{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T14:40:30Z","timestamp":1787668830884,"version":"build-2736575974"},"reference-count":165,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T00:00:00Z","timestamp":1779062400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82574899"],"award-info":[{"award-number":["82574899"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"award":["82574899"],"award-info":[{"award-number":["82574899"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007129","name":"Shandong Provincial Natural Science Foundation","doi-asserted-by":"crossref","award":["ZR2024QH088"],"award-info":[{"award-number":["ZR2024QH088"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100020196","name":"Shandong Postdoctoral Science Foundation","doi-asserted-by":"crossref","award":["SDBX202302017"],"award-info":[{"award-number":["SDBX202302017"]}],"id":[{"id":"10.13039\/501100020196","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Shandong University of Traditional Chinese Medicine Science Foundation","award":["KYZK2024Q08"],"award-info":[{"award-number":["KYZK2024Q08"]}]},{"name":"Chronic Disease Management Research Project of the National Health Commission Capacity Building and Continuing Education Center","award":["GWJJMB202510024117"],"award-info":[{"award-number":["GWJJMB202510024117"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Osteoporosis is a systemic skeletal disorder characterized by low bone mass, microarchitectural deterioration, and an increased risk of fracture. Its pathogenesis is closely associated with disturbances in energy metabolism, particularly glucose metabolic reprogramming in bone cells. Under osteoporotic conditions, the balance between osteoblasts and osteoclasts is disrupted, accompanied by impaired oxidative phosphorylation, dysregulated glycolysis, and reduced tricarboxylic acid cycle efficiency, ultimately leading to mitochondrial dysfunction. These metabolic alterations result in an insufficient energy supply and accelerate bone loss. Accordingly, the modulation of key enzymes involved in glucose metabolism has emerged as a promising therapeutic strategy. Strategies include the use of natural compounds, traditional Chinese medicine formulas, and specific inhibitors to modulate glucose metabolism processes and related pathways, thereby restoring cellular energy homeostasis and bone remodeling balance. This review summarizes pharmacological agents regulating glucose metabolism and proposes a hierarchical framework for therapeutic prioritization: first, inhibiting pathological glycolysis in osteoclasts (particularly via LDHA and PKM2). Second, restoring oxidative phosphorylation in osteoblasts (e.g., via COX I\u2013V or ATP synthase). And third, employing multi-target traditional Chinese medicine formulas as complementary strategies. By establishing this cell-type-specific and pathway-specific hierarchy, the review aims to provide a theoretical basis for future research on metabolic interventions in bone diseases.<\/jats:p>","DOI":"10.3390\/ijms27104536","type":"journal-article","created":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T07:35:43Z","timestamp":1779176143000},"page":"4536","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Regulating Glucose Metabolism Enzymes for Osteoporosis Therapy: Current and Future Approaches"],"prefix":"10.3390","volume":"27","author":[{"given":"Ziwen","family":"Zhang","sequence":"first","affiliation":[{"name":"College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250355, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuo","family":"Tian","sequence":"additional","affiliation":[{"name":"College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250355, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Li","sequence":"additional","affiliation":[{"name":"College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250355, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuwei","family":"Du","sequence":"additional","affiliation":[{"name":"Institute of Pharmacy (Institute of TCM Health Industrial Technology), Shandong University of Traditional Chinese Medicine, Jinan 250355, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linhui","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Pharmacy (Institute of TCM Health Industrial Technology), Shandong University of Traditional Chinese Medicine, Jinan 250355, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Pharmacy (Institute of TCM Health Industrial Technology), Shandong University of Traditional Chinese Medicine, Jinan 250355, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Zhao","sequence":"additional","affiliation":[{"name":"Institute of Pharmacy (Institute of TCM Health Industrial Technology), Shandong University of Traditional Chinese Medicine, Jinan 250355, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanqiu","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Pharmacy (Institute of TCM Health Industrial Technology), Shandong University of Traditional Chinese Medicine, Jinan 250355, China"},{"name":"Shandong Key Laboratory of Innovation and Application Research in Basic Theory of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250355, China"},{"name":"Shandong Key Laboratory of Digital Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250355, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1186\/s13018-023-04013-y","article-title":"Sodium butyrate enhances titanium nail osseointegration in ovariectomized rats by inhibiting the PKC\u03b1\/NOX4\/ROS\/NF-\u03baB pathways","volume":"18","author":"Liu","year":"2023","journal-title":"J. Orthop. Surg. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1007\/s11657-020-0706-y","article-title":"Fragility fractures in Europe: Burden, management and opportunities","volume":"15","author":"Karlsson","year":"2020","journal-title":"Arch. Osteoporos."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"171","DOI":"10.5312\/wjo.v7.i3.171","article-title":"Major osteoporotic fragility fractures: Risk factor updates and societal impact","volume":"7","author":"Pisani","year":"2016","journal-title":"World J. Orthop."