{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T23:47:17Z","timestamp":1792712837171,"version":"4.5.0"},"reference-count":101,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2016,12,2]],"date-time":"2016-12-02T00:00:00Z","timestamp":1480636800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Osteoporosis is a progressive skeletal disorder characterized by low bone mass and increased risk of fracture in later life. The incidence and costs associated with treating osteoporosis cause heavy socio-economic burden. Currently, the diagnosis of osteoporosis mainly depends on bone mineral density and bone turnover markers. However, these indexes are not sensitive and accurate enough to reflect the osteoporosis progression. Metabolomics offers the potential for a holistic approach for clinical diagnoses and treatment, as well as understanding of the pathological mechanism of osteoporosis. In this review, we firstly describe the study subjects of osteoporosis and bio-sample preparation procedures for different analytic purposes, followed by illustrating the biomarkers with potentially predictive, diagnosis and pharmaceutical values when applied in osteoporosis research. Then, we summarize the published metabolic pathways related to osteoporosis. Furthermore, we discuss the importance of chronological data and combination of multi-omics in fully understanding osteoporosis. The application of metabolomics in osteoporosis could provide researchers the opportunity to gain new insight into the metabolic profiling and pathophysiological mechanisms. However, there is still much to be done to validate the potential biomarkers responsible for the progression of osteoporosis and there are still many details needed to be further elucidated.<\/jats:p>","DOI":"10.3390\/ijms17122018","type":"journal-article","created":{"date-parts":[[2016,12,2]],"date-time":"2016-12-02T10:36:37Z","timestamp":1480674997000},"page":"2018","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":56,"title":["Metabolomics and Its Application in the Development of Discovering Biomarkers for Osteoporosis Research"],"prefix":"10.3390","volume":"17","author":[{"given":"Huanhuan","family":"Lv","sequence":"first","affiliation":[{"name":"Institute for Advancing Translational Medicine in Bone &amp; Joint Disease, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong 999077, China"},{"name":"Institute of Precision Medicine and Innovative Drug Discovery, HKBU (Haimen) Institute of Science and Technology, Haimen 226133, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Jiang","sequence":"additional","affiliation":[{"name":"Institute for Advancing Translational Medicine in Bone &amp; Joint Disease, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong 999077, China"},{"name":"Institute of Precision Medicine and Innovative Drug Discovery, HKBU (Haimen) Institute of Science and Technology, Haimen 226133, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daogang","family":"Guan","sequence":"additional","affiliation":[{"name":"Institute for Advancing Translational Medicine in Bone &amp; Joint Disease, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong 999077, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Lu","sequence":"additional","affiliation":[{"name":"Institute for Advancing Translational Medicine in Bone &amp; Joint Disease, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong 999077, China"},{"name":"Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baosheng","family":"Guo","sequence":"additional","affiliation":[{"name":"Institute for Advancing Translational Medicine in Bone &amp; Joint Disease, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong 999077, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chileung","family":"Chan","sequence":"additional","affiliation":[{"name":"Institute for Advancing Translational Medicine in Bone &amp; Joint Disease, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong 999077, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Songlin","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Spine Surgery, Shenzheng People\u2019s Hospital, Shenzheng 518020, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baoqin","family":"Liu","sequence":"additional","affiliation":[{"name":"Zhengzhou Hospital of Traditional Chinese Medicine, Zhengzhou 450007, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenwei","family":"Guo","sequence":"additional","affiliation":[{"name":"Zhengzhou Hospital of Traditional Chinese Medicine, Zhengzhou 450007, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hailong","family":"Zhu","sequence":"additional","affiliation":[{"name":"Institute for Advancing Translational Medicine in Bone &amp; Joint Disease, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong 999077, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuegong","family":"Xu","sequence":"additional","affiliation":[{"name":"Zhengzhou