{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T03:17:05Z","timestamp":1791429425544,"version":"4.3.3"},"reference-count":159,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,4,16]],"date-time":"2021-04-16T00:00:00Z","timestamp":1618531200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003042","name":"Else Kr\u00f6ner-Fresenius-Stiftung","doi-asserted-by":"publisher","award":["EKFS 2017_A22"],"award-info":[{"award-number":["EKFS 2017_A22"]}],"id":[{"id":"10.13039\/501100003042","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["DFG KE 2179\/2-1"],"award-info":[{"award-number":["DFG KE 2179\/2-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Bone tissue in vertebrates is essential to performing movements, to protecting internal organs and to regulating calcium homeostasis. Moreover, bone has also been suggested to contribute to whole-body physiology as an endocrine organ, affecting male fertility; brain development and cognition; and glucose metabolism. A main determinant of bone quality is the constant remodeling carried out by osteoblasts and osteoclasts, a process consuming vast amounts of energy. In turn, clinical conditions associated with impaired glucose metabolism, including type I and type II diabetes and anorexia nervosa, are associated with impaired bone turnover. As osteoblasts are required for collagen synthesis and matrix mineralization, they represent one of the most important targets for pharmacological augmentation of bone mass. To fulfill their function, osteoblasts primarily utilize glucose through aerobic glycolysis, a process which is regulated by various molecular switches and generates adenosine triphosphate rapidly. In this regard, researchers have been investigating the complex processes of energy utilization in osteoblasts in recent years, not only to improve bone turnover in metabolic disease, but also to identify novel treatment options for primary bone diseases. This review focuses on the metabolism of glucose in osteoblasts in physiological and pathophysiological conditions.<\/jats:p>","DOI":"10.3390\/ijms22084120","type":"journal-article","created":{"date-parts":[[2021,4,16]],"date-time":"2021-04-16T10:20:11Z","timestamp":1618568411000},"page":"4120","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Glucose Metabolism in Osteoblasts in Healthy and Pathophysiological Conditions"],"prefix":"10.3390","volume":"22","author":[{"given":"Antonia","family":"Donat","sequence":"first","affiliation":[{"name":"Department of Trauma and Orthopedic Surgery, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul-Richard","family":"Knapstein","sequence":"additional","affiliation":[{"name":"Department of Trauma and Orthopedic Surgery, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Trauma and Orthopedic Surgery, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anke","family":"Baranowsky","sequence":"additional","affiliation":[{"name":"Department of Trauma and Orthopedic Surgery, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2297-7819","authenticated-orcid":false,"given":"Tobias-Malte","family":"Ballhause","sequence":"additional","affiliation":[{"name":"Department of Trauma and Orthopedic Surgery, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl-Heinz","family":"Frosch","sequence":"additional","affiliation":[{"name":"Department of Trauma and Orthopedic Surgery, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8925-7288","authenticated-orcid":false,"given":"Johannes","family":"Keller","sequence":"additional","affiliation":[{"name":"Department of Trauma and Orthopedic Surgery, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1016\/j.cell.2007.05.047","article-title":"Endocrine regulation of energy metabolism by the skeleton","volume":"130","author":"Lee","year":"2007","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/j.cell.2010.06.003","article-title":"Insulin signaling in osteoblasts integrates bone remodeling and energy metabolism","volume":"142","author":"Ferron","year":"2010","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e12700","DOI":"10.14814\/phy2.12700","article-title":"Glucose-loading reduces bone remodeling in women and osteoblast function in vitro","volume":"4","author":"Levinger","year":"2016","journal-title":"Physiol. Rep."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1007\/s00441-014-1913-x","article-title":"Effects of high glucose and high insulin concentrations on osteoblast function in vitro","volume":"358","author":"Cunha","year":"2014","journal-title":"Cell Tissue Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1007\/s00223-007-9038-9","article-title":"Evaluation of bone loss and its mechanisms in anorexia nervosa","volume":"81","author":"Vignau","year":"2007","journal-title":"Calcif. Tissue Int."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1126\/science.284.5411.143","article-title":"Multilineage potential of adult human mesenchymal stem cells","volume":"284","author":"Pittenger","year":"1999","journal-title":"Science"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1038\/s41586-019-1105-7","article-title":"Developmental origin, functional maintenance and genetic rescue of osteoclasts","volume":"568","author":"Percin","year":"2019","journal-title":"Nature"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1016\/S0092-8674(00)80257-3","article-title":"Osf2\/Cbfa1: A transcriptional activator of osteoblast differentiation","volume":"89","author":"Ducy","year":"1997","journal-title":"Cell"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1016\/S0092-8674(00)80260-3","article-title":"Mutations involving the transcription factor CBFA1 cause cleidocranial dysplasia","volume":"89","author":"Mundlos","year":"1997","journal-title":"Cell"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1016\/S0092-8674(00)80259-7","article-title":"Cbfa1, a candidate gene for cleidocranial dysplasia syndrome, is essential for osteoblast differentiation and bone development","volume":"89","author":"Otto","year":"1997","journal-title":"Cell"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1016\/S0092-8674(00)80258-5","article-title":"Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts","volume":"89","author":"Komori","year":"1997","journal-title":"Cell"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1016\/j.orthres.2004.04.009","article-title":"Distraction osteogenesis in the Cbfa-1+\/- mouse","volume":"22","author":"Isefuku","year":"2004","journal-title":"J. Orthop. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1083\/jcb.200105052","article-title":"Overexpression of Cbfa1 in osteoblasts inhibits osteoblast maturation and causes osteopenia with multiple fractures","volume":"155","author":"Liu","year":"2001","journal-title":"J. Cell Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.gene.2017.05.028","article-title":"Comparative analysis of osteoblast gene expression profiles and Runx2 genomic occupancy of mouse and human osteoblasts in vitro","volume":"626","author":"Tarkkonen","year":"2017","journal-title":"Gene"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/S0092-8674(01)00622-5","article-title":"The novel zinc finger-containing transcription factor osterix is required for osteoblast differentiation and bone formation","volume":"108","author":"Nakashima","year":"2002","journal-title":"Cell"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1002\/dvdy.21836","article-title":"Osterix-mCherry transgenic medaka for in vivo imaging of bone formation","volume":"238","author":"Renn","year":"2009","journal-title":"Dev. Dyn."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1002\/jcp.21176","article-title":"Osterix\/Sp7 regulates mesenchymal stem cell mediated endochondral ossification","volume":"214","author":"Kaback","year":"2008","journal-title":"J. Cell Physiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"12919","DOI":"10.1073\/pnas.0912855107","article-title":"Multiple functions of Osterix are required for bone growth and homeostasis in postnatal mice","volume":"107","author":"Zhou","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1359\/jbmr.081248","article-title":"Positive regulation of adult bone formation by osteoblast-specific transcription factor osterix","volume":"24","author":"Baek","year":"2009","journal-title":"J. Bone Miner. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2839","DOI":"10.1016\/j.bbagen.2012.12.021","article-title":"Nuclear matrix-targeting of the osteogenic factor Runx2 is essential for its recognition and activation of the alkaline phosphatase gene","volume":"1830","author":"Weng","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1002\/jbmr.5650070613","article-title":"Distinct proliferative and differentiated stages of murine MC3T3-E1 cells in culture: An in vitro model of osteoblast development","volume":"7","author":"Quarles","year":"1992","journal-title":"J. Bone Miner. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1879","DOI":"10.1359\/jbmr.2000.15.10.1879","article-title":"Functional characterization of osteoblasts and osteoclasts from alkaline phosphatase knockout mice","volume":"15","author":"Wennberg","year":"2000","journal-title":"J. Bone Miner. Res."},{"key":"ref_23","first-page":"1194","article-title":"Influence of age, sex, and insulin on osteoblast function: Osteoblast dysfunction in diabetes mellitus","volume":"80","author":"Bouillon","year":"1995","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"E64","DOI":"10.1111\/j.1749-6632.2009.04955.x","article-title":"Bone mineral density, osteocalcin, and bone-specific alkaline phosphatase in patients with insulin-dependent diabetes mellitus","volume":"1173","author":"Lumachi","year":"2009","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"7666","DOI":"10.1073\/pnas.85.20.7666","article-title":"A missense mutation in the human liver\/bone\/kidney alkaline phosphatase gene causing a lethal form of hypophosphatasia","volume":"85","author":"Weiss","year":"1988","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.bone.2015.02.022","article-title":"Hypophosphatasia: Validation and expansion of the clinical nosology for children from 25 years experience with 173 pediatric patients","volume":"75","author":"Whyte","year":"2015","journal-title":"Bone"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1210\/er.2018-00126","article-title":"Skeletal and Extraskeletal Actions of Vitamin D: Current Evidence and Outstanding Questions","volume":"40","author":"Bouillon","year":"2019","journal-title":"Endocr. Rev."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"9924","DOI":"10.1073\/pnas.89.20.9924","article-title":"Different missense mutations at the tissue-nonspecific alkaline phosphatase gene locus in autosomal recessively inherited forms of mild and severe hypophosphatasia","volume":"89","author":"Henthorn","year":"1992","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1007\/s00223-020-00771-7","article-title":"Genotype-Phenotype Associations in 72 Adults with Suspected ALPL-Associated Hypophosphatasia","volume":"108","author":"Jandl","year":"2021","journal-title":"Calcif. Tissue Int."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2147","DOI":"10.1007\/s00198-018-4571-0","article-title":"Abnormal bone turnover in individuals with low serum alkaline phosphatase","volume":"29","author":"Tenorio","year":"2018","journal-title":"Osteoporos. Int."