{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:49:34Z","timestamp":1787028574175,"version":"build-2736575974"},"reference-count":81,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T00:00:00Z","timestamp":1760918400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004515","name":"National University of Malaysia","doi-asserted-by":"publisher","award":["FF-349-2011"],"award-info":[{"award-number":["FF-349-2011"]}],"id":[{"id":"10.13039\/501100004515","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Malaysian Ministry of Science Technology and Innovation","award":["-"],"award-info":[{"award-number":["-"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Oxidative stress brought on by prolonged glucocorticoid therapy reduces bone growth, structure, and mechanical qualities. Free radicals promote osteoclastic activity and are harmful to osteoblasts. As an antioxidant, tocotrienol offers protection against illnesses linked to free radicals. Annatto tocotrienol (ATT) is a tocopherol-free tocotrienol, and palm tocotrienol (PTT) is a tocotrienol mixture. Finding out how ATT and PTT protect against glucocorticoid-induced osteoporosis was the aim of this study. In this study, 32 mature male Sprague-Dawley rats were employed. Twenty-four rats were divided into three groups: Dex, Dex + PTT, and Dex + ATT, after being adrenalectomized. A sham surgery was performed on the remaining eight rats. The Dex group received oral vehicle palm olein (0.1 mL\/kg\/day) and intramuscular injection of dexamethasone (120 \u00b5g\/kg\/day). Dexamethasone 120 \u00b5g\/kg\/day was administered intramuscularly to the Dex + PTT and Dex + ATT group, and palm tocotrienol (PTT) and annatto tocotrienol (ATT) 60 mg\/kg\/day were added as a supplement. Vehicle palm olein was administered intramuscularly to the sham-operated rats, 0.05 mL\/kg\/day and 0.1 mL\/kg\/day orally. The treatments were administered for two months before the rats were euthanized. The biomechanical strength of the femoral bones was evaluated, and the structural characteristics of bone histomorphometry were examined. According to the findings, prolonged glucocorticoid therapy resulted in decreased superoxide dismutase (SOD) activity, increased lipid peroxidation, and bone carboxy-terminal collagen cross-linkages (CTX). Bone Volume\/Tissue Volume (BV\/TV) and Trabecular Number (Tb.N) were drastically reduced, which severely reduced bone biomechanical strength. There were also alterations in the bone formation and resorption gene expressions. Lipid peroxidation, CTX levels, and SOD activity were all considerably maintained at control levels by PTT and ATT intake. Additionally, it preserved the biomechanical strength and bone structure, as well as maintaining the gene expressions. According to the study\u2019s findings, ATT and PTT may have anabolic and anti-resorptive properties and have the potential to be utilized as a prophylactic for individuals receiving long-term glucocorticoid therapy.<\/jats:p>","DOI":"10.3390\/ijms262010206","type":"journal-article","created":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T15:20:12Z","timestamp":1760973612000},"page":"10206","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Comparative Bone-Protective Effects of Tocotrienol Isomers from Palm and Annatto in Dexamethasone-Induced Osteoporotic Male Rats"],"prefix":"10.3390","volume":"26","author":[{"given":"Elvy Suhana Mohd","family":"Ramli","sequence":"first","affiliation":[{"name":"Department of Anatomy, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Cheras, Kuala Lumpur 56000, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2452-6459","authenticated-orcid":false,"given":"Fairus","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Cheras, Kuala Lumpur 56000, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nur Aqilah","family":"Kamaruddin","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Cheras, Kuala Lumpur 56000, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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, Cheras, Kuala Lumpur 56000, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9655-438X","authenticated-orcid":false,"given":"Ima Nirwana","family":"Soelaiman","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Cheras, Kuala Lumpur 56000, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2219-6297","authenticated-orcid":false,"given":"Kok-Lun","family":"Pang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Cheras, Kuala Lumpur 56000, Malaysia"},{"name":"Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway, Subang Jaya 46150, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1007\/s00198-014-2883-2","article-title":"International management of bone health in glucocorticoid-exposed individuals in the observational GLOW study","volume":"26","author":"Silverman","year":"2014","journal-title":"Osteoporos. Int."