Hospital of Traditional Chinese Medicine, Zhengzhou 450007, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aiping","family":"Lu","sequence":"additional","affiliation":[{"name":"Institute for Advancing Translational Medicine in Bone &amp; Joint Disease, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong 999077, China"},{"name":"Institute of Arthritis Research, Shanghai Academy of Chinese Medical Sciences, Guanghua Integrative Medicine Hospital\/Shanghai University of Traditional Chinese Medicine, Shanghai 200052, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7807-7695","authenticated-orcid":false,"given":"Ge","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute for Advancing Translational Medicine in Bone &amp; Joint Disease, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong 999077, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2016,12,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.jchromb.2004.07.045","article-title":"HPLC-MS-based methods for the study of metabonomics","volume":"817","author":"Wilson","year":"2005","journal-title":"J. Chromatogr. B"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/s11306-009-0191-1","article-title":"Dynamic metabolomic data analysis: A tutorial review","volume":"6","author":"Smilde","year":"2010","journal-title":"Metabolomics"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.3390\/ijms17071148","article-title":"Potential metabolic biomarkers to identify interstitial lung abnormalities","volume":"17","author":"Tan","year":"2016","journal-title":"Int. J. Mol. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1016\/j.neurobiolaging.2010.09.013","article-title":"Serum fatty acid profiles using GC-MS and multivariate statistical analysis: Potential biomarkers of Alzheimer\u2019s disease","volume":"33","author":"Wang","year":"2012","journal-title":"Neurobiol. Aging"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1007\/s11306-010-0270-3","article-title":"Bioinformatics tools for cancer metabolomics","volume":"7","author":"Blekherman","year":"2011","journal-title":"Metabolomics"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1007\/s11306-016-0965-1","article-title":"Metabolomic study of the bone trabecula of osteonecrosis femoral head patients based on UPLC\u2013MS\/MS","volume":"12","author":"Zhu","year":"2016","journal-title":"Metabolomics"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/j.yexcr.2014.04.019","article-title":"Disordered glycometabolism involved in pathogenesis of Kashin-Beck disease, an endemic osteoarthritis in China","volume":"326","author":"Wu","year":"2014","journal-title":"Exp. Cell Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1007\/s11306-009-0184-0","article-title":"Urinary metabolomics as a potentially novel diagnostic and stratification tool for knee osteoarthritis","volume":"6","author":"Li","year":"2009","journal-title":"Metabolomics"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1136\/ard.2009.120857","article-title":"Serum branched-chain amino acid to histidine ratio: A novel metabolomic biomarker of knee osteoarthritis","volume":"69","author":"Zhai","year":"2010","journal-title":"Ann. Rheum. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1097\/gme.0b013e31815c1e7f","article-title":"Soy isoflavones in the management of postmenopausal osteoporosis","volume":"15","author":"Atmaca","year":"2008","journal-title":"Menopause"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.1002\/jbmr.2286","article-title":"Osteoporosis: A lifecourse approach","volume":"29","author":"Harvey","year":"2014","journal-title":"J. Bone Miner. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"154","DOI":"10.4103\/0976-9668.92322","article-title":"Preventive effects of phytoestrogens against postmenopausal osteoporosis as compared to the available therapeutic choices: An overview","volume":"2","author":"Qureshi","year":"2011","journal-title":"J. Nat. Sci. Biol. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1038\/nrrheum.2009.260","article-title":"Osteoporosis: Impact on health and economics","volume":"6","author":"Harvey","year":"2010","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1136\/bmj.303.6808.961","article-title":"Role of peak bone mass and bone loss in postmenopausal osteoporosis: 12 year study","volume":"303","author":"Hansen","year":"1991","journal-title":"Br. Med. J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1007\/BF03345204","article-title":"Biochemical markers of bone metabolism in the assessment of osteoporosis: Useful or not?","volume":"26","author":"Seibel","year":"2003","journal-title":"J. Endocrinol. Investig."