{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T21:25:11Z","timestamp":1790630711053,"version":"4.1.0"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,4,19]],"date-time":"2022-04-19T00:00:00Z","timestamp":1650326400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p>As an important public health problem, osteoporosis (OP) in China is also in an upward trend year by year. As a standard method for diagnosing OP, dual-energy X-ray absorptiometry (DXA) cannot analyze the pathological process but only see the results. It is difficult to evaluate the early diagnosis of OP. Our study was carried out through a serum metabolomic study of OP in Chinese postmenopausal women on untargeted gas chromatography (GC)\/liquid chromatography (LC)\u2013mass spectrometry (MS) to find possible diagnostic markers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>50 Chinese postmenopausal women with osteoporosis and 50 age-matched women were selected as normal controls. We first used untargeted GC\/LC-MS to analyze the serum of these participants and then combined it with a large number of multivariate statistical analyses to analyze the data. Finally, based on a multidimensional analysis of the metabolites, the most critical metabolites were considered to be biomarkers of OP in postmenopausal women. Further, biomarkers identified relevant metabolic pathways, followed by a map of metabolic pathways found in the database.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found that there may be metabolic pathway disorders like glucose metabolism, lipid metabolism, and amino acid metabolism in postmenopausal women with OP. 18 differential metabolites are considered to be potential biomarkers of OP in postmenopausal women which are a major factor in metabolism and bone physiological function.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These findings can be applied to clinical work through further validation studies. It also shows that metabonomic analysis has great potential in the application of early diagnosis and recurrence monitoring in postmenopausal OP women.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2022.849076","type":"journal-article","created":{"date-parts":[[2022,4,19]],"date-time":"2022-04-19T05:43:36Z","timestamp":1650347016000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":23,"title":["Discovery of Potential Biomarkers for Postmenopausal Osteoporosis Based on Untargeted GC\/LC-MS"],"prefix":"10.3389","volume":"13","author":[{"given":"Jun","family":"Kou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunyang","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengping","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Da","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Gu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,4,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.5534\/WJMH.200099","article-title":"Gender Differences in Osteoporosis: A Single-Center Observational Study","volume":"39","author":"De Martinis","year":"2021","journal-title":"World J Men\u2019s Health"},{"key":"B2","doi-asserted-by":"publisher","first-page":"494","DOI":"10.1097\/AOG.0000000000004514","article-title":"American College of Obstetricians and Gynecologists\u2019 Committee on Clinical Practice Guidelines\u2013Gynecology. Osteoporosis Prevention, Screening, and Diagnosis: ACOG Clinical Practice Guideline No. 1","volume":"138","year":"2021","journal-title":"Obstetr Gynecol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2005.08.047","article-title":"Epidemiology, Etiology, and Diagnosis of Osteoporosis","volume":"194","author":"Lane","year":"2005","journal-title":"Am J Obstetr Gynecol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1007\/s11999-011-1780-7","article-title":"Gender Differences in Osteoporosis and Fractures","volume":"469","author":"Cawthon","year":"2011","journal-title":"Clin Orthopaedics Related Res"},{"key":"B5","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1038\/s41574-019-0282-7","article-title":"A Road Map for Understanding Molecular and Genetic Determinants of Osteoporosis","volume":"16","author":"Yang","year":"2020","journal-title":"Nat Rev Endocrinol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.4342","article-title":"Bone Radiomics Score Derived From DXA Hip Images Enhances Hip Fracture Prediction in Older Women","volume":"36","author":"Hong","year":"2021","journal-title":"J Bone Mineral Res: Off J Am Soc Bone Mineral Res"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2014.12.017","article-title":"Metabolomics for Laboratory Diagnostics","volume":"113","author":"Bujak","year":"2015","journal-title":"J Pharm Biomed Anal"},{"key":"B8","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.cbpa.2015.10.012","article-title":"High-Throughput Platforms for Metabolomics","volume":"30","author":"de Raad","year":"2016","journal-title":"Curr Opin Chem Biol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.03.055","article-title":"Metabolomics and Isotope Tracing","volume":"173","author":"Jang","year":"2018","journal-title":"Cell"},{"key":"B10","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/j.aca.2015.10.001","article-title":"From Sample Treatment to Biomarker Discovery: A Tutorial for Untargeted Metabolomics Based on GC-(EI)-Q-MS","volume":"900","author":"Mastrangelo","year":"2015","journal-title":"Analytica Chim Acta"},{"key":"B11","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1016\/j.chroma.2016.10.064","article-title":"Improved Conventional and Microwave-Assisted