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1023\/A:1010007108155","article-title":"Glucocorticoid-Induced Osteoporosis","volume":"2","author":"Weinstein","year":"2001","journal-title":"Rev. Endocr. Metab. Disord."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1016\/j.micron.2005.07.009","article-title":"Histomorphometric analysis of glucocorticoid-induced osteoporosis","volume":"36","author":"Carbonare","year":"2005","journal-title":"Micron"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Wang, L.T., Chen, L.R., and Chen, K.H. (2023). Hormone-Related and Drug-Induced Osteoporosis: A Cellular and Molecular Overview. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24065814"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1172\/JCI0214538","article-title":"Promotion of osteoclast survival and antagonism of bisphosphonate-induced osteoclast apoptosis by glucocorticoids","volume":"109","author":"Weinstein","year":"2002","journal-title":"J. Clin. Investig."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1016\/j.biopha.2018.11.103","article-title":"Dexamethasone induces osteoblast apoptosis through ROS-PI3K\/AKT\/GSK3\u03b2 signaling pathway","volume":"110","author":"Deng","year":"2019","journal-title":"Biomed Pharmacother"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1172\/JCI116273","article-title":"An evaluation of several biochemical markers for bone formation and resorption in a protocol utilizing cyclical parathyroid hormone and calcitonin therapy for osteoporosis","volume":"91","author":"Hodsman","year":"1993","journal-title":"J. Clin. Investig."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1359\/jbmr.1997.12.5.734","article-title":"Dexamethasone Stimulates Osteoclast-like Cell Formation by Directly Acting on Hemopoietic Blast Cells and Enhances Osteoclast-like Cell Formation Stimulated by Parathyroid Hormone and Prostaglandin E2","volume":"12","author":"Kaji","year":"1997","journal-title":"J. Bone Miner. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"E587","DOI":"10.1152\/ajpendo.00219.2016","article-title":"Cortical bone loss caused by glucocorticoid excess requires RANKL production by osteocytes and is associated with reduced OPG expression in mice","volume":"311","author":"Piemontese","year":"2016","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.cytogfr.2023.03.002","article-title":"Pathogenic mechanisms of glucocorticoid-induced osteoporosis","volume":"70","author":"Chen","year":"2023","journal-title":"Cytokine Growth Factor Rev"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.3109\/10715762.2010.498478","article-title":"Pathological aspects of lipid peroxidation","volume":"44","author":"Auge","year":"2010","journal-title":"Free Radic. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1172\/JCI114485","article-title":"Oxygen-derived free radicals stimulate osteoclastic bone resorption in rodent bone in vitro and in vivo","volume":"85","author":"Garrett","year":"1990","journal-title":"J. Clin. Investig."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2346","DOI":"10.1161\/01.ATV.20.11.2346","article-title":"Role of Lipids in Osteoporosis","volume":"20","author":"Parhami","year":"2000","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Guo, T., Zhang, L., Konermann, A., Zhou, H., Jin, F., and Liu, W. (2015). Manganese superoxide dismutase is required to maintain osteoclast differentiation and function under static force. Sci. Rep., 5.","DOI":"10.1038\/srep08016"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"217","DOI":"10.2991\/efood.k.200427.001","article-title":"Tocotrienols in Bone Protection: Evidence from Preclinical Studies","volume":"1","author":"Meister","year":"2020","journal-title":"eFood"},{"key":"ref_16","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: Its potential against cancer and other chronic diseases","volume":"80","author":"Aggarwal","year":"2010","journal-title":"Biochem. Pharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1111\/j.1440-1681.2005.04264.x","article-title":"Tocotrienol offers better protection than tocopherol from free radical-induced damage of rat bone","volume":"32","author":"Ahmad","year":"2005","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1007\/BF00298885","article-title":"Vitamin E stimulates trabecular bone formation and alters epiphyseal cartilage morphometry","volume":"57","author":"Xu","year":"1995","journal-title":"Calcif. Tissue Int."