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1177\/0004563213515190","article-title":"Biochemical markers of bone turnover-uses and limitations","volume":"51","author":"Hlaing","year":"2014","journal-title":"Ann. Clin. Biochem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1007\/s00774-006-0703-2","article-title":"Age-related changes in bone biochemical markers and their relationship with bone mineral density in normal Chinese women","volume":"24","author":"Pi","year":"2006","journal-title":"J. Bone Miner. Metab."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.1359\/jbmr.2003.18.10.1789","article-title":"Long-Term variability of markers of bone turnover in postmenopausal women and implications for their clinical use: The OFELY study","volume":"18","author":"Patrick","year":"2003","journal-title":"J. Bone Miner. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2622","DOI":"10.1210\/jc.2007-1508","article-title":"Serial assessment of serum bone metabolism markers identifies women with the highest rate of bone loss and osteoporosis risk","volume":"93","author":"Ivaska","year":"2008","journal-title":"J. Clin. Endocr. Metab."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1007\/s00228-006-0174-3","article-title":"An update on biomarkers of bone turnover and their utility in biomedical research and clinical practice","volume":"62","author":"Leeming","year":"2006","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"S2","DOI":"10.1007\/s001980070002","article-title":"The use of biochemical markers of bone turnover in osteoporosis","volume":"11","author":"Delmas","year":"2000","journal-title":"Osteoporos. Int."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2265","DOI":"10.1039\/C6MB00181E","article-title":"Association between the metabolome and bone mineral density in pre- and post-menopausal Chinese women using GC\u2013MS","volume":"12","author":"Qi","year":"2016","journal-title":"Mol. BioSyst."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1002\/bmc.3194","article-title":"Kidney tissue targeted metabolic profiling of glucocorticoid-induced osteoporosis and the proposed therapeutic effects of Rhizoma Drynariae studied using UHPLC\/MS\/MS","volume":"28","author":"Huang","year":"2014","journal-title":"Biomed. Chromatogr."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1517\/17460441.2015.1080685","article-title":"Appropriate models for novel osteoporosis drug discovery and future perspectives","volume":"10","author":"Gennari","year":"2015","journal-title":"Expert Opin. Drug Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.archoralbio.2014.11.005","article-title":"Neuropeptide FF attenuates RANKL-induced differentiation of macrophage-like cells into osteoclast-like cells","volume":"60","author":"Sun","year":"2015","journal-title":"Arch. Oral Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1039\/C4MB00528G","article-title":"A metabolomics study of the inhibitory effect of 17-\u03b2-estradiol on osteoclast proliferation and differentiation","volume":"11","author":"Liu","year":"2015","journal-title":"Mol. BioSyst."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/0169-6009(91)90124-I","article-title":"The ovariectomized rat model of postmenopausal bone loss","volume":"15","author":"Kalu","year":"1991","journal-title":"Bone Miner."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1007\/s00198-007-0394-0","article-title":"Glucocorticoid-induced osteoporosis: Pathophysiology and therapy","volume":"18","author":"Canalis","year":"2007","journal-title":"Osteoporos. Int."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1373\/clinchem.2011.169573","article-title":"Metabolomics and cardiovascular biomarker discovery","volume":"58","author":"Rhee","year":"2012","journal-title":"Clin. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1002\/jbmr.2018","article-title":"Association between the metabolome and low bone mineral density in Taiwanese women determined by 1H NMR spectroscopy","volume":"29","author":"You","year":"2014","journal-title":"J. Bone Miner. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1038\/nprot.2007.95","article-title":"Untargeted large-scale plant metabolomics using liquid chromatography coupled to mass spectrometry","volume":"2","author":"Moco","year":"2007","journal-title":"Nat. Protoc."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1007\/s00216-012-6039-y","article-title":"Current trends and challenges in sample preparation for global metabolomics using liquid chromatography-mass spectrometry","volume":"403","author":"Vuckovic","year":"2012","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.clinbiochem.2010.08.016","article-title":"Applications of liquid chromatography coupled to mass spectrometry-based metabolomics in clinical chemistry and toxicology: A review","volume":"44","author":"Roux","year":"2011","journal-title":"Clin. Biochem."