{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T15:35:02Z","timestamp":1792596902004,"version":"4.5.0"},"reference-count":165,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,1,7]],"date-time":"2021-01-07T00:00:00Z","timestamp":1609977600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["5R01 AR069562"],"award-info":[{"award-number":["5R01 AR069562"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["5R01 AR073156"],"award-info":[{"award-number":["5R01 AR073156"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2020R1A6A3A03037133"],"award-info":[{"award-number":["NRF-2020R1A6A3A03037133"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Bone is a dynamic tissue and is constantly being remodeled by bone cells. Metabolic reprogramming plays a critical role in the activation of these bone cells and skeletal metabolism, which fulfills the energy demand for bone remodeling. Among various metabolic pathways, the importance of lipid metabolism in bone cells has long been appreciated. More recent studies also establish the link between bone loss and lipid-altering conditions\u2014such as atherosclerotic vascular disease, hyperlipidemia, and obesity\u2014and uncover the detrimental effect of fat accumulation on skeletal homeostasis and increased risk of fracture. Targeting lipid metabolism with statin, a lipid-lowering drug, has been shown to improve bone density and quality in metabolic bone diseases. However, the molecular mechanisms of lipid-mediated regulation in osteoclasts are not completely understood. Thus, a better understanding of lipid metabolism in osteoclasts can be used to harness bone cell activity to treat pathological bone disorders. This review summarizes the recent developments of the contribution of lipid metabolism to the function and phenotype of osteoclasts.<\/jats:p>","DOI":"10.3390\/cells10010089","type":"journal-article","created":{"date-parts":[[2021,1,8]],"date-time":"2021-01-08T08:58:34Z","timestamp":1610096314000},"page":"89","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":101,"title":["Regulation of Osteoclast Differentiation and Activity by Lipid Metabolism"],"prefix":"10.3390","volume":"10","author":[{"given":"Haemin","family":"Kim","sequence":"first","affiliation":[{"name":"David Z. Rosensweig Genomics Research Center, Arthritis and Tissue Degeneration Program, Hospital for Special Surgery, New York, NY 10021, USA"},{"name":"Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2372-9131","authenticated-orcid":false,"given":"Brian","family":"Oh","sequence":"additional","affiliation":[{"name":"David Z. Rosensweig Genomics Research Center, Arthritis and Tissue Degeneration Program, Hospital for Special Surgery, New York, NY 10021, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyung-Hyun","family":"Park-Min","sequence":"additional","affiliation":[{"name":"David Z. Rosensweig Genomics Research Center, Arthritis and Tissue Degeneration Program, Hospital for Special Surgery, New York, NY 10021, USA"},{"name":"Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA"},{"name":"BCMB Allied Program, Weill Cornell Graduate School of Medical Science, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1146\/annurev-pathol-011110-130203","article-title":"Disorders of bone remodeling","volume":"6","author":"Feng","year":"2011","journal-title":"Annu. Rev. Pathol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1007\/s11154-010-9153-1","article-title":"Cellular mechanisms of bone remodeling","volume":"11","author":"Eriksen","year":"2010","journal-title":"Rev. Endocr. Metab. Disord."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1038\/s41577-019-0178-8","article-title":"Osteoimmunology: Evolving concepts in bone-immune interactions in health and disease","volume":"19","author":"Tsukasaki","year":"2019","journal-title":"Nat. Rev. Immunol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1038\/nature01658","article-title":"Osteoclast differentiation and activation","volume":"423","author":"Boyle","year":"2003","journal-title":"Nature"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"11","DOI":"10.4248\/BR201301003","article-title":"Osteoclasts: New Insights","volume":"1","author":"Feng","year":"2013","journal-title":"Bone Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2519","DOI":"10.1007\/s00018-018-2817-9","article-title":"Mechanisms involved in normal and pathological osteoclastogenesis","volume":"75","year":"2018","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1146\/annurev.pathmechdis.3.121806.151431","article-title":"The osteoclast: Friend or foe?","volume":"3","author":"Novack","year":"2008","journal-title":"Annu. Rev. Pathol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/nrm3254","article-title":"Building strong bones: Molecular regulation of the osteoblast lineage","volume":"13","author":"Long","year":"2011","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1210\/er.2012-1026","article-title":"The osteocyte: An endocrine cell ... and more","volume":"34","author":"Dallas","year":"2013","journal-title":"Endocr. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.plipres.2015.06.002","article-title":"Understanding the local actions of lipids in bone physiology","volume":"59","author":"During","year":"2015","journal-title":"Prog. Lipid Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1146\/annurev.nutr.012809.104655","article-title":"Bone metabolism in obesity and weight loss","volume":"32","author":"Shapses","year":"2012","journal-title":"Annu. Rev. Nutr."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/S0378-5122(99)00114-0","article-title":"Difference in the effect of adiposity on bone density between pre- and postmenopausal women","volume":"34","author":"Douchi","year":"2000","journal-title":"Maturitas"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.cmet.2019.09.015","article-title":"Lipids in the Bone Marrow: An Evolving Perspective","volume":"31","author":"Rosen","year":"2020","journal-title":"Cell Metab."