Silylation Protocols for Simultaneous Gas Chromatographic Determination of Tocopherols and Sterols: Method Development and Multi-Response Optimization","volume":"1476","author":"Poojary","year":"2016","journal-title":"J Chromatography A"},{"key":"B12","doi-asserted-by":"publisher","first-page":"20150366","DOI":"10.1098\/rsta.2015.0366","article-title":"Quantitative Mass Spectrometry Methods for Pharmaceutical Analysis","volume":"374","author":"Loos","year":"2016","journal-title":"Philos Trans Ser A Mathematical Physical Eng Sci"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.25.547","article-title":"Current Developments in LC-MS for Pharmaceutical Analysis","volume":"25","author":"Lim","year":"2002","journal-title":"Biol Pharm Bull"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.2018","article-title":"Association Between the Metabolome and Low Bone Mineral Density in Taiwanese Women Determined by (1)H NMR Spectroscopy","volume":"29","author":"You","year":"2014","journal-title":"J Bone Mineral Res: Off J Am Soc Bone Mineral Res"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph15051045","article-title":"Association of Plasma Lipids and Polar Metabolites With Low Bone Mineral Density in Singaporean-Chinese Menopausal Women: A Pilot Study","volume":"15","author":"Cabrera","year":"2018","journal-title":"Int J Environ Res Public Health"},{"key":"B16","doi-asserted-by":"publisher","first-page":"e0217348","DOI":"10.1371\/journal.pone.0217348","article-title":"Osteopenia-Osteoporosis Discrimination in Postmenopausal Women by 1H NMR-Based Metabonomics","volume":"14","author":"Pontes","year":"2019","journal-title":"PloS One"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1039\/c6mb00181e","article-title":"Association Between the Metabolome and Bone Mineral Density in Pre- and Post-Menopausal Chinese Women Using GC-MS","volume":"12","author":"Qi","year":"2016","journal-title":"Mol Biosyst"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.bonr.2018.06.004","article-title":"Metabolomics-Based Profiles Predictive of Low Bone Mass in Menopausal Women","volume":"9","author":"Miyamoto","year":"2018","journal-title":"Bone Rep"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1007\/s00198-019-04892-0","article-title":"Discovery of Potential Biomarkers for Osteoporosis Using LC-MS\/MS Metabolomic Methods. Osteoporosis International: A Journal Established as Result of Cooperation Between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA","volume":"30","author":"Wang","year":"2019","journal-title":"Osteoporos Int"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1097\/MCO.0000000000000200","article-title":"Serum Metabolomics in Animal Models and Human Disease","volume":"18","author":"James","year":"2015","journal-title":"Curr Opin Clin Nutr Metab Care"},{"key":"B21","doi-asserted-by":"publisher","first-page":"572","DOI":"10.1038\/s41592-018-0093-0","article-title":"Contrasting PCA Across Datasets","volume":"15","author":"Nawy","year":"2018","journal-title":"Nat Methods"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.talanta.2005.03.006","article-title":"Direct and Two-Stage Data Analysis Procedures Based on PCA, PLS-DA and ANN for ISE-Based Electronic Tongue-Effect of Supervised Feature Extraction","volume":"67","author":"Ciosek","year":"2005","journal-title":"Talanta"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinbiochem.2012.05.012","article-title":"Distinguishing Pancreatic Cancer From Chronic Pancreatitis and Healthy Individuals by (1)H Nuclear Magnetic Resonance-Based Metabonomic Profiles","volume":"45","author":"Zhang","year":"2012","journal-title":"Clin Biochem"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1039\/b807369d","article-title":"Integrated GC-MS and LC-MS Plasma Metabonomics Analysis of Ankylosing Spondylitis","volume":"133","author":"Gao","year":"2008","journal-title":"Analyst"},{"key":"B25","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1186\/s13075-016-1139-2","article-title":"Plasma, Urine and Ligament Tissue Metabolite Profiling Reveals Potential Biomarkers of Ankylosing Spondylitis Using NMR-Based Metabolic Profiles","volume":"18","author":"Wang","year":"2016","journal-title":"Arthritis Res Ther"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M110.004945","article-title":"Serum and Urine Metabolite Profiling Reveals Potential Biomarkers of Human Hepatocellular Carcinoma","volume":"10","author":"Chen","year":"2011","journal-title":"Mol Cell Proteomics: MCP"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.4101","article-title":"Metabolomics Activity Screening for Identifying Metabolites That Modulate Phenotype","volume":"36","author":"Guijas","year":"2018","journal-title":"Nat Biotechnol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1038\/nrm.2016.25","article-title":"Metabolomics: Beyond Biomarkers and Towards Mechanisms","volume":"17","author":"Johnson","year":"2016","journal-title":"Nat Rev Mol Cell Biol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.3390\/ijms17122018","article-title":"Metabolomics and Its Application in the Development of Discovering Biomarkers for Osteoporosis Research","volume":"17","author":"Lv","year":"2016","journal-title":"Int J Mol Sci"},{"key":"B30","doi-asserted-by":"publisher","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":"B31","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1210\/er.2009-0024","article-title":"From Estrogen-Centric to Aging and Oxidative Stress: A Revised Perspective of the Pathogenesis of