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Ma, B., Liu, J., Zhang, Q., Ying, H., A, J., Sun, J., Wu, D., Wang, Y., Li, J., and Liu, Y. (2013). Metabolomic profiles delineate signature metabolic shifts during estrogen deficiency-induced bone loss in rat by GC-TOF\/MS. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0054965"},{"key":"ref_35","first-page":"843","article-title":"1H NMR-based metabonomics analysis of plasma from osteoporotic rats induced by ovariectomy","volume":"40","author":"Long","year":"2009","journal-title":"Med. Sci. Ed."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.mce.2014.02.007","article-title":"1H NMR metabolic profiling analysis offers evaluation of Nilestriol treatment in ovariectomised rats","volume":"387","author":"Liu","year":"2014","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Chen, S.Y., Yu, H.T., Kao, J.P., Yang, C.C., Chiang, S.S., Mishchuk, D.O., Mau, J.L., and Slupsky, C.M. (2014). An NMR metabolomic study on the effect of alendronate in ovariectomized mice. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0106559"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1016\/j.jff.2015.06.023","article-title":"1H NMR and HPLC\u2013MS\/MS-based global\/targeted metabolomic evaluation of Hypericum perforatum L. intervention for menopause","volume":"17","author":"Liu","year":"2015","journal-title":"J. Funct. Foods"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"149","DOI":"10.3390\/molecules21020149","article-title":"Metabolite profiling reveals the effect of dietary Rubus coreanus vinegar on ovariectomy-induced osteoporosis in a rat model","volume":"21","author":"Lee","year":"2016","journal-title":"Molecules"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.jep.2011.11.017","article-title":"Metabonomic study on the anti-osteoporosis effect of Rhizoma Drynariae and its action mechanism using ultra-performance liquid chromatography-tandem mass spectrometry","volume":"139","author":"Liu","year":"2012","journal-title":"J. Ethnopharmacol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.jchromb.2016.05.019","article-title":"An intergated serum and urinary metabonomic research based on UPLC-MS and therapeutic effects of Gushudan on prednisolone-induced osteoporosis rats","volume":"1027","author":"Huang","year":"2016","journal-title":"J. Chromatogr. B"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1038\/nbt1235","article-title":"Protein biomarker discovery and validation: The long and uncertain path to clinical utility","volume":"24","author":"Rifai","year":"2006","journal-title":"Nat. Biotechnol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1038\/nrd.2016.32","article-title":"Emerging applications of metabolomics in drug discovery and precision medicine","volume":"15","author":"Wishart","year":"2016","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1373\/clinchem.2012.184598","article-title":"New opportunities from the cancer metabolome","volume":"59","author":"Aboud","year":"2013","journal-title":"Clin. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1016\/j.ejphar.2013.06.030","article-title":"Metabonomic profiling in studying anti-osteoporosis effects of strontium fructose 1,6-diphosphate on estrogen deficiency-induced osteoporosis in rats by GC\/TOF-MS","volume":"718","author":"Ma","year":"2013","journal-title":"Eur. J. Pharmacol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.ejphar.2014.01.048","article-title":"Metabolomic evaluation of the response to endocrine therapy in patients with prostate cancer","volume":"729","author":"Huang","year":"2014","journal-title":"Eur. J. Pharmacol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"398S","DOI":"10.1080\/07315724.2001.10719175","article-title":"The role of phytoestrogens in the prevention and treatment of osteoporosis in ovarian hormone deficiency","volume":"20","author":"Arjmandi","year":"2001","journal-title":"J. Am. Coll. Nutr."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"760","DOI":"10.3109\/09513590.2010.487615","article-title":"Metabolomics in serum of ovariectomised rats and those exposed to 17 \u03b2-oestradiol and genistein","volume":"26","author":"Zhu","year":"2010","journal-title":"Gynecol. Endocrinol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2582","DOI":"10.1002\/jbmr.147","article-title":"Development of a novel transdermal patch of alendronate, a nitrogen-containing bisphosphonate, for the treatment of osteoporosis","volume":"25","author":"Kusamori","year":"2010","journal-title":"J. Bone Miner. Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1038\/aps.2011.177","article-title":"Strontium fructose 1,6-diphosphate prevents bone loss in a rat model of postmenopausal osteoporosis via the OPG\/RANKL\/RANK pathway","volume":"33","author":"Ma","year":"2012","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"7635","DOI":"10.3390\/ijms12117635","article-title":"A 1HNMR-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_52","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1038\/aps.2010.196","article-title":"GC-TOF\/MS-based metabolomic profiling of estrogen deficiency-induced obesisty in ovariectomized rats","volume":"32","author":"Ma","year":"2011","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1016\/j.jep.2016.07.037","article-title":"Comparative proteomic and metabolomic analysis reveal the antiosteoporotic molecular mechanism of icariin from Epimedium brevicornu Maxim","volume":"192","author":"Xue","year":"2016","journal-title":"J. Ethnopharmacol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1080\/10826076.2014.883540","article-title":"Metabonomics study of the anti-osteoporosis effect of velvet collagen hydrolysate using rapid resolution liquid chromatography combined with quadrupole time-of-flight tandem mass spectrometry","volume":"38","author":"Li","year":"2014","journal-title":"J. Liq. Chromatogr. Relat. Technol."},{"key":"ref_55","first-page":"658","article-title":"Metabonomic study on protective effect of ethanol extracts of Drynariae rhizoma on osteoporosis in rats urine by using UPLC\u2013MS\/MS","volume":"37","author":"Zhang","year":"2012","journal-title":"China J. Chin. Mater. Medica"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1002\/ptr.5240","article-title":"The application of metabolomics in traditional Chinese medicine opens up a dialogue between Chinese and Western medicine","volume":"29","author":"Cao","year":"2015","journal-title":"Phytother. Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1002\/ptr.1624","article-title":"Metabolomics in the context of systems biology: Bridging traditional Chinese medicine and molecular pharmacology","volume":"19","author":"Wang","year":"2005","journal-title":"Phytother. Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2026","DOI":"10.1055\/s-0030-1250542","article-title":"Metabolomics: Towards understanding traditional Chinese medicine","volume":"76","author":"Zhang","year":"2010","journal-title":"Planta Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1142\/S0192415X1450027X","article-title":"Er-xian Decoction exerts estrogen-like osteoprotective effects in vivo and in vitro","volume":"42","author":"Wong","year":"2014","journal-title":"Am. J. Chin. Med."},{"key":"ref_60","first-page":"241416","article-title":"Comparative effects of er-xian decoction, epimedium herbs, and icariin with estrogen on bone and reproductive tissue in ovariectomized rats","volume":"2012","author":"Xue","year":"2012","journal-title":"Evid.-Based Complement. Altern."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.jep.2008.04.009","article-title":"Antiosteoporotic chemical constituents from Er-Xian Decoction, a traditional Chinese herbal formula","volume":"118","author":"Qin","year":"2008","journal-title":"J. Ethnopharmacol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.jep.2006.04.020","article-title":"Antiosteoporotic activity of Er-Xian Decoction, a traditional Chinese herbal formula, in ovariectomized rats","volume":"108","author":"Nian","year":"2006","journal-title":"J. Ethnopharmacol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.jchromb.2007.10.019","article-title":"Simultaneous determination of icariin, icariside II and osthole in rat plasma after oral administration of the extract of Gushudan (a Chinese compound formulation) by LC-MS\/MS","volume":"860","author":"Liu","year":"2007","journal-title":"J. Chromatogr. B"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1016\/j.jep.2004.09.038","article-title":"Stimulative effects of Drynariae Rhizoma extracts on the proliferation and differentiation of osteoblastic MC3T3-E1 cells","volume":"96","author":"Jeong","year":"2005","journal-title":"J. Ethnopharmacol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/j.jep.2004.09.039","article-title":"Anti-bone resorption activity of deer antler aqua-acupunture, the pilose antler of Cervus korean TEMMINCK var. mantchuricus Swinhoe (Nokyong) in adjuvant-induced arthritic rats","volume":"96","author":"Kim","year":"2005","journal-title":"J. Ethnopharmacol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.jep.2007.04.020","article-title":"Chloroform extract of deer antler inhibits osteoclast differentiation and bone resorption","volume":"113","author":"Li","year":"2007","journal-title":"J. Ethnopharmacol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1271\/bbb.63.905","article-title":"Enhancing effect of dietary vinegar on the intestinal absorbtion of calcium in ovariectomized rats","volume":"63","author":"Mikiya","year":"1999","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1056\/NEJM199709043371003","article-title":"Effect of calcium and vitamin D supplementation on bone density in men and women 65 years of age or older","volume":"337","author":"Harris","year":"1997","journal-title":"N. Engl. J. Med."