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/S0022-2275(20)40456-0","article-title":"Lipid composition of normal human bone marrow as determined by column chromatography","volume":"3","author":"Lund","year":"1962","journal-title":"J. Lipid Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"24020","DOI":"10.1074\/jbc.R114.583658","article-title":"Molecular mechanisms of cellular cholesterol efflux","volume":"289","author":"Phillips","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1007\/s11883-015-0554-1","article-title":"HDL Cholesterol Efflux Capacity: Cardiovascular Risk Factor and Potential Therapeutic Target","volume":"18","author":"Bhatt","year":"2016","journal-title":"Curr. Atheroscler. Rep."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.coph.2020.03.002","article-title":"Nuclear receptors in osteoclasts","volume":"53","author":"Bae","year":"2020","journal-title":"Curr. Opin. Pharm."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.cell.2005.12.022","article-title":"Protein sensors for membrane sterols","volume":"124","author":"Goldstein","year":"2006","journal-title":"Cell"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1172\/JCI0215593","article-title":"SREBPs: Activators of the complete program of cholesterol and fatty acid synthesis in the liver","volume":"109","author":"Horton","year":"2002","journal-title":"J. Clin. Investig."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1016\/0888-7543(95)80009-B","article-title":"Structure of the human gene encoding sterol regulatory element binding protein-1 (SREBF1) and localization of SREBF1 and SREBF2 to chromosomes 17p11.2 and 22q13","volume":"25","author":"Hua","year":"1995","journal-title":"Genomics"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/S0092-8674(00)80213-5","article-title":"The SREBP pathway: Regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription factor","volume":"89","author":"Brown","year":"1997","journal-title":"Cell"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"11603","DOI":"10.1073\/pnas.90.24.11603","article-title":"SREBP-2, a second basic-helix-loop-helix-leucine zipper protein that stimulates transcription by binding to a sterol regulatory element","volume":"90","author":"Hua","year":"1993","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/0092-8674(94)90234-8","article-title":"SREBP-1, a membrane-bound transcription factor released by sterol-regulated proteolysis","volume":"77","author":"Wang","year":"1994","journal-title":"Cell"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"10379","DOI":"10.1074\/jbc.271.17.10379","article-title":"Regulated cleavage of sterol regulatory element binding proteins requires sequences on both sides of the endoplasmic reticulum membrane","volume":"271","author":"Hua","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1016\/S0092-8674(00)81304-5","article-title":"Sterol-regulated release of SREBP-2 from cell membranes requires two sequential cleavages, one within a transmembrane segment","volume":"85","author":"Sakai","year":"1996","journal-title":"Cell"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2432","DOI":"10.1016\/j.bbadis.2015.08.018","article-title":"Fatostatin, an SREBP inhibitor, prevented RANKL-induced bone loss by suppression of osteoclast differentiation","volume":"1852","author":"Inoue","year":"2015","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.bbadis.2018.10.026","article-title":"SREBP-2 aggravates breast cancer associated osteolysis by promoting osteoclastogenesis and breast cancer metastasis","volume":"1865","author":"Jie","year":"2019","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1038\/nrc.2016.76","article-title":"The interplay between cell signalling and the mevalonate pathway in cancer","volume":"16","author":"Mullen","year":"2016","journal-title":"Nat. Rev. Cancer"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1097\/MOL.0000000000000038","article-title":"Cholesterol precursors: More than mere markers of biosynthesis","volume":"25","author":"Brown","year":"2014","journal-title":"Curr. Opin. Lipidol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/S0021-9258(18)75823-7","article-title":"Synthesis and destuction of cholesterol in the organism","volume":"103","author":"Schoenheimer","year":"1933","journal-title":"J. Biol. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1126\/science.150.3692.19","article-title":"The biological synthesis of cholesterol","volume":"150","author":"Bloch","year":"1965","journal-title":"Science"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"18707","DOI":"10.1074\/jbc.R113.479808","article-title":"Controlling cholesterol synthesis beyond 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR)","volume":"288","author":"Sharpe","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"25264","DOI":"10.1016\/S0021-9258(19)74035-6","article-title":"Distinct sterol and nonsterol signals for the regulated degradation of 3-hydroxy-3-methylglutaryl-CoA reductase","volume":"267","author":"Roitelman","year":"1992","journal-title":"J. Biol. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/BF00054556","article-title":"Cholesterol biosynthesis and metabolism","volume":"6","author":"Russell","year":"1992","journal-title":"Cardiovasc. Drugs"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1016\/j.cmet.2008.10.008","article-title":"Switch-like control of SREBP-2 transport triggered by small changes in ER cholesterol: A delicate balance","volume":"8","author":"Radhakrishnan","year":"2008","journal-title":"Cell Metab."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1007\/s00774-009-0150-y","article-title":"Proteomic analysis of osteoclast lipid rafts: The role of the integrity of lipid rafts on V-ATPase activity in osteoclasts","volume":"28","author":"Ryu","year":"2010","journal-title":"J. Bone Miner. Metab."