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"5215","DOI":"10.1038\/ncomms6215","article-title":"Calcitonin controls bone formation by inhibiting the release of sphingosine 1-phosphate from osteoclasts","volume":"5","author":"Keller","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Kim, J.M., Lin, C., Stavre, Z., Greenblatt, M.B., and Shim, J.H. (2020). Osteoblast-Osteoclast Communication and Bone Homeostasis. Cells, 9.","DOI":"10.3390\/cells9092073"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"25163","DOI":"10.1074\/jbc.M000322200","article-title":"The osteoblast-specific transcription factor Cbfa1 contributes to the expression of osteoprotegerin, a potent inhibitor of osteoclast differentiation and function","volume":"275","author":"Thirunavukkarasu","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_34","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_35","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1093\/jmicro\/51.5.315","article-title":"Osteoprotegerin administration reduces femural bone loss in ovariectomized mice via impairment of osteoclast structure and function","volume":"51","author":"Kawana","year":"2002","journal-title":"J. Electron. Microsc. Tokyo"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4768","DOI":"10.1210\/endo.141.12.7840","article-title":"The expression of osteoprotegerin and RANK ligand and the support of osteoclast formation by stromal-osteoblast lineage cells is developmentally regulated","volume":"141","author":"Gori","year":"2000","journal-title":"Endocrinology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.1038\/ng1905","article-title":"Loss of DMP1 causes rickets and osteomalacia and identifies a role for osteocytes in mineral metabolism","volume":"38","author":"Feng","year":"2006","journal-title":"Nat. Genet."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1007\/s11914-017-0373-0","article-title":"Osteocyte Mechanobiology","volume":"15","author":"Uda","year":"2017","journal-title":"Curr. Osteoporos. Rep."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.colsurfb.2019.03.035","article-title":"Bioactive carbon dots direct the osteogenic differentiation of human bone marrow mesenchymal stem cells","volume":"179","author":"Han","year":"2019","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.bbrc.2019.04.123","article-title":"ATP turnover and glucose dependency in hematopoietic stem\/progenitor cells are increased by proliferation and differentiation","volume":"514","author":"Watanuki","year":"2019","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1576","DOI":"10.1016\/j.cell.2015.05.029","article-title":"Glucose Uptake and Runx2 Synergize to Orchestrate Osteoblast Differentiation and Bone Formation","volume":"161","author":"Wei","year":"2015","journal-title":"Cell"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"4094","DOI":"10.1210\/en.2016-1583","article-title":"Glucose Transporter-4 Facilitates Insulin-Stimulated Glucose Uptake in Osteoblasts","volume":"157","author":"Li","year":"2016","journal-title":"Endocrinology"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"15613","DOI":"10.1073\/pnas.2536196100","article-title":"Glucose transporter-1-deficient mice exhibit impaired development and deformities that are similar to diabetic embryopathy","volume":"100","author":"Heilig","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1038\/377151a0","article-title":"Cardiac and adipose tissue abnormalities but not diabetes in mice deficient in GLUT4","volume":"377","author":"Katz","year":"1995","journal-title":"Nature"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.1002\/jbmr.3390","article-title":"Osteoblast-like MC3T3-E1 Cells Prefer Glycolysis for ATP Production but Adipocyte-like 3T3-L1 Cells Prefer Oxidative Phosphorylation","volume":"33","author":"Guntur","year":"2018","journal-title":"J. Bone Miner. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"108108","DOI":"10.1016\/j.celrep.2020.108108","article-title":"Malic Enzyme Couples Mitochondria with Aerobic Glycolysis in Osteoblasts","volume":"32","author":"Lee","year":"2020","journal-title":"Cell Rep."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1038\/nature13034","article-title":"Direct measurement of local oxygen concentration in the bone marrow of live animals","volume":"508","author":"Spencer","year":"2014","journal-title":"Nature"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Lyons, D.G., Parpaleix, A., Roche, M., and Charpak, S. (2016). Mapping oxygen concentration in the awake mouse brain. Elife, 5.","DOI":"10.7554\/eLife.12024"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.mce.2017.05.017","article-title":"Lactate induces osteoblast differentiation by stabilization of HIF1\u03b1","volume":"452","author":"Wu","year":"2017","journal-title":"Mol. Cell Endocrinol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1172\/JCI97794","article-title":"Vhl deletion in osteoblasts boosts cellular glycolysis and improves global glucose metabolism","volume":"128","author":"Dirckx","year":"2018","journal-title":"J. Clin. Investig."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"8673","DOI":"10.1073\/pnas.1324290111","article-title":"Up-regulation of glycolytic metabolism is required for HIF1\u03b1-driven bone formation","volume":"111","author":"Regan","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.jbiotec.2013.11.010","article-title":"Gas chromatography-mass spectrometry analysis of human mesenchymal stem cell metabolism during proliferation and osteogenic differentiation under different oxygen tensions","volume":"169","author":"Kim","year":"2014","journal-title":"J. Biotechnol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"5432","DOI":"10.1002\/jcp.30249","article-title":"Conditional knockout of the PDK-1 gene in osteoblasts affects osteoblast differentiation and bone formation","volume":"236","author":"Bai","year":"2021","journal-title":"J. Cell Physiol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"40505","DOI":"10.1038\/srep40505","article-title":"A Conditional Knockout Mouse Model Reveals a Critical Role of PKD1 in Osteoblast Differentiation and Bone Development","volume":"7","author":"Li","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1002\/jbmr.4202","article-title":"PDK2 Deficiency Prevents Ovariectomy-Induced Bone Loss in Mice by Regulating the RANKL-NFATc1 Pathway During Osteoclastogenesis","volume":"36","author":"Lee","year":"2021","journal-title":"J. Bone Miner. Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/j.bone.2011.07.012","article-title":"Pyruvate dehydrogenase kinase 4 induces bone loss at unloading by promoting osteoclastogenesis","volume":"50","author":"Wang","year":"2012","journal-title":"Bone"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1146\/annurev.bi.38.070169.005015","article-title":"Oxidative phosphorylation in mitochondria","volume":"38","author":"Lardy","year":"1969","journal-title":"Annu. Rev. Biochem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/S8756-3282(97)00174-9","article-title":"Purinergic transmitters inhibit bone formation by cultured osteoblasts","volume":"21","author":"Jones","year":"1997","journal-title":"Bone"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1126\/science.1160809","article-title":"Understanding the Warburg effect: The metabolic requirements of cell proliferation","volume":"324","author":"Cantley","year":"2009","journal-title":"Science"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1016\/j.cell.2008.08.021","article-title":"Cancer cell metabolism: Warburg and beyond","volume":"134","author":"Hsu","year":"2008","journal-title":"Cell"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2174\/1876525401406010001","article-title":"Evidence that Osteoblasts are Specialized Citrate-producing Cells that Provide the Citrate for Incorporation into the Structure of Bone","volume":"6","author":"Franklin","year":"2014","journal-title":"Open Bone J."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1042\/bj0351011","article-title":"The citric acid content of animal tissues, with reference to its occurrence in bone and tumour","volume":"35","author":"Dickens","year":"1941","journal-title":"Biochem. J."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1002\/jcp.21917","article-title":"Osteoblast differentiation is functionally associated with decreased AMP kinase activity","volume":"221","author":"Kasai","year":"2009","journal-title":"J. Cell Physiol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1016\/j.cmet.2013.03.017","article-title":"WNT-LRP5 signaling induces Warburg effect through mTORC2 activation during osteoblast differentiation","volume":"17","author":"Esen","year":"2013","journal-title":"Cell Metab."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"13028","DOI":"10.1074\/jbc.M115.708578","article-title":"Wnt Protein Signaling Reduces Nuclear Acetyl-CoA Levels to Suppress Gene Expression during Osteoblast Differentiation","volume":"291","author":"Karner","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.1002\/jcb.20284","article-title":"Wnt 3a promotes proliferation and suppresses osteogenic differentiation of adult human mesenchymal stem cells","volume":"93","author":"Boland","year":"2004","journal-title":"J. Cell Biochem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1210\/en.2015-1690","article-title":"IGF-I and IGFBP-2 Stimulate AMPK Activation and Autophagy, Which Are Required for Osteoblast Differentiation","volume":"157","author":"Xi","year":"2016","journal-title":"Endocrinology"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1651","DOI":"10.1002\/jcb.23079","article-title":"TGF-\u03b2 regulates \u03b2-catenin signaling and osteoblast differentiation in human mesenchymal stem cells","volume":"112","author":"Zhou","year":"2011","journal-title":"J. Cell Biochem."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"16019","DOI":"10.1074\/jbc.RA118.004102","article-title":"Active mitochondria support osteogenic differentiation by stimulating \u03b2-catenin acetylation","volume":"293","author":"Shares","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"50259","DOI":"10.1074\/jbc.M307444200","article-title":"Proteasomal degradation of Runx2 shortens parathyroid hormone-induced anti-apoptotic signaling in osteoblasts. A putative explanation for why intermittent administration is needed for bone anabolism","volume":"278","author":"Bellido","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1959","DOI":"10.1002\/jbmr.2556","article-title":"PTH Promotes Bone Anabolism by Stimulating Aerobic Glycolysis via IGF Signaling","volume":"30","author":"Esen","year":"2015","journal-title":"J. Bone Miner. Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2968","DOI":"10.1101\/gad.1702708","article-title":"Parathyroid hormone signaling through low-density lipoprotein-related protein 6","volume":"22","author":"Wan","year":"2008","journal-title":"Genes Dev."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1007\/s11010-010-0634-z","article-title":"Stimulation of glucose transport in osteoblastic cells by parathyroid hormone and insulin-like growth factor I","volume":"348","author":"Zoidis","year":"2011","journal-title":"Mol. Cell Biochem."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1002\/jbmr.5650050406","article-title":"Influence of experimental conditions on osteoblast activity in human primary bone cell cultures","volume":"5","author":"Chavassieux","year":"1990","journal-title":"J. Bone Miner. Res."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Tsao, Y.T., Huang, Y.J., Wu, H.H., Liu, Y.A., Liu, Y.S., and Lee, O.K. (2017). Osteocalcin Mediates Biomineralization during Osteogenic Maturation in Human Mesenchymal Stromal Cells. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18010159"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1111\/j.1440-1681.2010.05463.x","article-title":"Relationship between serum osteocalcin and glycaemic variability in Type 2 diabetes","volume":"38","author":"Bao","year":"2011","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"4807046","DOI":"10.1155\/2017\/4807046","article-title":"Effect of Weight Loss, Exercise, or Both on Undercarboxylated Osteocalcin and Insulin Secretion in Frail, Obese Older Adults","volume":"2017","author":"Colleluori","year":"2017","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Takashi, Y., Ishizu, M., Mori, H., Miyashita, K., Sakamoto, F., Katakami, N., Matsuoka, T.A., Yasuda, T., Hashida, S., and Matsuhisa, M. (2019). Circulating osteocalcin as a bone-derived hormone is inversely correlated with body fat in patients with type 1 diabetes. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0216416"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1337","DOI":"10.1007\/s00198-011-1679-x","article-title":"Circulating osteocalcin level is associated with improved glucose tolerance, insulin secretion and sensitivity independent of the plasma adiponectin level","volume":"23","author":"Hwang","year":"2012","journal-title":"Osteoporos. Int."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1016\/j.molmet.2013.08.004","article-title":"In vivo analysis of the contribution of bone resorption to the control of glucose metabolism in mice","volume":"2","author":"Lacombe","year":"2013","journal-title":"Mol. Metab."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"5266","DOI":"10.1073\/pnas.0711119105","article-title":"Osteocalcin differentially regulates beta cell and adipocyte gene expression and affects the development of metabolic diseases in wild-type mice","volume":"105","author":"Ferron","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.2337\/db13-0887","article-title":"Osteocalcin promotes \u03b2-cell proliferation during development and adulthood through Gprc6a","volume":"63","author":"Wei","year":"2014","journal-title":"Diabetes"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1016\/j.cell.2011.02.004","article-title":"Endocrine regulation of male fertility by the skeleton","volume":"144","author":"Oury","year":"2011","journal-title":"Cell"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1016\/j.cellsig.2014.12.018","article-title":"Signaling pathway for adiponectin expression in adipocytes by osteocalcin","volume":"27","author":"Otani","year":"2015","journal-title":"Cell Signal."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1680","DOI":"10.1002\/jbmr.390","article-title":"GPRC6A mediates responses to osteocalcin in \u03b2-cells in vitro and pancreas in vivo","volume":"26","author":"Pi","year":"2011","journal-title":"J. Bone Miner. Res."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.bone.2014.09.006","article-title":"Oral administration of osteocalcin improves glucose utilization by stimulating glucagon-like peptide-1 secretion","volume":"69","author":"Mizokami","year":"2014","journal-title":"Bone"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1866","DOI":"10.1210\/en.2015-2010","article-title":"Evidence for Osteocalcin Binding and Activation of GPRC6A in \u03b2-Cells","volume":"157","author":"Pi","year":"2016","journal-title":"Endocrinology"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"5995","DOI":"10.1038\/s41598-019-41921-8","article-title":"Metabolic and skeletal homeostasis are maintained in full locus GPRC6A knockout mice","volume":"9","author":"Gasparini","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"2012","DOI":"10.1002\/jbmr.417","article-title":"Genetic evidence points to an osteocalcin-independent influence of osteoblasts on energy metabolism","volume":"26","author":"Yoshikawa","year":"2011","journal-title":"J. Bone Miner. Res."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.bone.2017.01.028","article-title":"Wnt\/\u03b2-catenin signaling in osteoblasts regulates global energy metabolism","volume":"97","author":"Yao","year":"2017","journal-title":"Bone"},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Diegel, C.R., Hann, S., Ayturk, U.M., Hu, J.C.W., Lim, K.E., Droscha, C.J., Madaj, Z.B., Foxa, G.E., Izaguirre, I., and Transgenics Core, V.V.A. (2020). An osteocalcin-deficient mouse strain without endocrine abnormalities. PLoS Genet., 16.","DOI":"10.1371\/journal.pgen.1008361"},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Moriishi, T., Ozasa, R., Ishimoto, T., Nakano, T., Hasegawa, T., Miyazaki, T., Liu, W., Fukuyama, R., Wang, Y., and Komori, H. (2020). Osteocalcin is necessary for the alignment of apatite crystallites, but not glucose metabolism, testosterone synthesis, or muscle mass. PLoS Genet., 16.","DOI":"10.1371\/journal.pgen.1008586"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1007\/s00198-005-0063-0","article-title":"Age-related differences in hormonal and nutritional impact on lean anorexia nervosa bone turnover uncoupling","volume":"17","author":"Galusca","year":"2006","journal-title":"Osteoporos. Int."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/j.clnu.2014.04.016","article-title":"Vitamin K deficiency evaluated by serum levels of undercarboxylated osteocalcin in patients with anorexia nervosa with bone loss","volume":"34","author":"Urano","year":"2015","journal-title":"Clin. Nutr."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/S0006-291X(02)00697-6","article-title":"Leptin prevents the fall in plasma osteocalcin during starvation in male mice","volume":"295","author":"Goldstone","year":"2002","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"115361","DOI":"10.1016\/j.bone.2020.115361","article-title":"Sirtuin 1 deficiency decreases bone mass and increases bone marrow adiposity in a mouse model of chronic energy deficiency","volume":"136","author":"Louvet","year":"2020","journal-title":"Bone"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1097\/MED.0b013e328327728d","article-title":"HbA1c: How do we measure it and what does it mean?","volume":"16","author":"Little","year":"2009","journal-title":"Curr. Opin. Endocrinol. Diabetes Obes."