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.1056\/NEJM199212033272305","article-title":"Vitamin D3 and calcium to prevent hip fractures in elderly women","volume":"327","author":"Chapuy","year":"1992","journal-title":"N. Engl. J. Med."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1007\/s007760100059","article-title":"Effect of exercise training and detraining on bone mineral density in postmenopausal women with osteoporosis","volume":"6","author":"Iwamoto","year":"2001","journal-title":"J. Orthop. Sci."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1294","DOI":"10.1139\/apnm-2014-0060","article-title":"1H NMR analysis of the human urinary metabolome in response to an 18-month multi-component exercise program and calcium-vitamin-D3 supplementation in older men","volume":"39","author":"Sheedy","year":"2014","journal-title":"Appl. Physiol. Nutr. Metab."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1210\/jc.2010-2284","article-title":"Independent and combined effects of calcium-vitamin D3 and exercise on bone structure and strength in older men: An 18-month factorial design randomized controlled trial","volume":"96","author":"Kukuljan","year":"2011","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1007\/s00198-008-0776-y","article-title":"Effects of a multi-component exercise program and calcium-vitamin-D3-fortified milk on bone mineral density in older men: A randomised controlled trial","volume":"20","author":"Kukuljan","year":"2009","journal-title":"Osteoporos. Int."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1093\/bib\/bbm030","article-title":"Current progress in computational metabolomics","volume":"8","author":"Wishart","year":"2007","journal-title":"Brief Bioinform."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"E904","DOI":"10.1152\/ajpendo.90248.2008","article-title":"Mechanisms of antidiabetogenic and body weight-lowering effects of estrogen in high-fat diet-fed mice","volume":"295","author":"Bryzgalova","year":"2008","journal-title":"Am. J. Physiol.-Endocrinol. Metab."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1097\/gme.0b013e31823a40d9","article-title":"Glucosamine-induced insulin resistance in ovariectomized rats is relevant to decreasing the expression of glucose transport protein subtype 4 in the skeletal muscle and in increasing the size of pancreatic islets","volume":"19","author":"Kang","year":"2012","journal-title":"Menopause"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"453","DOI":"10.3109\/13697137.2010.539723","article-title":"Glucose tolerance of premenopausal women after menopause due to surgical removal of ovaries","volume":"14","author":"Pirimoglu","year":"2011","journal-title":"Climacteric"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.abb.2010.07.030","article-title":"Bone and glucose metabolism: A two-way street","volume":"503","author":"Motyl","year":"2010","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"S14","DOI":"10.1038\/ki.2011.25","article-title":"Bone: From a reservoir of minerals to a regulator of energy metabolism","volume":"79","author":"Confavreux","year":"2011","journal-title":"Kidney Int."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1016\/j.coph.2004.03.002","article-title":"Controlling the balance between osteoblastogenesis and adipogenesis and the consequent therapeutic implications","volume":"4","author":"Nuttall","year":"2004","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1507\/endocrj.49.211","article-title":"Plasma lipids and osteoporosis in postmenopausal women","volume":"49","author":"Yamaguchi","year":"2002","journal-title":"Endocr. J."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"5929","DOI":"10.1016\/j.febslet.2007.11.035","article-title":"Taurine increases cell proliferation and generates an increase in [Mg2+]i accompanied by ERK 1\/2 activation in human osteoblast cells","volume":"581","author":"Jeon","year":"2007","journal-title":"FEBS Lett."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.tem.2014.11.004","article-title":"Effects of the gut microbiota on bone mass","volume":"26","author":"Ohlsson","year":"2015","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1002\/jbmr.2765","article-title":"The microbiome and musculoskeletal conditions of aging: A review of evidence for impact and potential therapeutics","volume":"31","author":"Steves","year":"2016","journal-title":"J. Bone Miner. Res."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1002\/jbmr.1588","article-title":"The gut microbiota regulates bone mass in mice","volume":"27","author":"Sjogren","year":"2012","journal-title":"J. Bone Miner. Res."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1829","DOI":"10.1002\/jbmr.403","article-title":"Effects of denosumab on fracture and bone mineral density by level of kidney function","volume":"26","author":"Jamal","year":"2011","journal-title":"J. Bone Miner. Res."