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"6522","DOI":"10.1074\/jbc.M114.598581","article-title":"Caveolin-1 regulates osteoclastogenesis and bone metabolism in a sex-dependent manner","volume":"290","author":"Lee","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3341","DOI":"10.1007\/s00018-012-1238-4","article-title":"Regulation of osteoclasts by membrane-derived lipid mediators","volume":"70","author":"Oikawa","year":"2013","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1016\/j.ajpath.2012.05.034","article-title":"Hypercholesterolemia promotes an osteoporotic phenotype","volume":"181","author":"Pelton","year":"2012","journal-title":"Am. J. Pathol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"R81","DOI":"10.1186\/ar4261","article-title":"Hypercholesterolemia boosts joint destruction in chronic arthritis. An experimental model aggravated by foam macrophage infiltration","volume":"15","author":"Gomez","year":"2013","journal-title":"Arthritis Res. Ther."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2165","DOI":"10.1902\/jop.2007.070181","article-title":"Oral administration of vitamin C prevents alveolar bone resorption induced by high dietary cholesterol in rats","volume":"78","author":"Sanbe","year":"2007","journal-title":"J. Periodontol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1038\/nri3520","article-title":"Macrophages in atherosclerosis: A dynamic balance","volume":"13","author":"Moore","year":"2013","journal-title":"Nat. Rev. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/S8756-3282(98)00082-9","article-title":"Involvement of cholesterol in osteoclast-like cell formation via cellular fusion","volume":"23","author":"Sato","year":"1998","journal-title":"Bone"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"19229","DOI":"10.1074\/jbc.M111.323600","article-title":"Low-density lipoprotein receptor deficiency causes impaired osteoclastogenesis and increased bone mass in mice because of defect in osteoclastic cell-cell fusion","volume":"287","author":"Okayasu","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"S108","DOI":"10.1038\/sj.cdd.4401399","article-title":"Osteoclast formation, survival and morphology are highly dependent on exogenous cholesterol\/lipoproteins","volume":"11","author":"Luegmayr","year":"2004","journal-title":"Cell Death Differ."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1093\/abbs\/gmy081","article-title":"HDL impairs osteoclastogenesis and induces osteoclast apoptosis via upregulation of ABCG1 expression","volume":"50","author":"Huang","year":"2018","journal-title":"Acta Biochim. Biophys. Sin."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1161\/01.ATV.20.4.1068","article-title":"Increased LDL cholesterol and atherosclerosis in LDL receptor-deficient mice with attenuated expression of scavenger receptor B1","volume":"20","author":"Huszar","year":"2000","journal-title":"Atheroscler. Thromb. Vasc. Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e6","DOI":"10.1161\/01.ATV.0000112023.62695.7f","article-title":"Hyperlipidemia promotes osteoclastic potential of bone marrow cells ex vivo","volume":"24","author":"Tintut","year":"2004","journal-title":"Atheroscler. Thromb. Vasc. Biol."},{"key":"ref_49","first-page":"11","article-title":"Bone-resorbing activity from cholesterol-exposed macrophages due to enhanced expression of interleukin-1alpha","volume":"81","author":"Sjogren","year":"2002","journal-title":"J. Dent. Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/j.cmet.2015.12.010","article-title":"Ligand Activation of ERRalpha by Cholesterol Mediates Statin and Bisphosphonate Effects","volume":"23","author":"Wei","year":"2016","journal-title":"Cell Metab."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1016\/j.cmet.2010.04.015","article-title":"PGC1beta mediates PPARgamma activation of osteoclastogenesis and rosiglitazone-induced bone loss","volume":"11","author":"Wei","year":"2010","journal-title":"Cell Metab."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2555","DOI":"10.1172\/JCI89935","article-title":"MYC-dependent oxidative metabolism regulates osteoclastogenesis via nuclear receptor ERRalpha","volume":"127","author":"Bae","year":"2017","journal-title":"J. Clin. Investig."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"3137","DOI":"10.1074\/jbc.272.6.3137","article-title":"Activation of the nuclear receptor LXR by oxysterols defines a new hormone response pathway","volume":"272","author":"Lehmann","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1038\/nature10280","article-title":"Oxysterols direct immune cell migration via EBI2","volume":"475","author":"Hannedouche","year":"2011","journal-title":"Nature"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1931","DOI":"10.1084\/jem.20150088","article-title":"Oxysterols and EBI2 promote osteoclast precursor migration to bone surfaces and regulate bone mass homeostasis","volume":"212","author":"Nevius","year":"2015","journal-title":"J. Exp. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2978","DOI":"10.1002\/1873-3468.12702","article-title":"Liver X receptors link lipid metabolism and inflammation","volume":"591","author":"Schulman","year":"2017","journal-title":"FEBS Lett."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1172\/JCI27883","article-title":"Liver X receptors as integrators of metabolic and inflammatory signaling","volume":"116","author":"Zelcer","year":"2006","journal-title":"J. Clin. Investig."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1359\/jbmr.060503","article-title":"Cholesterol-sensing receptors, liver X receptor alpha and beta, have novel and distinct roles in osteoclast differentiation and activation","volume":"21","author":"Robertson","year":"2006","journal-title":"J. Bone Miner. Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"11019","DOI":"10.1074\/jbc.M111041200","article-title":"Direct and indirect mechanisms for regulation of fatty acid synthase gene expression by liver X receptors","volume":"277","author":"Joseph","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1189\/jlb.1112601","article-title":"Liver X receptor activation inhibits osteoclastogenesis by suppressing NF-kappaB activity and c-Fos induction and prevents inflammatory bone loss in mice","volume":"94","author":"Kim","year":"2013","journal-title":"J. Leukoc. Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"33084","DOI":"10.1074\/jbc.M111.235937","article-title":"Activation of liver X receptor (LXR) inhibits receptor activator of nuclear factor kappaB ligand (RANKL)-induced osteoclast differentiation in an LXRbeta-dependent mechanism","volume":"286","author":"Remen","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.coph.2020.05.001","article-title":"Integrating the roles of liver X receptors in inflammation and infection: Mechanisms and outcomes","volume":"53","author":"Letelier","year":"2020","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1172\/JCI77186","article-title":"Retinoid X receptors orchestrate osteoclast differentiation and postnatal bone remodeling","volume":"125","author":"Roszer","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"3253","DOI":"10.1182\/blood-2006-09-048249","article-title":"MafB negatively regulates RANKL-mediated osteoclast differentiation","volume":"109","author":"Kim","year":"2007","journal-title":"Blood"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"e92704","DOI":"10.1172\/jci.insight.92704","article-title":"Fatty acid oxidation by the osteoblast is required for normal bone acquisition in a sex- and diet-dependent manner","volume":"2","author":"Kim","year":"2017","journal-title":"JCI Insight"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1042\/BST0340223","article-title":"Regulation of acetyl-CoA carboxylase","volume":"34","author":"Brownsey","year":"2006","journal-title":"Biochem. Soc. Trans."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1126\/science.1161269","article-title":"The crystal structure of a mammalian fatty acid synthase","volume":"321","author":"Maier","year":"2008","journal-title":"Science"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1042\/bst0301091","article-title":"Sterol regulatory element-binding proteins: Transcriptional activators of lipid synthesis","volume":"30","author":"Horton","year":"2002","journal-title":"Biochem. Soc. Trans."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1038\/nrc.2016.89","article-title":"The multifaceted roles of fatty acid synthesis in cancer","volume":"16","author":"Rohrig","year":"2016","journal-title":"Nat. Rev. Cancer"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1038\/nrc3483","article-title":"Cancer metabolism: Fatty acid oxidation in the limelight","volume":"13","author":"Carracedo","year":"2013","journal-title":"Nat. Rev. Cancer"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"e12735","DOI":"10.1111\/cpr.12735","article-title":"Therapeutic potentials and modulatory mechanisms of fatty acids in bone","volume":"53","author":"Bao","year":"2020","journal-title":"Cell Prolif."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.plefa.2009.01.004","article-title":"\u03b1-Linolenic acid supplementation and conversion to n-3 long-chain polyunsaturated fatty acids in humans","volume":"80","author":"Brenna","year":"2009","journal-title":"Prostaglandins Leukot. Essent. Fat. Acids"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1079\/BJN2002662","article-title":"Eicosapentaenoic and docosapentaenoic acids are the principal products of alpha-linolenic acid metabolism in young men","volume":"88","author":"Burdge","year":"2002","journal-title":"Br. J. Nutr."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1079\/BJN2002689","article-title":"Conversion of alpha-linolenic acid to eicosapentaenoic, docosapentaenoic and docosahexaenoic acids in young women","volume":"88","author":"Burdge","year":"2002","journal-title":"Br. J. Nutr."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1093\/ajcn\/64.4.577","article-title":"Retroconversion and metabolism of [13C]22:6n-3 in humans and rats after intake of a single dose of [13C]22:6n-3-triacylglycerols","volume":"64","author":"Brossard","year":"1996","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"285S","DOI":"10.1093\/ajcn\/71.1.285S","article-title":"Long-chain polyunsaturated fatty acids, pregnancy, and pregnancy outcome","volume":"71","author":"Al","year":"2000","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1007\/s11914-013-0149-0","article-title":"Polyunsaturated fatty acids and their relation with bone and muscle health in adults","volume":"11","author":"Mangano","year":"2013","journal-title":"Curr. Osteoporos. Rep."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Kasonga, A.E., Deepak, V., Kruger, M.C., and Coetzee, M. (2015). Arachidonic acid and docosahexaenoic acid suppress osteoclast formation and activity in human CD14+ monocytes, in vitro. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0125145"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1359\/jbmr.2003.18.7.1206","article-title":"Dietary n-3 fatty acids decrease osteoclastogenesis and loss of bone mass in ovariectomized mice","volume":"18","author":"Sun","year":"2003","journal-title":"J. Bone Miner. Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/j.cellsig.2016.11.007","article-title":"Docosahexaenoic acid signaling attenuates the proliferation and differentiation of bone marrow-derived osteoclast precursors and promotes apoptosis in mature osteoclasts","volume":"29","author":"Kim","year":"2017","journal-title":"Cell. Signal."