Osteoporosis","volume":"31","author":"Manolagas","year":"2010","journal-title":"Endocrine Rev"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1172\/JCI17215","article-title":"Role of RANK Ligand in Mediating Increased Bone Resorption in Early Postmenopausal Women","volume":"111","author":"Eghbali-Fatourechi","year":"2003","journal-title":"J Clin Invest"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1210\/er.2017-00064","article-title":"Energy Metabolism of the Osteoblast: Implications for Osteoporosis","volume":"38","author":"Lee","year":"2017","journal-title":"Endocrine Rev"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.niox.2014.12.007","article-title":"Hydrogen Sulfide Improves Glucose Metabolism and Prevents Hypertrophy in Cardiomyocytes","volume":"46","author":"Liang","year":"2015","journal-title":"Nitric Oxide: Biol Chem"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/0024-3205(89)90120-3","article-title":"Lactobionic Acid as an Iron Chelator: A Rationale for its Effectiveness as an Organ Preservant","volume":"45","author":"Isaacson","year":"1989","journal-title":"Life Sci"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.3390\/nu9050506","article-title":"Fat, Sugar, and Bone Health: A Complex Relationship","volume":"9","author":"Tian","year":"2017","journal-title":"Nutrients"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.25191","article-title":"Lipidomics of Mesenchymal Stromal Cells: Understanding the Adaptation of Phospholipid Profile in Response to Pro-Inflammatory Cytokines","volume":"231","author":"Campos","year":"2016","journal-title":"J Cell Physiol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1038\/srep46715","article-title":"Phosphatidylethanolamine Dynamics are Required for Osteoclast Fusion","volume":"7","author":"Irie","year":"2017","journal-title":"Sci Rep"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2003.10.032","article-title":"Inhibition of Osteoclast Differentiation and Bone Resorption by a Novel Lysophosphatidylcholine Derivative, SCOH","volume":"67","author":"Kwak","year":"2004","journal-title":"Biochem Pharmacol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.1751","article-title":"Inactivation of Anoctamin-6\/Tmem16f, A Regulator of Phosphatidylserine Scrambling in Osteoblasts, Leads to Decreased Mineral Deposition in Skeletal Tissues","volume":"28","author":"Ehlen","year":"2013","journal-title":"J Bone Mineral Res: Off J Am Soc Bone Mineral Res"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M030650","article-title":"Aging Bone Marrow Mesenchymal Stromal Cells Have Altered Membrane Glycerophospholipid Composition and Functionality","volume":"54","author":"Kilpinen","year":"2013","journal-title":"J Lipid Res"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0714.1989.tb01564.x","article-title":"Regulation of Bone Cell Metabolism","volume":"18","author":"Hagel-Bradway","year":"1989","journal-title":"J Oral Pathol Med: Off Publ Int Assoc Oral Pathol Am Acad Oral Pathol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1997.6795","article-title":"Regulation of Osteoclastic Bone Resorption by Glucose","volume":"235","author":"Williams","year":"1997","journal-title":"Biochem Biophys Res Commun"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.5650040604","article-title":"The Effect of Tartrate on Bone Cell Acid Phosphatase Activity: A Quantitative Cytochemical Study","volume":"4","author":"Webber","year":"1989","journal-title":"J Bone Mineral Res: Off J Am Soc Bone Mineral Res"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0712331105","article-title":"Structure of Glycerol-3-Phosphate Dehydrogenase, an Essential Monotopic Membrane Enzyme Involved in Respiration and Metabolism","volume":"105","author":"Yeh","year":"2008","journal-title":"Proc Natl Acad Sci U States America"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1517\/14728222.8.6.643","article-title":"Clues for New Therapeutics in Osteoporosis and Periodontal Disease: New Roles for Lipoxygenases","volume":"8","author":"Serhan","year":"2004","journal-title":"Expert Opin Ther Targets"},{"key":"B47","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/j.biochi.2020.08.004","article-title":"Osteoporosis: A Role for Lipids","volume":"178","author":"During","year":"2020","journal-title":"Biochimie"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1042\/BST0320785","article-title":"The Role of SHIP1 in Macrophage Programming and Activation","volume":"32","author":"Rauh","year":"2004","journal-title":"Biochem Soc Trans"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(17)30184-5","article-title":"Use of Bone Turnover Markers in Postmenopausal Osteoporosis","volume":"5","author":"Eastell","year":"2017","journal-title":"Lancet Diabetes Endocrinol"},{"key":"B50","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.bone.2016.10.027","article-title":"A Serum Metabolomics-Based Profile in Low Bone Mineral Density Postmenopausal Women","volume":"95","author":"Miyamoto","year":"2017","journal-title":"Bone"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2022.849076\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,19]],"date-time":"2022-04-19T05:43:38Z","timestamp":1650347018000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2022.849076\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,19]]},"references-count":50,"alternative-id":["10.3389\/fendo.2022.849076"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2022.849076","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,19]]},"article-number":"849076"}}