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1016\/j.ajog.2005.08.047","article-title":"Epidemiology, etiology, and diagnosis of osteoporosis","volume":"194","author":"Lane","year":"2006","journal-title":"Am. J. Obs. Gynecol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1007\/s43465-023-01058-3","article-title":"Classification of osteoporosis","volume":"57","author":"Amarnath","year":"2023","journal-title":"Indian J. Orthop."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"7635","DOI":"10.3390\/ijms12117635","article-title":"A HNMR-based metabonomics study of postmenopausal osteoporosis and intervention effects of Er-Xian Decoction in ovariectomized rats","volume":"12","author":"Xue","year":"2011","journal-title":"Int. J. Mol. Sci."},{"key":"ref_7","first-page":"769","article-title":"Asiatic acid improves high-fat-diet-induced osteoporosis in mice via regulating SIRT1\/FOXO1 signaling and inhibiting oxidative stress","volume":"37","author":"Chen","year":"2022","journal-title":"Histol. Histopathol."},{"key":"ref_8","first-page":"7870","article-title":"Leptin attenuates the osteogenic induction potential of BMP9 by increasing \u03b2-catenin malonylation modification via Sirt5 down-regulation","volume":"16","author":"Ke","year":"2024","journal-title":"Aging"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Zhang, X., Wang, W., Wang, Y., Zhao, H., Han, X., Zhao, T., and Qu, P. (2020). Extracellular vesicle-encapsulated miR-29b-3p released from bone marrow-derived mesenchymal stem cells underpins osteogenic differentiation. Front. Cell Dev. Biol., 8.","DOI":"10.3389\/fcell.2020.581545"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1089\/ten.teb.2016.0454","article-title":"Osteoblast differentiation and bone matrix formation in vivo and in vitro","volume":"23","author":"Blair","year":"2017","journal-title":"Tissue Eng. Part B Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3225","DOI":"10.2337\/db16-0053","article-title":"Regulation of glucose handling by the skeleton: Insights from mouse and human studies","volume":"65","author":"Liu","year":"2016","journal-title":"Diabetes"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1007\/s11914-022-00721-2","article-title":"Bioenergetic metabolism in osteoblast differentiation","volume":"20","author":"Shen","year":"2022","journal-title":"Curr. Osteoporos. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Ye, J., Xiao, J., Wang, J., Ma, Y., Zhang, Y., Zhang, Q., Zhang, Z., and Yin, H. (2021). The interaction between intracellular energy metabolism and signaling pathways during osteogenesis. Front. Mol. Biosci., 8.","DOI":"10.3389\/fmolb.2021.807487"},{"key":"ref_14","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_15","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.bone.2017.08.008","article-title":"Glucose metabolism in bone","volume":"115","author":"Karner","year":"2018","journal-title":"Bone"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e1369","DOI":"10.1002\/ctm2.1369","article-title":"Arginine methylation of PPP1CA by CARM1 regulates glucose metabolism and affects osteogenic differentiation and osteoclastic differentiation","volume":"13","author":"Zhang","year":"2023","journal-title":"Clin. Transl. Med."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Da, W., Tao, L., and Zhu, Y. (2021). The role of osteoclast energy metabolism in the occurrence and development of osteoporosis. Front. Endocrinol., 12.","DOI":"10.3389\/fendo.2021.675385"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"21020","DOI":"10.1038\/s41598-020-77892-4","article-title":"Metabolic reprogramming of osteoclasts represents a therapeutic target during the treatment of osteoporosis","volume":"10","author":"Taubmann","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1007\/s11914-014-0235-y","article-title":"Aerobic glycolysis in osteoblasts","volume":"12","author":"Esen","year":"2014","journal-title":"Curr. Osteoporos. Rep."},{"key":"ref_20","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_21","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1007\/s11914-022-00747-6","article-title":"Glycemic control and bone in diabetes","volume":"20","author":"Weber","year":"2022","journal-title":"Curr. Osteoporos. Rep."},{"key":"ref_22","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_23","doi-asserted-by":"crossref","first-page":"100521","DOI":"10.1016\/j.jbo.2024.100521","article-title":"Reprogramming of glucose metabolism: Metabolic alterations in the progression of osteosarcoma","volume":"44","author":"An","year":"2024","journal-title":"J. Bone Oncol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e13374","DOI":"10.7554\/eLife.13374","article-title":"Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation","volume":"5","author":"Zheng","year":"2016","journal-title":"eLife"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Zhu, L., Zhou, C., Chen, S., Huang, D., Jiang, Y., Lan, Y., Zou, S., and Li, Y. (2022). Osteoporosis and alveolar bone health in periodontitis niche: A predisposing factors-centered review. Cells, 11.","DOI":"10.3390\/cells11213380"},{"key":"ref_26","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_27","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1007\/s00394-017-1498-8","article-title":"Reduced energy availability: Implications for bone health in physically active populations","volume":"57","author":"Papageorgiou","year":"2018","journal-title":"Eur. J. Nutr."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/j.tem.2023.12.009","article-title":"Energy homeostasis in the bone","volume":"35","author":"Zhou","year":"2024","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1650","DOI":"10.1038\/s41418-024-01371-w","article-title":"Foxk1 promotes bone formation through inducing aerobic glycolysis","volume":"31","author":"Liu","year":"2024","journal-title":"Cell Death Differ."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Pellegrini, G.G., Morales, C.C., Wallace, T.C., Plotkin, L.I., and Bellido, T. (2016). Avenanthramides Prevent Osteoblast and Osteocyte Apoptosis and Induce Osteoclast Apoptosis in Vitro in an Nrf2-Independent Manner. Nutrients, 8.","DOI":"10.3390\/nu8070423"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1056\/NEJM199502023320506","article-title":"Bone marrow, cytokines, and bone remodeling. Emerging insights into the pathophysiology of osteoporosis","volume":"332","author":"Manolagas","year":"1995","journal-title":"N. Engl. J. Med."