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"3781","DOI":"10.1038\/s41598-017-03748-z","article-title":"Insulin use and Excess Fracture Risk in Patients with Type 2 Diabetes: A Propensity-Matched cohort analysis","volume":"7","author":"Hawley","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"2045","DOI":"10.1002\/jbmr.3826","article-title":"Glycemic Control and Insulin Treatment Alter Fracture Risk in Older Men With Type 2 Diabetes Mellitus","volume":"34","author":"Lee","year":"2019","journal-title":"J. Bone Miner. Res."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1007\/BF00301944","article-title":"Increasing serum osteocalcin after glycemic control in diabetic men","volume":"57","author":"Sayinalp","year":"1995","journal-title":"Calcif. Tissue Int."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1016\/S8756-3282(02)00728-7","article-title":"Effect of feeding on bone turnover markers and its impact on biological variability of measurements","volume":"30","author":"Clowes","year":"2002","journal-title":"Bone"},{"key":"ref_102","first-page":"4603247","article-title":"Chronic Hyperglycemia Modulates Rat Osteoporotic Cortical Bone Microarchitecture into Less Fragile Structures","volume":"2017","author":"Agripino","year":"2017","journal-title":"Int. J. Endocrinol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/S8756-3282(00)00426-9","article-title":"Glucose-induced inhibition of in vitro bone mineralization","volume":"28","author":"Balint","year":"2001","journal-title":"Bone"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/j.bone.2011.10.032","article-title":"High glucose concentrations alter the biomineralization process in human osteoblastic cells","volume":"50","author":"Arzate","year":"2012","journal-title":"Bone"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.diabres.2005.11.010","article-title":"Effects of insulin-like growth factor I on the development of osteoblasts in hyperglycemia","volume":"73","author":"Fang","year":"2006","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1002\/cbin.10779","article-title":"Runx2 alleviates high glucose-suppressed osteogenic differentiation via PI3K\/AKT\/GSK3\u03b2\/\u03b2-catenin pathway","volume":"41","author":"Chen","year":"2017","journal-title":"Cell Biol. Int."},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Gu, H., Song, M., Boonanantanasarn, K., Baek, K., Woo, K.M., Ryoo, H.M., and Baek, J.H. (2018). Conditions Inducing Excessive O-GlcNAcylation Inhibit BMP2-Induced Osteogenic Differentiation of C2C12 Cells. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19010202"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"565","DOI":"10.3892\/ijmm.2016.2457","article-title":"Bradykinin receptors and EphB2\/EphrinB2 pathway in response to high glucose-induced osteoblast dysfunction and hyperglycemia-induced bone deterioration in mice","volume":"37","author":"Wu","year":"2016","journal-title":"Int. J. Mol. Med."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1007\/s11010-020-03732-8","article-title":"Hyperglycemia impairs osteoblast cell migration and chemotaxis due to a decrease in mitochondrial biogenesis","volume":"469","author":"Pahwa","year":"2020","journal-title":"Mol. Cell Biochem."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1002\/1097-4644(20001101)79:2<301::AID-JCB130>3.0.CO;2-0","article-title":"Extracellular glucose influences osteoblast differentiation and c-Jun expression","volume":"79","author":"Zayzafoon","year":"2000","journal-title":"J. Cell Biochem."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1002\/jcb.20842","article-title":"Chronic hyperglycemia modulates osteoblast gene expression through osmotic and non-osmotic pathways","volume":"99","author":"Botolin","year":"2006","journal-title":"J. Cell Biochem."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1897","DOI":"10.1159\/000479605","article-title":"Alpha-Lipoic Acid Alleviates High-Glucose Suppressed Osteogenic Differentiation of MC3T3-E1 Cells via Antioxidant Effect and PI3K\/Akt Signaling Pathway","volume":"42","author":"Dong","year":"2017","journal-title":"Cell Physiol. Biochem."},{"key":"ref_113","first-page":"7249","article-title":"MiR-378 overexpression attenuates high glucose-suppressed osteogenic differentiation through targeting CASP3 and activating PI3K\/Akt signaling pathway","volume":"7","author":"You","year":"2014","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"S35","DOI":"10.1016\/j.bone.2009.02.004","article-title":"Role of oxidative stress in diabetic bone disorder","volume":"45","author":"Hamada","year":"2009","journal-title":"Bone"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/j.bone.2006.09.011","article-title":"Advanced glycation end products stimulate osteoblast apoptosis via the MAP kinase and cytosolic apoptotic pathways","volume":"40","author":"Alikhani","year":"2007","journal-title":"Bone"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1647","DOI":"10.1359\/JBMR.050514","article-title":"Advanced glycation end-products attenuate human mesenchymal stem cells and prevent cognate differentiation into adipose tissue, cartilage, and bone","volume":"20","author":"Kume","year":"2005","journal-title":"J. Bone Miner. Res."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1007\/s11010-007-9557-8","article-title":"Regulation of advanced glycation end product (AGE) receptors and apoptosis by AGEs in osteoblast-like cells","volume":"306","author":"Mercer","year":"2007","journal-title":"Mol. Cell Biochem."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1002\/jbmr.5650110709","article-title":"Role of nonenzymatic glycosylation of type I collagen in diabetic osteopenia","volume":"11","author":"Katayama","year":"1996","journal-title":"J. Bone Miner. Res."