc.2011.02.085","article-title":"alpha-Tocotrienol inhibits osteoclastic bone resorption by suppressing RANKL expression and signaling and bone resorbing activity","volume":"406","author":"Ha","year":"2011","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"S140","DOI":"10.1016\/j.bone.2009.01.446","article-title":"Trolox prevents osteoclastogenesis by suppressing RANKL expression and signaling","volume":"44","author":"Lee","year":"2009","journal-title":"Bone"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"12958","DOI":"10.3390\/ijerph121012958","article-title":"The Effects of Targeted Deliveries of Lovastatin and Tocotrienol on Ossification-Related Gene Expressions in Fracture Healing in an Osteoporosis Rat Model","volume":"12","author":"Ibrahim","year":"2015","journal-title":"Int. J. Environ. Res. Public Heal."},{"key":"ref_60","first-page":"14","article-title":"Effects of vitamin E on receptor activator of nuclear factor kappa B ligand (RANKL) and osteoprotegerin (OPG) in rats treated with nicotine","volume":"65","author":"Norazlina","year":"2010","journal-title":"Med J. Malays."},{"key":"ref_61","first-page":"623","article-title":"Vitamin E deficiency reduced lumbar bone calcium content in female rats","volume":"59","author":"Norazlina","year":"2004","journal-title":"Med J. Malays."}],"container-title":["International Journal of Environmental Research and Public Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-4601\/16\/18\/3313\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:17:58Z","timestamp":1760188678000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-4601\/16\/18\/3313"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,9,9]]},"references-count":61,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2019,9]]}},"alternative-id":["ijerph16183313"],"URL":"https:\/\/doi.org\/10.3390\/ijerph16183313","relation":{},"ISSN":["1660-4601"],"issn-type":[{"value":"1660-4601","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,9,9]]}}}