},{"key":"ref_32","first-page":"263","article-title":"Correlation between traditional Chinese medicine evidence and lipid metabolism-regulating kinase in elderly patients with osteoporosis","volume":"30","author":"Gu","year":"2024","journal-title":"Altern. Ther. Health Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.dcmed.2024.09.007","article-title":"Integrative analysis of bone-formation associated genes and immune cell infiltration in osteoporosis, and the prediction of active ingredients in targeted traditional Chinese medicine","volume":"7","author":"Wang","year":"2024","journal-title":"Digit. Chin. Med."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Geng, Z., Yuan, L., See, D., and Zhao, Y. (2025). Characterization of the integrated gut microbiota and metabolite profiles in osteoporosis patients with different traditional Chinese medicine syndromes. Front. Microbiol., 16.","DOI":"10.3389\/fmicb.2025.1663716"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Gao, Y., Patil, S., and Jia, J. (2021). The development of molecular biology of osteoporosis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22158182"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Zhao, W., Hou, Y., Song, X., Wang, L., Zhang, F., Zhang, H., Yu, H., and Zhou, Y. (2021). Estrogen deficiency induces mitochondrial damage prior to emergence of cognitive deficits in a postmenopausal mouse model. Front. Aging Neurosci., 13.","DOI":"10.3389\/fnagi.2021.713819"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Yan, C., Shi, Y., Yuan, L., Lv, D., Sun, B., Wang, J., Liu, X., and An, F. (2023). Mitochondrial quality control and its role in osteoporosis. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1077058"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"767","DOI":"10.14336\/AD.2023.0510","article-title":"Altered Osteoblast Metabolism with Aging Results in Lipid Accumulation and Oxidative Stress Mediated Bone Loss","volume":"15","author":"Nandy","year":"2024","journal-title":"Aging Dis."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Ma, X., and Zhang, X. (2025). Research progress of diabetic osteoporosis: A comprehensive review. Front. Endocrinol., 16.","DOI":"10.3389\/fendo.2025.1595228"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e85714","DOI":"10.7554\/eLife.85714","article-title":"Osteoblast-intrinsic defect in glucose metabolism impairs bone formation in type II diabetic male mice","volume":"12","author":"Song","year":"2023","journal-title":"eLife"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"van der Eerden, B.C.J., Riddle, R.C., Stegen, S., and Tencerova, M. (2023). Editorial: Energy metabolism within the skeleton. Front. Physiol., 14.","DOI":"10.3389\/fphys.2023.1205435"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1002\/jbmr.321","article-title":"The osteoblast: An insulin target cell controlling glucose homeostasis","volume":"26","author":"Clemens","year":"2011","journal-title":"J. Bone Min. Res."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Pang, C.Y., Chen, L.R., and Chen, K.H. (2026). Osteoporosis in Patients with Pre-Existing Diabetes Mellitus and in Women with Estrogen Deficiency: A Molecular and Cellular Perspective. Int. J. Mol. Sci., 27.","DOI":"10.3390\/ijms27031453"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"108439","DOI":"10.1016\/j.jbc.2025.108439","article-title":"PKM2 regulates osteoclastogenesis by affecting osteoclast precursor cell fusion via downregulation of OC-STAMP and DC-STAMP","volume":"301","author":"Cai","year":"2025","journal-title":"J. Biol. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1111\/j.1463-1326.2011.01461.x","article-title":"A randomized, parallel group, double-blind, multicentre study comparing the efficacy and safety of Avandamet (rosiglitazone\/metformin) and metformin on long-term glycaemic control and bone mineral density after 80 weeks of treatment in drug-na\u00efve type 2 diabetes mellitus patients","volume":"13","author":"Borges","year":"2011","journal-title":"Diabetes Obes. Metab."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/j.ccr.2006.04.023","article-title":"Attenuation of LDH-A expression uncovers a link between glycolysis, mitochondrial physiology, and tumor maintenance","volume":"9","author":"Fantin","year":"2006","journal-title":"Cancer Cell"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"141638","DOI":"10.1016\/j.scitotenv.2020.141638","article-title":"Cadmium exposure triggers osteoporosis in duck via P2X7\/PI3K\/AKT-mediated osteoblast and osteoclast differentiation","volume":"750","author":"Ma","year":"2021","journal-title":"Sci. Total Env."},{"key":"ref_48","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_49","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1002\/kjm2.12906","article-title":"Nuciferine inhibits osteoclast formation through suppressing glycolysis metabolic programming and ROS production","volume":"40","author":"Guo","year":"2024","journal-title":"Kaohsiung J. Med. Sci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3976","DOI":"10.18632\/aging.102866","article-title":"PKM2 suppresses osteogenesis and facilitates adipogenesis by regulating \u03b2-catenin signaling and mitochondrial fusion and fission","volume":"12","author":"Guo","year":"2020","journal-title":"Aging"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"0351","DOI":"10.34133\/research.0351","article-title":"The Tricarboxylic Acid Cycle Metabolites for Cancer: Friend or Enemy","volume":"7","author":"Wu","year":"2024","journal-title":"Research"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1016\/j.smim.2016.10.009","article-title":"Metabolic pathways in T cell activation and lineage differentiation","volume":"28","author":"Almeida","year":"2016","journal-title":"Semin. Immunol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2175","DOI":"10.1111\/nph.19989","article-title":"Mitochondrial respiration is essential for photosynthesis-dependent ATP supply of the plant cytosol","volume":"243","author":"Novel","year":"2024","journal-title":"New Phytol."