},{"key":"ref_19","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_20","doi-asserted-by":"crossref","first-page":"e012572","DOI":"10.1136\/bmjopen-2016-012572","article-title":"Safety and efficacy of tocotrienol supplementation for bone health in postmenopausal women: Protocol for a dose-response double-blinded placebo-controlled randomised trial","volume":"6","author":"Shen","year":"2016","journal-title":"BMJ Open"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1186\/1743-7075-11-52","article-title":"Pharmacological potential of tocotrienols: A review","volume":"11","author":"Ahsan","year":"2014","journal-title":"Nutr. Metab."},{"key":"ref_22","first-page":"960742","article-title":"Effects of Tocotrienol and Lovastatin Combination on Osteoblast and Osteoclast Activity in Estrogen-Deficient Osteoporosis. Evidence-Based Complement","volume":"2012","author":"Mohamed","year":"2012","journal-title":"Altern. Med."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Chin, K.Y. (2024). Updates in the skeletal and joint protective effects of tocotrienol: A mini review. Front. Endocrinol., 15.","DOI":"10.3389\/fendo.2024.1417191"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1385\/JCD:7:3:255","article-title":"Relationship between changes in bone mineral density and vertebral fracture risk associated with risedronate: Greater increases in bone mineral density do not relate to greater decreases in fracture risk","volume":"7","author":"Watts","year":"2004","journal-title":"J. Clin. Densitom."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/S8756-3282(01)00483-5","article-title":"Male rodent model of age-related bone loss in men","volume":"29","author":"Wang","year":"2001","journal-title":"Bone"},{"key":"ref_26","first-page":"786","article-title":"Effect of 11\u03b2-HSD1 dehydrogenase activity on bone histomorphometry of glucocorticoid-induced osteoporotic male Sprague-Dawley rats","volume":"52","author":"Suhana","year":"2011","journal-title":"Singap. Med. J."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1089\/109662004322984699","article-title":"Effects of Tocopherols and Tocotrienols on Body Composition and Bone Calcium Content in Adrenalectomized Rats Replaced with Dexamethasone","volume":"7","author":"Suhaniza","year":"2004","journal-title":"J. Med. Food"},{"key":"ref_28","first-page":"726590","article-title":"Effects of Nrf2 Deficiency on Bone Microarchitecture in an Experimental Model of Osteoporosis. Oxidative Med","volume":"2014","author":"Brines","year":"2014","journal-title":"Cell. Longev."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2381","DOI":"10.1002\/jbmr.1973","article-title":"Lipoproteins are an important bacterial component responsible for bone destruction through the induction of osteoclast differentiation and activation","volume":"28","author":"Kim","year":"2013","journal-title":"J. Bone Miner. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1007\/s00223-010-9393-9","article-title":"Association of oxidative stress with postmenopausal osteoporosis and the effects of hydrogen peroxide on osteoclast formation in human bone marrow cell cultures","volume":"87","author":"Baek","year":"2010","journal-title":"Calcif. Tissue Int."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1161\/01.ATV.17.4.680","article-title":"Lipid oxidation products have opposite effects on calcifying vascular cell and bone cell differentiation. A possible explanation for the paradox of arterial calcification in osteoporotic patients","volume":"17","author":"Parhami","year":"1997","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/S0891-5849(02)01197-8","article-title":"Biological significance of phospholipid hydroperoxide glutathione peroxidase (PHGPx, GPx4) in mammalian cells","volume":"34","author":"Imai","year":"2003","journal-title":"Free Radic. Biol. Med."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Zhu, L.-J., Liu, M.-Y., Li, H., Liu, X., Chen, C., Han, Z., Wu, H.-Y., Jing, X., Zhou, H.-H., and Suh, H. (2014). The different roles of glucocorticoids in the hippocampus and hypothalamus in chronic stress-induced HPA axis hyperactivity. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0097689"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1016\/j.bbrc.2005.08.072","article-title":"Lipid peroxidation: Mechanisms, inhibition, and biological effects","volume":"338","author":"Niki","year":"2005","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1038\/s41574-020-0341-0","article-title":"Pathogenesis of glucocorticoid-induced osteoporosis and options for treatment","volume":"16","author":"Chotiyarnwong","year":"2020","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"505","DOI":"10.5114\/aoms.2010.14460","article-title":"Vitamin E reversed nicotine-induced toxic effects on bone biochemical markers in male rats","volume":"4","author":"Norazlina","year":"2010","journal-title":"Arch. Med. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.2147\/CIA.S67016","article-title":"Effects of annatto-derived tocotrienol supplementation on osteoporosis induced by testosterone deficiency in rats","volume":"9","author":"Chin","year":"2014","journal-title":"Clin. Interv. Aging"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"532862","DOI":"10.1155\/2012\/532862","article-title":"Palm tocotrienol supplementation enhanced bone formation in oestrogen-deficient rats","volume":"2012","author":"Soelaiman","year":"2012","journal-title":"Int. J. Endocrinol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"54","DOI":"10.53879\/id.56.11.11848","article-title":"Effect of glucocorticoids exposure on serum osteocalcin levels","volume":"56","author":"Holla","year":"2019","journal-title":"Indian Drugs"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/S0749-0690(02)00098-8","article-title":"The pathophysiology of bone loss","volume":"19","author":"Dempster","year":"2003","journal-title":"Clin. Geriatr. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1359\/jbmr.2000.15.4.754","article-title":"Effects of alendronate on bone quality and remodeling in glucocorticoid-induced osteoporosis: A histomorphometric analysis of transiliac biopsies","volume":"15","author":"Chavassieux","year":"2000","journal-title":"J. Bone Miner. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1172\/JCI2799","article-title":"Inhibition of osteoblastogenesis and promotion of apoptosis of osteoblasts and osteocytes by glucocorticoids. Potential mechanisms of their deleterious effects on bone","volume":"102","author":"Weinstein","year":"1998","journal-title":"J. Clin. Investig."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.bone.2014.12.004","article-title":"A joined role of canopy and reversal cells in bone remodeling\u2014Lessons from glucocorticoid-induced osteoporosis","volume":"73","author":"Jensen","year":"2015","journal-title":"Bone"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1007\/s11154-006-9009-x","article-title":"Molecular regulation of osteoclast activity","volume":"7","author":"Bruzzaniti","year":"2006","journal-title":"Rev. Endocr. Metab. Disord."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1016\/j.bone.2003.11.026","article-title":"Perspectives on glucocorticoid-induced osteoporosis","volume":"34","author":"Canalis","year":"2004","journal-title":"Bone"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"70","DOI":"10.4103\/CJP.CJP_7_19","article-title":"Different susceptibilities of osteoclasts and osteoblasts to glucocorticoid-induced oxidative stress and mitochondrial alterations","volume":"62","author":"Chen","year":"2019","journal-title":"Chin J Physiol"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1136\/ard.57.6.325","article-title":"Should we look for osteoporosis in patients with rheumatoid arthritis?","volume":"57","author":"Lems","year":"1998","journal-title":"Ann. Rheum. Dis."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1007\/BF02968254","article-title":"Dexamethasone inhibits the formation of multinucleated osteoclastsvia down-regulation of \u03b23 integrin expression","volume":"29","author":"Kim","year":"2006","journal-title":"Arch. Pharmacal Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3366","DOI":"10.1096\/fj.11-182519","article-title":"Glucocorticoid dose determines osteocyte cell fate","volume":"25","author":"Jia","year":"2011","journal-title":"FASEB J."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2184","DOI":"10.1002\/jbmr.113","article-title":"Glucocorticoids maintain human osteoclasts in the active mode of their resorption cycle","volume":"25","year":"2010","journal-title":"J. Bone Miner. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"3306","DOI":"10.1016\/j.bbamcr.2013.09.020","article-title":"Dexamethasone increases \u03b1v\u03b23 integrin expression and affinity through a calcineurin\/NFAT pathway","volume":"1833","author":"Faralli","year":"2013","journal-title":"Biochim. Biophys. Acta BBA Mol. Cell Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"4473","DOI":"10.1073\/pnas.87.12.4473","article-title":"Osteopontin\u2014A possible anchor of osteoclasts to bone","volume":"87","author":"Reinholt","year":"1990","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"33","DOI":"10.3109\/00365513.2015.1087045","article-title":"Serum osteopontin levels in relation to bone mineral density and bone turnover markers in postmenopausal women","volume":"76","author":"Wei","year":"2015","journal-title":"Scand. J. Clin. Lab. Investig."},{"key":"ref_54","first-page":"268","article-title":"The OPG\/RANKL\/RANK system in metabolic bone diseases","volume":"4","author":"Hofbauer","year":"2004","journal-title":"J. Musculoskelet. Neuronal Interact."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1359\/JBMR.041233","article-title":"Influence of Glucocorticoids on Human Osteoclast Generation and Activity","volume":"20","author":"Sivagurunathan","year":"2005","journal-title":"J. Bone Miner. Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"4382","DOI":"10.1210\/endo.140.10.7034","article-title":"Stimulation of osteoprotegerin ligand and inhibition of osteoprotegerin production by glucocorticoids in human osteoblastic lineage cells: Potential paracrine mechanisms of glucocorticoid-induced osteoporosis","volume":"140","author":"Hofbauer","year":"1999","journal-title":"Endocrinology"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1002\/ar.10121","article-title":"Regulation of osteoclast differentiation and function by receptor activator of NFkB ligand and osteoprotegerin","volume":"268","author":"Shiotani","year":"2002","journal-title":"Anat. Rec."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1007\/BF00296340","article-title":"Acute effects of deflazacort and prednisone on rates of mineralization and bone formation","volume":"56","author":"Cascio","year":"1995","journal-title":"Calcif. Tissue Int."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1007\/978-1-4939-2895-8_8","article-title":"Glucocorticoid-Induced Osteoporosis","volume":"Volume 872","author":"Frenkel","year":"2015","journal-title":"Advances in Experimental Medicine and Biology"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1007\/BF02405069","article-title":"Mean wall thickness and formation periods of trabecular bone packets in corticosteroid-induced osteoporosis","volume":"35","author":"Dempster","year":"1983","journal-title":"Calcif. Tissue Int."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"S11","DOI":"10.1016\/S0020-1383(16)47003-8","article-title":"Bone mechanical properties and changes with osteoporosis","volume":"47","author":"Osterhoff","year":"2016","journal-title":"Injury"},{"key":"ref_62","first-page":"247","article-title":"Effects of Palm Tocotrienols on Oxidative Stress and Bone Strength in Ovariectomised Rats","volume":"3","author":"Shuid","year":"2008","journal-title":"Med. Health"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1007\/s00774-009-0122-2","article-title":"Vitamin E exhibits bone anabolic actions in normal male rats","volume":"28","author":"Shuid","year":"2010","journal-title":"J. Bone Min. Metab."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.2174\/13894501113149990178","article-title":"A Review of the Possible Mechanisms of Action of Tocotrienol\u2014A Potential Antiosteoporotic Agent","volume":"14","author":"Chin","year":"2013","journal-title":"Curr. Drug Targets"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1172\/JCI6800","article-title":"Prevention of osteocyte and osteoblast apoptosis by bisphosphonates and calcitonin","volume":"104","author":"Plotkin","year":"1999","journal-title":"J. Clin. Investig."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1016\/j.bone.2009.06.030","article-title":"Glucocorticoids, osteocytes, and skeletal fragility: The role of bone vascularity","volume":"46","author":"Weinstein","year":"2010","journal-title":"Bone"},{"key":"ref_67","first-page":"216","article-title":"Circadian and circatrigintan changes in osteoblastic activity assessed by serum osteocalcin. Physiological and methodological aspects","volume":"41","author":"Nielsen","year":"1994","journal-title":"Dan. Med. Bull."