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1196\/annals.1433.044","article-title":"Pentosidine effects on human osteoblasts in vitro","volume":"1126","author":"Sanguineti","year":"2008","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1007\/s00223-012-9641-2","article-title":"Advanced glycation end products (AGEs), but not high glucose, inhibit the osteoblastic differentiation of mouse stromal ST2 cells through the suppression of osterix expression, and inhibit cell growth and increasing cell apoptosis","volume":"91","author":"Okazaki","year":"2012","journal-title":"Calcif. Tissue Int."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1502","DOI":"10.2337\/diabetes.52.6.1502","article-title":"A role for advanced glycation end products in diminished bone healing in type 1 diabetes","volume":"52","author":"Santana","year":"2003","journal-title":"Diabetes"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1007\/s12010-015-1925-3","article-title":"AGEs Induce Apoptosis in Rat Osteoblast Cells by Activating the Caspase-3 Signaling Pathway Under a High-Glucose Environment In Vitro","volume":"178","author":"Liu","year":"2016","journal-title":"Appl. Biochem. Biotechnol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1159\/000281826","article-title":"Diabetes induced changes in rat mesenchymal stem cells","volume":"191","author":"Stolzing","year":"2010","journal-title":"Cells Tissues Organs"},{"key":"ref_124","first-page":"650","article-title":"Advanced glycation end products affect growth and function of osteoblasts","volume":"29","author":"Franke","year":"2011","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"1408","DOI":"10.1016\/j.bone.2006.12.057","article-title":"Histomorphometric analysis of diabetic osteopenia in streptozotocin-induced diabetic mice: A possible role of oxidative stress","volume":"40","author":"Hamada","year":"2007","journal-title":"Bone"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"12724","DOI":"10.1038\/srep12724","article-title":"FFA-ROS-P53-mediated mitochondrial apoptosis contributes to reduction of osteoblastogenesis and bone mass in type 2 diabetes mellitus","volume":"5","author":"Li","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"2595","DOI":"10.1002\/jcb.24607","article-title":"Activation of the PI3K\/Akt pathway by oxidative stress mediates high glucose-induced increase of adipogenic differentiation in primary rat osteoblasts","volume":"114","author":"Zhang","year":"2013","journal-title":"J. Cell Biochem."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1038\/nature13270","article-title":"Metformin suppresses gluconeogenesis by inhibiting mitochondrial glycerophosphate dehydrogenase","volume":"510","author":"Madiraju","year":"2014","journal-title":"Nature"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1111\/j.2042-7158.1991.tb06645.x","article-title":"Reconsideration of inhibitory effect of metformin on intestinal glucose absorption","volume":"43","author":"Wilcock","year":"1991","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1111\/dom.12812","article-title":"Metformin reduces the rate of small intestinal glucose absorption in type 2 diabetes","volume":"19","author":"Wu","year":"2017","journal-title":"Diabetes Obes. Metab."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1038\/s41574-019-0242-2","article-title":"Understanding the glucoregulatory mechanisms of metformin in type 2 diabetes mellitus","volume":"15","author":"Foretz","year":"2019","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1055\/s-2007-992786","article-title":"Metformin reverts deleterious effects of advanced glycation end-products (AGEs) on osteoblastic cells","volume":"116","author":"Schurman","year":"2008","journal-title":"Exp. Clin. Endocrinol. Diabetes"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1016\/j.jdiacomp.2009.05.002","article-title":"Metformin reverses the deleterious effects of high glucose on osteoblast function","volume":"24","author":"Zhen","year":"2010","journal-title":"J. Diabetes Complicat."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1055\/s-0030-1267953","article-title":"Effects of metformin and pioglitazone on serum pentosidine levels in type 2 diabetes mellitus","volume":"119","author":"Kanazawa","year":"2011","journal-title":"Exp. Clin. Endocrinol. Diabetes"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1016\/j.jdiacomp.2013.05.006","article-title":"Comparative effects of pioglitazone and metformin on oxidative stress markers in newly diagnosed type 2 diabetes patients: A randomized clinical trial","volume":"27","author":"Mirmiranpour","year":"2013","journal-title":"J. Diabetes Complicat."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.ejphar.2010.02.051","article-title":"Effect of the anti-diabetic drug metformin on bone mass in ovariectomized rats","volume":"635","author":"Gao","year":"2010","journal-title":"Eur. J. Pharmacol."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1007\/s00223-018-0468-3","article-title":"Metformin Alleviates the Bone Loss Induced by Ketogenic Diet: An In Vivo Study in Mice","volume":"104","author":"Liu","year":"2019","journal-title":"Calcif. Tissue Int."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1530\/EJE-20-0507","article-title":"Metformin use is associated with a lower risk of osteoporosis\/vertebral fracture in Taiwanese patients with type 2 diabetes mellitus","volume":"184","author":"Tseng","year":"2020","journal-title":"Eur. J. Endocrinol."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"5682541","DOI":"10.1155\/2016\/5682541","article-title":"Metformin Prevents Nonunion after Three-Cannulated-Screw Fixation in Displaced Femoral Neck Fractures: A Retrospective Study","volume":"2016","author":"Zhu","year":"2016","journal-title":"Biomed. Res. Int."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"1593","DOI":"10.1016\/j.biopha.2018.11.032","article-title":"Metformin; an old antidiabetic drug with new potentials in bone disorders","volume":"109","author":"Bahrambeigi","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1016\/j.stemcr.2016.02.002","article-title":"Activation of GLP-1 Receptor Promotes Bone Marrow Stromal Cell Osteogenic Differentiation through \u03b2-Catenin","volume":"6","author":"Meng","year":"2016","journal-title":"Stem Cell Rep."