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"\u0150sz, F., Nazir, A., Tak\u00e1cs-Vellai, K., and Farkas, Z. (2025). Mutations of the Electron Transport Chain Affect Lifespan and ROS Levels in C. elegans. Antioxidants, 14.","DOI":"10.3390\/antiox14010076"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1016\/j.sbi.2013.06.013","article-title":"Revealing various coupling of electron transfer and proton pumping in mitochondrial respiratory chain","volume":"23","author":"Sun","year":"2013","journal-title":"Curr. Opin. Struct. Biol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"3070","DOI":"10.1038\/s41598-019-38564-0","article-title":"ATP synthesis at physiological nucleotide concentrations","volume":"9","author":"Meyrat","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"5410","DOI":"10.1038\/s41467-025-61227-w","article-title":"Engineering of ATP synthase for enhancement of proton-to-ATP ratio","volume":"16","author":"Ueno","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1530\/EOR-24-0023","article-title":"Mitochondrial maintenance as a novel target for treating steroid-induced osteonecrosis of femoral head: A narrative review","volume":"9","author":"Yang","year":"2024","journal-title":"EFORT Open Rev."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"e2611","DOI":"10.7717\/peerj.2611","article-title":"Iron overload induced death of osteoblasts in vitro: Involvement of the mitochondrial apoptotic pathway","volume":"4","author":"Tian","year":"2016","journal-title":"PeerJ"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"115368","DOI":"10.1016\/j.bios.2023.115368","article-title":"Photoelectrochemical detection of superoxide anions released from mitochondria in HepG2 cells based on the synergistic effect of MnO2@Co3O4 core-shell p-n heterojunction","volume":"237","author":"Zhao","year":"2023","journal-title":"Biosens. Bioelectron."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"e52727","DOI":"10.15252\/embr.202152727","article-title":"Mitochondrial F1FO ATP synthase determines the local proton motive force at cristae rims","volume":"22","author":"Rieger","year":"2021","journal-title":"EMBO Rep."},{"key":"ref_62","first-page":"5991","article-title":"Reactive Oxygen Species Control Osteoblast Apoptosis through SIRT1\/PGC-1\u03b1\/P53Lys382 Signaling, Mediating the Onset of Cd-Induced Osteoporosis","volume":"71","author":"Ran","year":"2023","journal-title":"J. Agric. Food Chem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2480","DOI":"10.1021\/jf000537w","article-title":"Antioxidant activity of hydroxytyrosol acetate compared with that of other olive oil polyphenols","volume":"49","author":"Gordon","year":"2001","journal-title":"J. Agric. Food Chem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"4101738","DOI":"10.1155\/2019\/4101738","article-title":"AKT-GSK3\u03b2 Signaling Pathway Regulates Mitochondrial Dysfunction-Associated OPA1 Cleavage Contributing to Osteoblast Apoptosis: Preventative Effects of Hydroxytyrosol","volume":"2019","author":"Cai","year":"2019","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"8594","DOI":"10.1039\/D5FO02820E","article-title":"Inhibition of ex vivo VEGF-induced angiogenesis by tyrosol and hydroxytyrosol: A quantitative three-dimensional mouse aortic ring model","volume":"16","author":"Cerezo","year":"2025","journal-title":"Food Funct."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Scoditti, E., Massaro, M., Carluccio, M.A., Pellegrino, M., Wabitsch, M., Calabriso, N., Storelli, C., and De Caterina, R. (2015). Additive regulation of adiponectin expression by the mediterranean diet olive oil components oleic Acid and hydroxytyrosol in human adipocytes. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0128218"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"3268136","DOI":"10.1155\/2021\/3268136","article-title":"Genistein: An Integrative Overview of Its Mode of Action, Pharmacological Properties, and Health Benefits","volume":"2021","author":"Quispe","year":"2021","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1142\/S0192415X21500439","article-title":"Genistein Triggers Translocation of Estrogen Receptor-Alpha in Mitochondria to Induce Expressions of ATP Synthesis-Associated Genes and Improves Energy Production and Osteoblast Maturation","volume":"49","author":"Wu","year":"2021","journal-title":"Am. J. Chin. Med."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1111\/j.1753-4887.2009.00213.x","article-title":"The effect of genistein aglycone on cancer and cancer risk: A review of in vitro, preclinical, and clinical studies","volume":"67","author":"Taylor","year":"2009","journal-title":"Nutr. Rev."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Arcoraci, V., Atteritano, M., Squadrito, F., D\u2019Anna, R., Marini, H., Santoro, D., Minutoli, L., Messina, S., Altavilla, D., and Bitto, A. (2017). Antiosteoporotic Activity of Genistein Aglycone in Postmenopausal Women: Evidence from a Post-Hoc Analysis of a Multicenter Randomized Controlled Trial. Nutrients, 9.","DOI":"10.3390\/nu9020179"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"839","DOI":"10.7326\/0003-4819-146-12-200706190-00005","article-title":"Effects of the phytoestrogen genistein on bone metabolism in osteopenic postmenopausal women: A randomized trial","volume":"146","author":"Marini","year":"2007","journal-title":"Ann. Intern. Med."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1904","DOI":"10.1359\/jbmr.2002.17.10.1904","article-title":"Effects of genistein and hormone-replacement therapy on bone loss in early postmenopausal women: A randomized double-blind placebo-controlled study","volume":"17","author":"Morabito","year":"2002","journal-title":"J. Bone Min. Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"271","DOI":"10.4103\/jehp.jehp_1727_21","article-title":"Osteoporosis risk group: Screening for osteoporosis in dental clinics using panoramic radiographs","volume":"11","author":"Selvakumar","year":"2022","journal-title":"J. Educ. Health Promot."