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"2584","DOI":"10.3390\/nu6072584","article-title":"Effects of omega3- and omega6-polyunsaturated fatty acids on RANKL-induced osteoclast differentiation of RAW264.7 cells: A comparative in vitro study","volume":"6","author":"Boeyens","year":"2014","journal-title":"Nutrients"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1017\/S0007114510004861","article-title":"Supplementation with a low-moderate dose of n-3 long-chain PUFA has no short-term effect on bone resorption in human adults","volume":"105","author":"Appleton","year":"2011","journal-title":"Br. J. Nutr."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Lavado-Garcia, J., Roncero-Martin, R., Moran, J.M., Pedrera-Canal, M., Aliaga, I., Leal-Hernandez, O., Rico-Martin, S., and Canal-Macias, M.L. (2018). Long-chain omega-3 polyunsaturated fatty acid dietary intake is positively associated with bone mineral density in normal and osteopenic Spanish women. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0190539"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"157","DOI":"10.3389\/fendo.2019.00157","article-title":"Docosahexaenoic Acid Inhibits Inflammation-Induced Osteoclast Formation and Bone Resorption in vivo Through GPR120 by Inhibiting TNF-alpha Production in Macrophages and Directly Inhibiting Osteoclast Formation","volume":"10","author":"Kishikawa","year":"2019","journal-title":"Front. Endocrinol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1016\/j.joen.2017.01.006","article-title":"Omega 3 Fatty Acids Reduce Bone Resorption While Promoting Bone Generation in Rat Apical Periodontitis","volume":"43","author":"Azuma","year":"2017","journal-title":"J. Endod."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"2455","DOI":"10.1210\/en.2011-1917","article-title":"Perinatal maternal dietary supplementation of omega3-fatty acids transiently affects bone marrow microenvironment, osteoblast and osteoclast formation, and bone mass in male offspring","volume":"153","author":"Fong","year":"2012","journal-title":"Endocrinology"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"5688","DOI":"10.1210\/en.2008-0111","article-title":"Modulation of osteoclastogenesis by fatty acids","volume":"149","author":"Cornish","year":"2008","journal-title":"Endocrinology"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"6542","DOI":"10.1074\/jbc.M112.429084","article-title":"The free fatty acid receptor G protein-coupled receptor 40 (GPR40) protects from bone loss through inhibition of osteoclast differentiation","volume":"288","author":"Wauquier","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1002\/jcp.25133","article-title":"G Protein-Coupled Receptor 120 Signaling Negatively Regulates Osteoclast Differentiation, Survival, and Function","volume":"231","author":"Kim","year":"2016","journal-title":"J. Cell. Physiol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"3035","DOI":"10.1016\/j.yexcr.2013.08.013","article-title":"GW9508, a free fatty acid receptor agonist, specifically induces cell death in bone resorbing precursor cells through increased oxidative stress from mitochondrial origin","volume":"319","author":"Philippe","year":"2013","journal-title":"Exp. Cell Res."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1619","DOI":"10.1002\/jbmr.5650111105","article-title":"Leukotriene B4 stimulates osteoclastic bone resorption both in vitro and in vivo","volume":"11","author":"Garcia","year":"1996","journal-title":"J. Bone Miner. Res."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Kasonga, A., Kruger, M.C., and Coetzee, M. (2019). Activation of PPARs Modulates Signalling Pathways and Expression of Regulatory Genes in Osteoclasts Derived from Human CD14+ Monocytes. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20071798"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1016\/j.plipres.2010.06.002","article-title":"Long-chain polyunsaturated fatty acids: Selected mechanisms of action on bone","volume":"49","author":"Kruger","year":"2010","journal-title":"Prog. Lipid Res."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1194\/jlr.M800626-JLR200","article-title":"Saturated fatty acids enhance osteoclast survival","volume":"51","author":"Oh","year":"2010","journal-title":"J. Lipid Res."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1002\/jbmr.2150","article-title":"Palmitic acid and DGAT1 deficiency enhance osteoclastogenesis, while oleic acid-induced triglyceride formation prevents it","volume":"29","author":"Drosatos","year":"2014","journal-title":"J. Bone Miner. Res."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"van Heerden, B., Kasonga, A., Kruger, M.C., and Coetzee, M. (2017). Palmitoleic Acid Inhibits RANKL-Induced Osteoclastogenesis and Bone Resorption by Suppressing NF-kappaB and MAPK Signalling Pathways. Nutrients, 9.","DOI":"10.3390\/nu9050441"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"2049","DOI":"10.1172\/JCI86062","article-title":"Sex steroid deficiency-associated bone loss is microbiota dependent and prevented by probiotics","volume":"126","author":"Li","year":"2016","journal-title":"J. Clin. Investig."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"e73","DOI":"10.1038\/cti.2016.17","article-title":"Regulation of immune cell function by short-chain fatty acids","volume":"5","author":"Fachi","year":"2016","journal-title":"Clin. Transl. Immunol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1038\/s41467-017-02490-4","article-title":"Short-chain fatty acids regulate systemic bone mass and protect from pathological bone loss","volume":"9","author":"Lucas","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.ejphar.2015.10.053","article-title":"Myristoleic acid inhibits osteoclast formation and bone resorption by suppressing the RANKL activation of Src and Pyk2","volume":"768","author":"Kwon","year":"2015","journal-title":"Eur. J. Pharm."