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1016\/j.talanta.2010.09.026","article-title":"Metabonomic study on 'Kidney-Yang Deficiency syndrome' and intervention effects of Rhizoma Drynariae extracts in rats using ultra performance liquid chromatography coupled with mass spectrometry","volume":"83","author":"Lu","year":"2011","journal-title":"Talanta"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1136\/bmj.38975.390370.7C","article-title":"How to measure renal function in clinical practice","volume":"7571","author":"Traynor","year":"2006","journal-title":"Br. Med. J."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/S0272-6386(12)80168-5","article-title":"Chronic renal failure secondary to 2,8-dihydroxyadenine deposition: The first report of recurrence in a kidney transplant","volume":"24","author":"Deland","year":"1994","journal-title":"Am. J. Kidney Dis."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1359\/jbmr.2000.15.2.315","article-title":"Early postmenopausal bone loss is associated with PvuII estrogen receptor gene polymorphism in Finnish women: Effect of hormone replacement therapy","volume":"15","author":"Heikkinen","year":"2000","journal-title":"J. Bone Miner. Res."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1007\/s001980170070","article-title":"A simple tool to identify Asian women at increased risk of osteoporosis","volume":"12","author":"Koh","year":"2001","journal-title":"Osteoporos. Int."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1007\/BF01880413","article-title":"The contribution of bone loss to postmenopausal osteoporosis","volume":"1","author":"Hui","year":"1990","journal-title":"Osteoporos. Int."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1002\/mas.20338","article-title":"Applications of mass spectrometry to metabolomics and metabonomics: Detection of biomarkers of aging and of age-related diseases","volume":"31","author":"Mishur","year":"2012","journal-title":"Mass Spectrom. Rev."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.aca.2009.11.042","article-title":"Chemometrics in metabolomics-a review in human disease diagnosis","volume":"659","author":"Madsen","year":"2010","journal-title":"Anal. Chim. Acta"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1458","DOI":"10.1359\/jbmr.1998.13.9.1458","article-title":"Bone loss, physical activity, and weight change in elderly women: The Dubbo osteoporosis epidemiology study","volume":"13","author":"Nguyen","year":"1998","journal-title":"J. Bone Miner. Res."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1111\/j.1471-0528.2006.01150.x","article-title":"The use of high-dimensional biology (genomics, transcriptomics, proteomics, and metabolomics) to understand the preterm parturition syndrome","volume":"113","author":"Romero","year":"2006","journal-title":"BJOG-Int. J. Obstet. Gynaecol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.aca.2012.05.049","article-title":"NMR and pattern recognition methods in metabolomics: From data acquisition to biomarker discovery: A review","volume":"750","author":"Smolinska","year":"2012","journal-title":"Anal. Chim. Acta"},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Shum, L.C., White, N.S., Nadtochiy, S.M., Bentley, K.L., Brookes, P.S., Jonason, J.H., and Eliseev, R.A. (2016). Cyclophilin D knock-out mice show enhanced resistance to osteoporosis and to metabolic changes observed in aging bone. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0155709"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1017\/S0007114510003065","article-title":"Genomic and metabolomic patterns segregate with responses to calcium and vitamin D supplementation","volume":"105","author":"Elnenaei","year":"2011","journal-title":"Br. J. Nutr."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1576\/toag.13.3.189.27672","article-title":"\u2018Omic\u2019 technologies: Genomics, transcriptomics, proteomics and metabolomics","volume":"13","author":"Horgan","year":"2011","journal-title":"Obstet. Gynaecol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1080\/14737159.2016.1198258","article-title":"Transcriptomics, proteomics and metabolomics driven biomarker discovery in COPD: An update","volume":"16","author":"Ghosh","year":"2016","journal-title":"Expert Rev. Mol. Diagn."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/17\/12\/2018\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T19:27:55Z","timestamp":1760210875000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/17\/12\/2018"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,12,2]]},"references-count":101,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2016,12]]}},"alternative-id":["ijms17122018"],"URL":"https:\/\/doi.org\/10.3390\/ijms17122018","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,12,2]]}}}