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Yeh, P.S., Chen, J.T., Cherng, Y.G., Yang, S.T., Tai, Y.T., and Chen, R.M. (2020). Methylpiperidinopyrazole Attenuates Estrogen-Induced Mitochondrial Energy Production and Subsequent Osteoblast Maturation via an Estrogen Receptor Alpha-Dependent Mechanism. Molecules, 25.","DOI":"10.3390\/molecules25122876"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1007\/s12192-016-0735-z","article-title":"Protective effect of \u03b1-lipoic acid against antimycin A cytotoxicity in MC3T3-E1 osteoblastic cells","volume":"22","author":"Lin","year":"2017","journal-title":"Cell Stress Chaperones"},{"key":"ref_76","first-page":"8","article-title":"Study on the application value and mechanism of Erxian Decoction in the treatment of postmenopausal osteoporosis with kidney-yang deficiency syndrome","volume":"34","author":"Wang","year":"2022","journal-title":"J. Tradit. Chin. Orthop. Traumatol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"4695","DOI":"10.3390\/molecules15074695","article-title":"Antiosteoporotic effects and proteomic characterization of the target and mechanism of an Er-Xian Decoction on osteoblastic UMR-106 and osteoclasts induced from RAW264.7","volume":"15","author":"Zhu","year":"2010","journal-title":"Molecules"},{"key":"ref_78","first-page":"281","article-title":"Clinical guidelines for the diagnosis and treatment of primary osteoporosis (2017)","volume":"25","author":"Xia","year":"2019","journal-title":"Chin. J. Osteoporos."},{"key":"ref_79","first-page":"1717","article-title":"Expert consensus on prevention and treatment of primary osteoporosis with traditional Chinese medicine (2020)","volume":"26","author":"Ge","year":"2020","journal-title":"Chin. J. Osteoporos."},{"key":"ref_80","first-page":"1118","article-title":"Clinical Observation on Erxian Decoction in the Treatment of Senile Osteoporosis with Kidney-Yang Deficiency Syndrome","volume":"39","author":"Xu","year":"2024","journal-title":"Guangming J. Chin. Med."},{"key":"ref_81","first-page":"851","article-title":"Research progress on the pharmacological effects and clinical applications of Erxian Decoction","volume":"46","author":"Cao","year":"2025","journal-title":"World Clin. Drugs"},{"key":"ref_82","first-page":"704","article-title":"Research progress on the treatment of osteoporosis via the AMPK\/mTOR signaling pathway mediated by traditional Chinese medicine","volume":"54","author":"Zhang","year":"2023","journal-title":"J. New Med."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Marini, H., Polito, F., Adamo, E.B., Bitto, A., Squadrito, F., and Benvenga, S. (2012). Update on genistein and thyroid: An overall message of safety. Front. Endocrinol., 3.","DOI":"10.3389\/fendo.2012.00094"},{"key":"ref_84","unstructured":"Yang, J. (2012). Study on the Mechanism of Zhuanggu Zhitong Formula in Treating Osteoporosis from the Perspective of Proteomics. [Ph.D. Thesis, Hunan University of Chinese Medicine]. (In Chinese)."},{"key":"ref_85","first-page":"16","article-title":"Clinical observation on 50 cases of postmenopausal osteoporosis treated with Zhuanggu Zhitong Formula","volume":"32","author":"Peng","year":"2016","journal-title":"Hunan J. Tradit. Chin. Med."},{"key":"ref_86","first-page":"2087","article-title":"Clinical study on Zhuanggu Zhitong Capsules combined with teriparatide in the treatment of postmenopausal osteoporosis","volume":"37","author":"Yang","year":"2022","journal-title":"Drugs Clin."},{"key":"ref_87","first-page":"2041","article-title":"Clinical study on Zhuanggu Zhitong Capsules combined with ibandronate sodium in the treatment of primary osteoporosis","volume":"38","author":"Chen","year":"2023","journal-title":"Drugs Clin."},{"key":"ref_88","first-page":"1715","article-title":"Clinical study on Zhuanggu Zhitong Capsules combined with raloxifene in the treatment of postmenopausal osteoporosis","volume":"36","author":"Yan","year":"2021","journal-title":"Drugs Clin."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Wei, X., Xu, A., Shen, H., and Xie, Y. (2017). Qianggu capsule for the treatment of primary osteoporosis: Evidence from a Chinese patent medicine. BMC Complement. Altern. Med., 17.","DOI":"10.1186\/s12906-017-1617-3"},{"key":"ref_90","first-page":"491","article-title":"Progress of proteomics in osteoporosis","volume":"17","author":"Lin","year":"2024","journal-title":"Chin. J. Osteoporos. Bone Miner. Res."},{"key":"ref_91","first-page":"4","article-title":"Effect of Qianggubao No.1 Formula combined with conventional anti-osteoporosis therapy on periprosthetic bone mineral density of the femur in female patients after total hip arthroplasty","volume":"52","author":"Gao","year":"2021","journal-title":"Fujian J. Tradit. Chin. Med."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"6588","DOI":"10.1021\/acs.jafc.0c01820","article-title":"Evaluating the Activity of Sodium Butyrate to Prevent Osteoporosis in Rats by Promoting Osteal GSK-3\u03b2\/Nrf2 Signaling and Mitochondrial Function","volume":"68","author":"Tang","year":"2020","journal-title":"J. Agric. Food Chem."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1113\/JP280572","article-title":"Regulation of glycolysis by the hypoxia-inducible factor (HIF): Implications for cellular physiology","volume":"599","author":"Kierans","year":"2021","journal-title":"J. Physiol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of cancer: The next generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"2667","DOI":"10.1002\/tox.24140","article-title":"The effect and mechanism of hexokinase-2 on cisplatin resistance in lung cancer cells A549","volume":"39","author":"Xie","year":"2024","journal-title":"Environ. Toxicol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"7323","DOI":"10.1038\/s41467-024-51808-6","article-title":"Structural basis for allosteric regulation of human phosphofructokinase-1","volume":"15","author":"Lynch","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"4222","DOI":"10.1021\/bi048192o","article-title":"Mechanism of the Schiff base forming fructose-1,6-bisphosphate aldolase: Structural analysis of reaction intermediates","volume":"44","author":"Lorentzen","year":"2005","journal-title":"Biochemistry"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"10059","DOI":"10.1080\/07391102.2022.2152870","article-title":"Synergistic