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"110523","DOI":"10.1016\/j.biopha.2020.110523","article-title":"Liraglutide, a glucagon-like peptide-1 receptor agonist, suppresses osteoclastogenesis through the inhibition of NF-\u03baB and MAPK pathways via GLP-1R","volume":"130","author":"Li","year":"2020","journal-title":"Biomed. Pharmacother."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"51","DOI":"10.3389\/fendo.2019.00051","article-title":"The GLP-1 Receptor Agonist Exenatide Ameliorates Bone Composition and Tissue Material Properties in High Fat Fed Diabetic Mice","volume":"10","author":"Mansur","year":"2019","journal-title":"Front. Endocrinol. Lausanne"},{"key":"ref_144","doi-asserted-by":"crossref","unstructured":"Lu, N., Sun, H., Yu, J., Wang, X., Liu, D., Zhao, L., Sun, L., Zhao, H., Tao, B., and Liu, J. (2015). Glucagon-like peptide-1 receptor agonist Liraglutide has anabolic bone effects in ovariectomized rats without diabetes. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0132744"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"1641","DOI":"10.1002\/jbmr.1898","article-title":"Exendin-4, a glucagon-like peptide-1 receptor agonist, prevents osteopenia by promoting bone formation and suppressing bone resorption in aged ovariectomized rats","volume":"28","author":"Ma","year":"2013","journal-title":"J. Bone Miner. Res."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1007\/s00223-015-9993-5","article-title":"Bone fracture risk is not associated with the use of glucagon-like peptide-1 receptor agonists: A population-based cohort analysis","volume":"97","author":"Driessen","year":"2015","journal-title":"Calcif. Tissue Int."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.cmet.2016.10.007","article-title":"Cellular Sites and Mechanisms Linking Reduction of Dipeptidyl Peptidase-4 Activity to Control of Incretin Hormone Action and Glucose Homeostasis","volume":"25","author":"Mulvihill","year":"2017","journal-title":"Cell Metab."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"109796","DOI":"10.1016\/j.biopha.2019.109796","article-title":"Anagliptin stimulates osteoblastic cell differentiation and mineralization","volume":"129","author":"Dong","year":"2020","journal-title":"Biomed. Pharmacother."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1016\/j.jcjd.2018.01.006","article-title":"Dipeptidyl Peptidase-4 Inhibitor, Vildagliptin, Improves Trabecular Bone Mineral Density and Microstructure in Obese, Insulin-Resistant, Pre-diabetic Rats","volume":"42","author":"Charoenphandhu","year":"2018","journal-title":"Can. J. Diabetes"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1186\/1479-5876-11-271","article-title":"IGF-I increases markers of osteoblastic activity and reduces bone resorption via osteoprotegerin and RANK-ligand","volume":"11","author":"Puche","year":"2013","journal-title":"J. Transl. Med."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"1498","DOI":"10.1038\/aps.2011.135","article-title":"High cholesterol diet increases osteoporosis risk via inhibiting bone formation in rats","volume":"32","author":"You","year":"2011","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"2474","DOI":"10.2337\/dc11-1099","article-title":"Dipeptidyl peptidase-4 inhibitors and bone fractures: A meta-analysis of randomized clinical trials","volume":"34","author":"Monami","year":"2011","journal-title":"Diabetes Care"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"2109","DOI":"10.1002\/jbmr.1961","article-title":"Positive regulation of osteogenesis by bile acid through FXR","volume":"28","author":"Cho","year":"2013","journal-title":"J. Bone Miner. Res."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"e022577","DOI":"10.1136\/bmjopen-2018-022577","article-title":"Comparative safety of the sodium glucose co-transporter 2 (SGLT2) inhibitors: A systematic review and meta-analysis","volume":"9","author":"Donnan","year":"2019","journal-title":"BMJ Open"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"2709","DOI":"10.1007\/s00198-016-3595-6","article-title":"Risk of fractures and diabetes medications: A nationwide cohort study","volume":"27","author":"Choi","year":"2016","journal-title":"Osteoporos. Int."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1038\/nm.4208","article-title":"PPAR-\u03b3 regulates pharmacological but not physiological or pathological osteoclast formation","volume":"22","author":"Zou","year":"2016","journal-title":"Nat. Med."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"1496","DOI":"10.1038\/nm1672","article-title":"PPAR-gamma regulates osteoclastogenesis in mice","volume":"13","author":"Wan","year":"2007","journal-title":"Nat. Med."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1210\/jcem.83.3.4674","article-title":"Bone marker and bone density responses to dopamine agonist therapy in hyperprolactinemic males","volume":"83","author":"Colao","year":"1998","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bone.2013.04.019","article-title":"Dopamine D2-like receptor signaling suppresses human osteoclastogenesis","volume":"56","author":"Hanami","year":"2013","journal-title":"Bone"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/8\/4120\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:48:44Z","timestamp":1760161724000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/8\/4120"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,16]]},"references-count":159,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2021,4]]}},"alternative-id":["ijms22084120"],"URL":"https:\/\/doi.org\/10.3390\/ijms22084120","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,16]]}}}