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"4974","DOI":"10.3390\/nu6114974","article-title":"Annatto Tocotrienol Improves Indices of Bone Static Histomorphometry in Osteoporosis Due to Testosterone Deficiency in Rats","volume":"6","author":"Chin","year":"2014","journal-title":"Nutrients"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Mohamad, N.-V., Ima-Nirwana, S., and Chin, K.-Y. (2021). Therapeutic potential of annatto tocotrienol with self-emulsifying drug delivery system in a rat model of postmenopausal bone loss. Biomed. Pharmacother., 137.","DOI":"10.1016\/j.biopha.2021.111368"},{"key":"ref_70","first-page":"85","article-title":"Beneficial Effects of Annatto (Bixa orellana) Tocotrienol on Bone Histomorphometry and Expression of Genes Related to Bone Formation and Resorption in Osteoporosis Induced by Dexamethasone","volume":"7","author":"Ramli","year":"2018","journal-title":"Int. J. Med. Res. Health Sci."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1111\/j.1742-7843.2008.00241.x","article-title":"Palm Tocotrienol Exerted Better Antioxidant Activities in Bone than \u03b1-Tocopherol","volume":"103","author":"Maniam","year":"2008","journal-title":"Basic Clin. Pharmacol. Toxicol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1038\/nm.2659","article-title":"Vitamin E decreases bone mass by stimulating osteoclast fusion","volume":"18","author":"Fujita","year":"2012","journal-title":"Nat. Med."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1007\/s00223-008-9190-x","article-title":"Beneficial effects of tocotrienol and tocopherol on bone histomorphometric parameters in sprague-dawley male rats after nicotine cessation","volume":"84","author":"Hermizi","year":"2009","journal-title":"Calcif. Tissue Int."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"369S","DOI":"10.1093\/jn\/131.2.369S","article-title":"Molecular Aspects of \u03b1-Tocotrienol Antioxidant Action and Cell Signalling","volume":"131","author":"Packer","year":"2001","journal-title":"J. Nutr."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1002\/jcb.240560308","article-title":"Blockade of osteoclast-mediated bone resorption through occupancy of the integrin receptor: A potential approach to the therapy of osteoporosis","volume":"56","author":"Rosenblatt","year":"1994","journal-title":"J. Cell. Biochem."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1007\/s00223-002-1090-x","article-title":"Osteopontin facilitates bone resorption, decreasing bone mineral crystallinity and content during calcium deficiency","volume":"73","author":"Shapses","year":"2003","journal-title":"Calcif. Tissue Int."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1038\/nm1270","article-title":"NFAT and Osterix cooperatively regulate bone formation","volume":"11","author":"Koga","year":"2005","journal-title":"Nat. Med."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"656025","DOI":"10.1155\/2012\/656025","article-title":"Effects of Palm Vitamin E on Bone-Formation-Related Gene Expression in Nicotine-Treated Rats","volume":"2012","author":"Abukhadir","year":"2012","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1359\/jbmr.2000.15.5.872","article-title":"Diet- or warfarin-induced vitamin K insufficiency elevates circulating undercarboxylated osteocalcin without altering skeletal status in growing female rats","volume":"15","author":"Haffa","year":"2000","journal-title":"J. Bone Miner. Res."},{"key":"ref_80","first-page":"527","article-title":"Determinants of skeletal fragility and bone quality","volume":"2","author":"Turner","year":"2002","journal-title":"J. Musculoskelet. Neuronal Interact."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1002\/jbmr.5650020617","article-title":"Bone histomorphometry: Standardization of nomenclature, symbols, and units. Report of the ASBMR Histomorphometry Nomenclature Committee","volume":"2","author":"Parfitt","year":"1987","journal-title":"J. Bone Miner. Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/20\/10206\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T04:28:21Z","timestamp":1761107301000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/20\/10206"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,20]]},"references-count":81,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["ijms262010206"],"URL":"https:\/\/doi.org\/10.3390\/ijms262010206","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,20]]}}}