effect of conformational changes in phosphoglycerate kinase 1 product release","volume":"41","author":"Liu","year":"2023","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"e0379824","DOI":"10.1128\/mbio.03798-24","article-title":"Pyruvate kinase directly generates GTP in glycolysis, supporting growth and contributing to guanosine toxicity","volume":"16","author":"She","year":"2025","journal-title":"mBio"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"E169","DOI":"10.1152\/ajpendo.00066.2010","article-title":"Measuring GLUT4 translocation in mature muscle fibers","volume":"299","author":"Lauritzen","year":"2010","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1996","DOI":"10.1128\/AEM.03116-14","article-title":"Metabolic engineering of an ATP-neutral Embden-Meyerhof-Parnas pathway in Corynebacterium glutamicum: Growth restoration by an adaptive point mutation in NADH dehydrogenase","volume":"81","author":"Lindner","year":"2015","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Urba\u0144ska, K., and Orzechowski, A. (2019). Unappreciated Role of LDHA and LDHB to Control Apoptosis and Autophagy in Tumor Cells. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20092085"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1038\/s42255-020-0243-4","article-title":"Lactate: The ugly duckling of energy metabolism","volume":"2","author":"Rabinowitz","year":"2020","journal-title":"Nat. Metab."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"2553","DOI":"10.3892\/etm.2016.3179","article-title":"Allicin inhibits oxidative stress-induced mitochondrial dysfunction and apoptosis by promoting PI3K\/AKT and CREB\/ERK signaling in osteoblast cells","volume":"11","author":"Ding","year":"2016","journal-title":"Exp. Ther. Med."},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Liu, J., Gao, Z., and Liu, X. (2024). Mitochondrial dysfunction and therapeutic perspectives in osteoporosis. Front. Endocrinol., 15.","DOI":"10.3389\/fendo.2024.1325317"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"11392","DOI":"10.1074\/jbc.M110927200","article-title":"Increased hexokinase activity, of either ectopic or endogenous origin, protects renal epithelial cells against acute oxidant-induced cell death","volume":"277","author":"Bryson","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Bhardwaj, V., and He, J. (2020). Reactive Oxygen Species, Metabolic Plasticity, and Drug Resistance in Cancer. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21103412"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1795","DOI":"10.1042\/BCJ20190888","article-title":"Glut1 expression is increased by p53 reduction to switch metabolism to glycolysis during osteoblast differentiation","volume":"477","author":"Ohnishi","year":"2020","journal-title":"Biochem. J."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1111\/j.1365-2362.1973.tb00333.x","article-title":"Red cell glycolysis in a case of 3-phosphoglycerate kinase deficiency","volume":"3","author":"Arese","year":"1973","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"35153","DOI":"10.1074\/jbc.M112.400002","article-title":"Inactivation of pyruvate dehydrogenase kinase 2 by mitochondrial reactive oxygen species","volume":"287","author":"Hurd","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Sun, W., Wang, B., Qu, X.L., Zheng, B.Q., Huang, W.D., Sun, Z.W., Wang, C.M., and Chen, Y. (2019). Metabolism of Reactive Oxygen Species in Osteosarcoma and Potential Treatment Applications. Cells, 9.","DOI":"10.3390\/cells9010087"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"e70299","DOI":"10.1111\/jcmm.70299","article-title":"Advances in Osteoblast and Mitochondrial Dynamics and Their Transfer in Osteoporosis","volume":"28","author":"Liu","year":"2024","journal-title":"J. Cell. Mol. Med."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"2432","DOI":"10.1002\/jbmr.4142","article-title":"Lactate Dehydrogenase Inhibition With Oxamate Exerts Bone Anabolic Effect","volume":"35","author":"Hollenberg","year":"2020","journal-title":"J. Bone Min. Res."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.jphs.2023.09.005","article-title":"Lactate dehydrogenase A inhibition prevents RANKL-induced osteoclastogenesis by reducing enhanced glycolysis","volume":"153","author":"Nishioku","year":"2023","journal-title":"J. Pharmacol. Sci."},{"key":"ref_115","first-page":"560","article-title":"Irisin: A novel regulator of bone metabolism","volume":"14","author":"Zong","year":"2021","journal-title":"Chin. J. Osteoporos. Bone Miner. Res."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.bone.2018.05.013","article-title":"The bone anabolic effects of irisin are through preferential stimulation of aerobic glycolysis","volume":"114","author":"Zhang","year":"2018","journal-title":"Bone"},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"Feng, Z., Ou, Y., and Hao, L. (2022). The roles of glycolysis in osteosarcoma. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.950886"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1007\/s13402-024-00943-9","article-title":"The emerging role of CARM1 in cancer","volume":"47","author":"Xie","year":"2024","journal-title":"Cell. Oncol."},{"key":"ref_119","unstructured":"Zhang, L. (2023). Study on the Role and Mechanism of CARM1-Mediated Metabolic Reprogramming of Osteoblasts and Osteoclasts in the Pathogenesis of Osteoporosis. [Ph.D. Thesis, Shandong University]. (In Chinese)."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"117447","DOI":"10.1016\/j.biopha.2024.117447","article-title":"Niacin regulates glucose metabolism and osteogenic differentiation via the SIRT2-C\/EBP\u03b2-AREG signaling axis","volume":"180","author":"Ma","year":"2024","journal-title":"Biomed. Pharmacother."},{"key":"ref_121","unstructured":"Song, J.Y. (2023). Study on the Anti-Osteoporosis Effect of Purified Polysaccharides from Eucommia ulmoides Bark by Promoting Osteogenic Differentiation Through the ERK\/BMP-2\/Smad Pathway. [Ph.D. Thesis, Jilin University]. (In Chinese)."