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1016\/S0140-6736(72)92571-8","article-title":"Type-IV hyperlipoproteinaemia and transient osteoporosis","volume":"2","author":"Pinals","year":"1972","journal-title":"Lancet"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/s00223-002-2070-x","article-title":"Low bone mineral density in the hip as a marker of advanced atherosclerosis in elderly women","volume":"73","author":"Tanko","year":"2003","journal-title":"Calcif. Tissue Int."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1507\/endocrj.49.211","article-title":"Plasma lipids and osteoporosis in postmenopausal women","volume":"49","author":"Yamaguchi","year":"2002","journal-title":"Endocr. J."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1038\/s41574-019-0170-1","article-title":"Combating osteoporosis and obesity with exercise: Leveraging cell mechanosensitivity","volume":"15","author":"Pagnotti","year":"2019","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1640","DOI":"10.1210\/jc.2006-0572","article-title":"Relationship of obesity with osteoporosis","volume":"92","author":"Zhao","year":"2007","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_106","first-page":"4603","article-title":"Hypercholesterolaemia increases the risk of highturnover osteoporosis in men","volume":"19","author":"Zhou","year":"2019","journal-title":"Mol. Med. Rep."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1093\/ajcn\/83.1.146","article-title":"Relation of body composition, fat mass, and serum lipids to osteoporotic fractures and bone mineral density in Chinese men and women","volume":"83","author":"Hsu","year":"2006","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1007\/s00198-008-0574-6","article-title":"Effects of estrogen therapy on bone marrow adipocytes in postmenopausal osteoporotic women","volume":"19","author":"Syed","year":"2008","journal-title":"Osteoporos. Int."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1306","DOI":"10.1002\/jcb.24470","article-title":"ERalpha regulates lipid metabolism in bone through ATGL and perilipin","volume":"114","author":"Wend","year":"2013","journal-title":"J. Cell. Biochem."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1218","DOI":"10.3390\/nu5041218","article-title":"Dyslipidemia in obesity: Mechanisms and potential targets","volume":"5","author":"Klop","year":"2013","journal-title":"Nutrients"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"433S","DOI":"10.1093\/ajcn\/63.3.433","article-title":"Putting body weight and osteoporosis into perspective","volume":"63","author":"Wardlaw","year":"1996","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1111\/j.1753-4887.2004.tb00019.x","article-title":"Caloric restriction and calcium\u2019s effect on bone metabolism and body composition in overweight and obese premenopausal women","volume":"62","author":"Radak","year":"2004","journal-title":"Nutr. Rev."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"269","DOI":"10.3389\/fendo.2019.00269","article-title":"Mechanisms Involved in Childhood Obesity-Related Bone Fragility","volume":"10","author":"Faienza","year":"2019","journal-title":"Front. Endocrinol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1016\/j.bone.2008.07.245","article-title":"A longitudinal study of the relationship of physical activity to bone mineral accrual from adolescence to young adulthood","volume":"43","author":"Kontulainen","year":"2008","journal-title":"Bone"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1038\/ejcn.2011.104","article-title":"Long-term effect of exercise on bone mineral density and body composition in post-menopausal ex-elite athletes: A retrospective study","volume":"66","author":"Andreoli","year":"2012","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1093\/ajhp\/60.9.883","article-title":"Current approaches to the prevention and treatment of postmenopausal osteoporosis","volume":"60","author":"Follin","year":"2003","journal-title":"Am. J. Health Syst. Pharm."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1002\/jbmr.5650110618","article-title":"Relationship between body composition and bone mass in women","volume":"11","author":"Khosla","year":"1996","journal-title":"J. Bone Miner. Res."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1089\/biores.2018.0025","article-title":"Lean Body Mass in the Prediction of Bone Mineral Density in Postmenopausal Women","volume":"7","author":"Coad","year":"2018","journal-title":"BioRes. Open Access"},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Bierhals, I.O., Dos Santos Vaz, J., Bielemann, R.M., de Mola, C.L., Barros, F.C., Goncalves, H., Wehrmeister, F.C., and Assuncao, M.C.F. (2019). Associations between body mass index, body composition and bone density in young adults: Findings from a southern Brazilian cohort. BMC Musculoskelet. Disord., 20.","DOI":"10.1186\/s12891-019-2656-3"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/s40842-018-0060-9","article-title":"Diabetes mellitus and bone health: Epidemiology, etiology and implications for fracture risk stratification","volume":"4","author":"Valderrabano","year":"2018","journal-title":"Clin. Diabetes Endocrinol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1007\/s11745-014-3950-3","article-title":"High dietary cholesterol masks type 2 diabetes-induced osteopenia and changes in bone microstructure in rats","volume":"49","author":"Lapmanee","year":"2014","journal-title":"Lipids"},{"key":"ref_122","first-page":"1","article-title":"Low Bone Mass is Associated with Increased Carotid Intima Media Thickness in Men with Type 2 Diabetes Mellitus","volume":"6","author":"Bandeira","year":"2013","journal-title":"Clin. Med. Insights Endocrinol. Diabetes"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1007\/s00198-006-0253-4","article-title":"Discrepancies in bone mineral density and fracture risk in patients with type 1 and type 2 diabetes\u2014A meta-analysis","volume":"18","author":"Vestergaard","year":"2007","journal-title":"Osteoporos. Int."