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"106537","DOI":"10.1016\/j.biocel.2024.106537","article-title":"Identification of PKM2 as a pyroptosis-related key gene aggravates senile osteoporosis via the NLRP3\/Caspase-1\/GSDMD signaling pathway","volume":"169","author":"Li","year":"2024","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.1038\/s41418-022-01022-y","article-title":"Targeting mitochondrial metabolism for precision medicine in cancer","volume":"29","year":"2022","journal-title":"Cell Death Differ."},{"key":"ref_124","doi-asserted-by":"crossref","unstructured":"Bellissimo, M.P., Roberts, J.L., Jones, D.P., Liu, K.H., Taibl, K.R., Uppal, K., Weitzmann, M.N., Pacifici, R., Drissi, H., and Ziegler, T.R. (2020). Metabolomic Associations with Serum Bone Turnover Markers. Nutrients, 12.","DOI":"10.3390\/nu12103161"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"15621","DOI":"10.1038\/ncomms15621","article-title":"Succinate and its G-protein-coupled receptor stimulates osteoclastogenesis","volume":"8","author":"Guo","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"115056","DOI":"10.1016\/j.bone.2019.115056","article-title":"IDH2 deficiency increases bone mass with reduced osteoclastogenesis by limiting RANKL expression in osteoblasts","volume":"129","author":"Lee","year":"2019","journal-title":"Bone"},{"key":"ref_127","first-page":"e5126","article-title":"In-Gel Activity Assay of Mammalian Mitochondrial and Cytosolic Aconitases, Surrogate Markers of Compartment-Specific Oxidative Stress and Iron Status","volume":"14","author":"Tong","year":"2024","journal-title":"Bio-Protoc. J."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.freeradbiomed.2021.04.027","article-title":"Hypoxia inhibits RANKL-induced ferritinophagy and protects osteoclasts from ferroptosis","volume":"169","author":"Ni","year":"2021","journal-title":"Free Radic. Biol. Med."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"4748","DOI":"10.1021\/jm020218r","article-title":"The effect of exchanging various substituents at the 2-position of 2-methoxyestradiol on cytotoxicity in human cancer cell cultures and inhibition of tubulin polymerization","volume":"45","author":"Cushman","year":"2002","journal-title":"J. Med. Chem."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"6700","DOI":"10.1021\/jm070639e","article-title":"Synthesis and in vivo antitumor evaluation of 2-methoxyestradiol 3-phosphate, 17-phosphate, and 3,17-diphosphate","volume":"50","author":"Edsall","year":"2007","journal-title":"J. Med. Chem."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"129970","DOI":"10.1016\/j.ijbiomac.2024.129970","article-title":"Targeting the PDK\/PDH axis to reverse metabolic abnormalities by structure-based virtual screening with in vitro and in vivo experiments","volume":"262","author":"Yue","year":"2024","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1007\/s10974-024-09679-3","article-title":"Inhibition of the ubiquitin-proteasome system reduces the abundance of pyruvate dehydrogenase kinase 1 in cultured myotubes","volume":"45","author":"Kociper","year":"2024","journal-title":"J. Muscle Res. Cell Motil."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1038\/s42255-024-01187-5","article-title":"The pentose phosphate pathway controls oxidative protein folding and prevents ferroptosis in chondrocytes","volume":"7","author":"Loopmans","year":"2025","journal-title":"Nat. Metab."},{"key":"ref_134","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 Min. Res."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"e100615","DOI":"10.15252\/embj.2018100615","article-title":"Alpha-ketoglutarate: A \u201cmagic\u201d metabolite in early germ cell development","volume":"38","author":"Lu","year":"2019","journal-title":"EMBO J."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1038\/nature10860","article-title":"IDH mutation impairs histone demethylation and results in a block to cell differentiation","volume":"483","author":"Lu","year":"2012","journal-title":"Nature"},{"key":"ref_137","first-page":"4307","article-title":"Low-dose dexamethasone affects osteoblast viability by inducing autophagy via intracellular ROS","volume":"17","author":"Zhang","year":"2018","journal-title":"Mol. Med. Rep."},{"key":"ref_138","first-page":"11","article-title":"Research progress on the relationship between mitochondria and osteogenic differentiation of bone marrow mesenchymal stem cells","volume":"39","author":"Li","year":"2023","journal-title":"J. Oral Sci. Res."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1038\/s41586-025-08667-y","article-title":"Structure of mitochondrial pyruvate carrier and its inhibition mechanism","volume":"641","author":"He","year":"2025","journal-title":"Nature"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"101688","DOI":"10.1016\/j.bonr.2023.101688","article-title":"Oxidative phosphorylation in bone cells","volume":"18","author":"Sabini","year":"2023","journal-title":"Bone Rep."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1016\/j.cmet.2022.04.010","article-title":"The crosstalk between bone remodeling and energy metabolism: A translational perspective","volume":"34","author":"Karsenty","year":"2022","journal-title":"Cell Metab."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1111\/brv.12140","article-title":"The return of metabolism: Biochemistry and physiology of the pentose phosphate pathway","volume":"90","author":"Stincone","year":"2015","journal-title":"Biol. Rev. Camb. Philos. Soc."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.cbi.2011.02.003","article-title":"The toxic effect of fluoride on MG-63 osteoblast cells is also dependent on the production of nitric oxide","volume":"190","author":"Bergandi","year":"2011","journal-title":"Chem. Biol. Interact."},{"key":"ref_144","doi-asserted-by":"crossref","unstructured":"Chen, P.-H., Tjong, W.-Y., Yang, H.-C., Liu, H.-Y., Stern, A., and Chiu, D.T.-Y. (2022). Glucose-6-Phosphate Dehydrogenase, Redox Homeostasis and Embryogenesis. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23042017"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"101594","DOI":"10.1016\/j.bonr.2022.101594","article-title":"Cell energy metabolism and bone formation","volume":"16","author":"Sautchuk","year":"2022","journal-title":"Bone Rep."