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1093\/aje\/kwm106","article-title":"Systematic review of type 1 and type 2 diabetes mellitus and risk of fracture","volume":"166","author":"Janghorbani","year":"2007","journal-title":"Am. J. Epidemiol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1111\/dme.12734","article-title":"Type 1 diabetes and risk of fracture: Meta-analysis and review of the literature","volume":"32","author":"Shah","year":"2015","journal-title":"Diabet. Med."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1007\/s00198-015-3279-7","article-title":"Diabetes mellitus and risk of hip fractures: A meta-analysis","volume":"27","author":"Fan","year":"2016","journal-title":"Osteoporos. Int."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"e024067","DOI":"10.1136\/bmjopen-2018-024067","article-title":"Diabetes mellitus and the risk of fractures at specific sites: A meta-analysis","volume":"9","author":"Wang","year":"2019","journal-title":"BMJ Open"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"6367402","DOI":"10.1155\/2019\/6367402","article-title":"Contribution of Statins towards Periodontal Treatment: A Review","volume":"2019","author":"Petit","year":"2019","journal-title":"Mediat. Inflamm."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1111\/j.1601-0825.2011.01880.x","article-title":"Proinflammatory cytokine levels in hyperlipidemic patients with periodontitis after periodontal treatment","volume":"18","author":"Fentoglu","year":"2012","journal-title":"Oral Dis."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1111\/odi.12002","article-title":"Hyperglycemia induced and intrinsic alterations in type 2 diabetes-derived osteoclast function","volume":"19","author":"Catalfamo","year":"2013","journal-title":"Oral Dis."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1038\/343425a0","article-title":"Regulation of the mevalonate pathway","volume":"343","author":"Goldstein","year":"1990","journal-title":"Nature"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"2583","DOI":"10.1517\/14656566.5.12.2583","article-title":"Simvastatin: A review","volume":"5","author":"Pedersen","year":"2004","journal-title":"Expert Opin. Pharm."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1210\/jc.2018-02054","article-title":"Association Between Cortical Bone Microstructure and Statin Use in Older Women","volume":"104","author":"Larsson","year":"2019","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"2007","DOI":"10.1001\/archinte.165.17.2007","article-title":"Statin use and fracture risk: Study of a US veterans population","volume":"165","author":"Scranton","year":"2005","journal-title":"Arch. Intern. Med."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"2185","DOI":"10.1016\/S0140-6736(00)02400-4","article-title":"Inhibitors of hydroxymethylglutaryl-coenzyme A reductase and risk of fracture among older women","volume":"355","author":"Chan","year":"2000","journal-title":"Lancet"},{"key":"ref_136","first-page":"31","article-title":"Statins and Bone Health: A Mini Review","volume":"14","author":"Morse","year":"2018","journal-title":"Actual. Osteol."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1007\/s00198-002-1323-x","article-title":"HMG CoA reductase inhibitors and the skeleton: A comprehensive review","volume":"14","author":"Bauer","year":"2003","journal-title":"Osteoporos. Int."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"1224","DOI":"10.1002\/jbmr.3989","article-title":"The Effect of Plasma Lipids and Lipid-Lowering Interventions on Bone Mineral Density: A Mendelian Randomization Study","volume":"35","author":"Zheng","year":"2020","journal-title":"J. Bone Miner. Res."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"1946","DOI":"10.1126\/science.286.5446.1946","article-title":"Stimulation of bone formation in vitro and in rodents by statins","volume":"286","author":"Mundy","year":"1999","journal-title":"Science"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1006\/bbrc.2001.5597","article-title":"Pitavastatin enhanced BMP-2 and osteocalcin expression by inhibition of Rho-associated kinase in human osteoblasts","volume":"287","author":"Ohnaka","year":"2001","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"1244","DOI":"10.1002\/jcb.20598","article-title":"Atorvastatin stimulates the production of osteoprotegerin by human osteoblasts","volume":"96","author":"Viereck","year":"2005","journal-title":"J. Cell. Biochem."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1359\/jbmr.2003.18.1.88","article-title":"The ability of statins to inhibit bone resorption is directly related to their inhibitory effect on HMG-CoA reductase activity","volume":"18","author":"Staal","year":"2003","journal-title":"J. Bone Miner. Res."},{"key":"ref_143","doi-asserted-by":"crossref","unstructured":"Nakashima, Y., and Haneji, T. (2013). Stimulation of osteoclast formation by RANKL requires interferon regulatory factor-4 and is inhibited by simvastatin in a mouse model of bone loss. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0072033"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1016\/j.bone.2003.12.014","article-title":"Simvastatin treatment partially prevents ovariectomy-induced bone loss while increasing cortical bone formation","volume":"34","author":"Oxlund","year":"2004","journal-title":"Bone"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1038\/nrd1112","article-title":"Lovastatin and beyond: The history of the HMG-CoA reductase inhibitors","volume":"2","author":"Tobert","year":"2003","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_146","first-page":"53","article-title":"Regulation of osteoclast differentiation by statins","volume":"3","author":"Grasser","year":"2003","journal-title":"J. Musculoskelet. Neuronal Interact."