},{"key":"ref_146","doi-asserted-by":"crossref","unstructured":"Luo, J., Li, L., Shi, W., Xu, K., Shen, Y., and Dai, B. (2025). Oxidative stress and inflammation: Roles in osteoporosis. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1611932"},{"key":"ref_147","doi-asserted-by":"crossref","unstructured":"Wang, J.X., Choi, S.Y.C., Niu, X., Kang, N., Xue, H., Killam, J., and Wang, Y. (2020). Lactic Acid and an Acidic Tumor Microenvironment suppress Anticancer Immunity. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21218363"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1083\/jcb.200401138","article-title":"Runx2 induces osteoblast and chondrocyte differentiation and enhances their migration by coupling with PI3K-Akt signaling","volume":"166","author":"Fujita","year":"2004","journal-title":"J. Cell Biol."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"2817","DOI":"10.1002\/1873-3468.13608","article-title":"The paradox of metabolism in quiescent stem cells","volume":"593","author":"Coller","year":"2019","journal-title":"FEBS Lett."},{"key":"ref_150","doi-asserted-by":"crossref","unstructured":"Bousch, J.F., Beyersdorf, C., Schultz, K., Windolf, J., Suschek, C.V., and Maus, U. (2024). Proinflammatory Cytokines Enhance the Mineralization, Proliferation, and Metabolic Activity of Primary Human Osteoblast-like Cells. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms252212358"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1186\/s12951-025-03235-y","article-title":"Acid-responsive aggregated carrot-derived nanoantioxidants alleviate oxidative stress and restore osteoblast activity","volume":"23","author":"Peng","year":"2025","journal-title":"J. Nanobiotechnol."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1136\/ard-2023-224774","article-title":"Acod1-mediated inhibition of aerobic glycolysis suppresses osteoclast differentiation and attenuates bone erosion in arthritis","volume":"83","author":"Kachler","year":"2024","journal-title":"Ann. Rheum. Dis."},{"key":"ref_153","first-page":"492","article-title":"The PCK2-glycolysis axis assists three-dimensional-stiffness maintaining stem cell osteogenesis","volume":"18","author":"Li","year":"2022","journal-title":"Bioact. Mater."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"e13058","DOI":"10.1111\/cpr.13058","article-title":"Cathepsin K deficiency promotes alveolar bone regeneration by promoting jaw bone marrow mesenchymal stem cells proliferation and differentiation via glycolysis pathway","volume":"54","author":"Zhang","year":"2021","journal-title":"Cell Prolif."},{"key":"ref_155","doi-asserted-by":"crossref","unstructured":"Lian, W.S., Wu, R.W., Lin, Y.H., Chen, Y.S., Jahr, H., and Wang, F.S. (2024). Tricarboxylic Acid Cycle Regulation of Metabolic Program, Redox System, and Epigenetic Remodeling for Bone Health and Disease. Antioxidants, 13.","DOI":"10.3390\/antiox13040470"},{"key":"ref_156","doi-asserted-by":"crossref","unstructured":"Buchanan, J.L., Rauckhorst, A.J., and Taylor, E.B. (2023). 3-hydroxykynurenine is a ROS-inducing cytotoxic tryptophan metabolite that disrupts the TCA cycle. bioRxiv.","DOI":"10.1101\/2023.07.10.548411"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"2449","DOI":"10.1021\/pr801046m","article-title":"Oxidative damage of mitochondrial proteins contributes to fruit senescence: A redox proteomics analysis","volume":"8","author":"Qin","year":"2009","journal-title":"J. Proteome Res."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"41364","DOI":"10.1039\/D5RA06586K","article-title":"Nanoparticles in the treatment of osteoporosis: Recent advances in nanoparticles for the treatment of osteoporosis","volume":"15","author":"Li","year":"2025","journal-title":"RSC Adv."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"110488","DOI":"10.1016\/j.cellsig.2022.110488","article-title":"The Warburg effect in osteoporosis: Cellular signaling and epigenetic regulation of energy metabolic events to targeting the osteocalcin for phenotypic alteration","volume":"100","author":"Vadivalagan","year":"2022","journal-title":"Cell. Signal."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"e16919","DOI":"10.1016\/j.heliyon.2023.e16919","article-title":"Natural products targeting inflammation-related metabolic disorders: A comprehensive review","volume":"9","author":"Nainu","year":"2023","journal-title":"Heliyon"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1007\/s00018-025-05845-z","article-title":"Quercetin alleviates acute pancreatitis by modulating glycolysis and mitochondrial function via PFKFB3 inhibition","volume":"82","author":"Jiang","year":"2025","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1002\/jbmr.4240","article-title":"Metabolomics Insights into Osteoporosis Through Association with Bone Mineral Density","volume":"36","author":"Zhang","year":"2021","journal-title":"J. Bone Min. Res."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1111\/sltb.12957","article-title":"Suicidal behaviors in patients with chronic physical illness: A test on the interpersonal theory of suicide","volume":"53","author":"Shim","year":"2023","journal-title":"Suicide Life Threat. Behav."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"116880","DOI":"10.1016\/j.bone.2023.116880","article-title":"Advanced glycation and glycoxidation end products in bone","volume":"176","author":"Wang","year":"2023","journal-title":"Bone"},{"key":"ref_165","doi-asserted-by":"crossref","unstructured":"Guo, J., Huang, Q., Zhou, Y., Xu, Y., Zong, C., Shen, P., Ma, Y., Zhang, J., Cui, Y., and Yu, L. (2022). Typing characteristics of metabolism-related genes in osteoporosis. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.999157"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/10\/4536\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T04:46:42Z","timestamp":1779770802000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/10\/4536"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,18]]},"references-count":165,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["ijms27104536"],"URL":"https:\/\/doi.org\/10.3390\/ijms27104536","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,18]]}}}