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"2218","DOI":"10.1016\/S0140-6736(00)02408-9","article-title":"Oral statins and increased bone-mineral density in postmenopausal women","volume":"355","author":"Edwards","year":"2000","journal-title":"Lancet"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1016\/j.metabol.2004.01.010","article-title":"Simvastatin increases bone mineral density in hypercholesterolemic postmenopausal women","volume":"53","author":"Lupattelli","year":"2004","journal-title":"Metabolism"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1016\/j.bone.2009.12.023","article-title":"Effects of statins vs. non-statin lipid-lowering therapy on bone formation and bone mineral density biomarkers in patients with hyperlipidemia","volume":"46","author":"Chuengsamarn","year":"2010","journal-title":"Bone"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1007\/s00592-007-0246-6","article-title":"Lovastatin effects on bone mineral density in postmenopausal women with type 2 diabetes mellitus","volume":"44","author":"Safaei","year":"2007","journal-title":"Acta Diabetol."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"114","DOI":"10.4158\/EP.13.2.114","article-title":"Effect of simvastatin use on bone mineral density in women with type 2 diabetes","volume":"13","author":"Uysal","year":"2007","journal-title":"Endocr. Pract."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1007\/s10557-009-6181-8","article-title":"Increased levels of 25 hydroxyvitamin D and 1,25-dihydroxyvitamin D after rosuvastatin treatment: A novel pleiotropic effect of statins?","volume":"23","author":"Yavuz","year":"2009","journal-title":"Cardiovasc. Drugs Ther."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1111\/j.1464-5491.2004.01292.x","article-title":"HMG-CoA reductase inhibitors prevent bone loss in patients with Type 2 diabetes mellitus","volume":"21","author":"Nakashima","year":"2004","journal-title":"Diabet. Med. J. Br. Diabet. Assoc."},{"key":"ref_154","first-page":"1137","article-title":"HMG-CoA reductase inhibitors increase BMD in type 2 diabetes mellitus patients","volume":"85","author":"Chung","year":"2000","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"1869","DOI":"10.2169\/internalmedicine.48.2645","article-title":"Rosuvastatin increased serum osteocalcin levels independent of its serum cholesterol-lowering effect in patients with type 2 diabetes and hypercholesterolemia","volume":"48","author":"Kanazawa","year":"2009","journal-title":"Intern. Med."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"8481735","DOI":"10.1155\/2018\/8481735","article-title":"Effects of Systemic Simvastatin on the Concentrations of Visfatin, Tumor Necrosis Factor-alpha, and Interleukin-6 in Gingival Crevicular Fluid in Patients with Type 2 Diabetes and Chronic Periodontitis","volume":"2018","author":"Bahammam","year":"2018","journal-title":"J. Immunol. Res."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"e12213","DOI":"10.1111\/jicd.12213","article-title":"Subgingivally delivered 1.2% atorvastatin in the treatment of chronic periodontitis among smokers: A randomized, controlled clinical trial","volume":"8","author":"Kumari","year":"2017","journal-title":"J. Investig. Clin. Dent."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1902\/jop.2016.150706","article-title":"1.2% Rosuvastatin Versus 1.2% Atorvastatin Gel Local Drug Delivery and Redelivery in Treatment of Intrabony Defects in Chronic Periodontitis: A Randomized Placebo-Controlled Clinical Trial","volume":"87","author":"Pradeep","year":"2016","journal-title":"J. Periodontol."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1016\/j.bone.2004.05.001","article-title":"The effect of atorvastatin on markers of bone turnover in patients with type 2 diabetes","volume":"35","author":"Braatvedt","year":"2004","journal-title":"Bone"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1359\/jbmr.040209","article-title":"Effects of simvastatin on bone turnover and BMD: A 1-year randomized controlled trial in postmenopausal osteopenic women","volume":"19","author":"Rejnmark","year":"2004","journal-title":"J. Bone Miner. Res."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1007\/s00198-004-1598-1","article-title":"Age-dependent effects of atorvastatin on biochemical bone turnover markers: A randomized controlled trial in postmenopausal women","volume":"15","author":"Berthold","year":"2004","journal-title":"Osteoporos. Int."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1007\/s00281-019-00757-0","article-title":"Metabolic reprogramming in osteoclasts","volume":"41","year":"2019","journal-title":"Semin. Immunopathol."},{"key":"ref_163","doi-asserted-by":"crossref","unstructured":"De Castro-Oros, I., Sola, R., Valls, R.M., Brea, A., Mozas, P., Puzo, J., and Pocovi, M. (2016). Genetic Variants of LDLR and PCSK9 Associated with Variations in Response to Antihypercholesterolemic Effects of Armolipid Plus with Berberine. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0150785"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"1543","DOI":"10.2147\/DMSO.S219013","article-title":"Therapeutic targets of hypercholesterolemia: HMGCR and LDLR","volume":"12","author":"Ma","year":"2019","journal-title":"Diabetes Metab. Syndr. Obes."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"e309","DOI":"10.1016\/S2352-3026(19)30284-4","article-title":"Enasidenib in patients with mutant IDH2 myelodysplastic syndromes: A phase 1 subgroup analysis of the multicentre, AG221-C-001 trial","volume":"7","author":"Stein","year":"2020","journal-title":"Lancet Haematol."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/1\/89\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:08:05Z","timestamp":1760159285000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/1\/89"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,7]]},"references-count":165,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,1]]}},"alternative-id":["cells10010089"],"URL":"https:\/\/doi.org\/10.3390\/cells10010089","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,7]]}}}