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Article: Metabolomics Insights into Osteoporosis Through Association With Bone Mineral Density

TitleMetabolomics Insights into Osteoporosis Through Association With Bone Mineral Density
Authors
KeywordsDXA
FRACTURE RISK ASSESSMENT METABOLOMICS
GENERAL POPULATION STUDIES
OSTEOPOROSIS
Issue Date2021
PublisherWiley-Blackwell Publishing, Inc. The Journal's web site is located at http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1523-4681
Citation
Journal of Bone and Mineral Research, 2021, v. 36 n. 4, p. 729-738 How to Cite?
AbstractOsteoporosis, a disease characterized by low bone mineral density (BMD), increases the risk for fractures. Conventional risk factors alone do not completely explain measured BMD or osteoporotic fracture risk. Metabolomics may provide additional information. We aim to identify BMD-associated metabolomic markers that are predictive of fracture risk. We assessed 209 plasma metabolites by liquid chromatography with tandem mass spectrometry (LC–MS/MS) in 1552 Framingham Offspring Study participants, and measured femoral neck (FN) and lumbar spine (LS) BMD 2 to 10 years later using dual-energy X-ray absorptiometry. We assessed osteoporotic fractures up to 27-year follow-up after metabolomic profiling. We identified 27 metabolites associated with FN-BMD or LS-BMD by LASSO regression with internal validation. Incorporating selected metabolites significantly improved the prediction and the classification of osteoporotic fracture risk beyond conventional risk factors (area under the curve [AUC] = 0.74 for the model with identified metabolites and risk factors versus AUC = 0.70 with risk factors alone, p = .001; net reclassification index = 0.07, p = .03). We replicated significant improvement in fracture prediction by incorporating selected metabolites in 634 participants from the Hong Kong Osteoporosis Study (HKOS). The glycine, serine, and threonine metabolism pathway (including four identified metabolites: creatine, dimethylglycine, glycine, and serine) was significantly enriched (false discovery rate [FDR] p value = .028). Furthermore, three causally related metabolites (glycine, phosphatidylcholine [PC], and triacylglycerol [TAG]) were negatively associated with FN-BMD, whereas PC and TAG were negatively associated with LS-BMD through Mendelian randomization analysis. In summary, metabolites associated with BMD are helpful in osteoporotic fracture risk prediction. Potential causal mechanisms explaining the three metabolites on BMD are worthy of further experimental validation. Our findings may provide novel insights into the pathogenesis of osteoporosis. © 2021 American Society for Bone and Mineral Research (ASBMR).
Persistent Identifierhttp://hdl.handle.net/10722/304742
ISSN
2023 Impact Factor: 5.1
2023 SCImago Journal Rankings: 1.868
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorZhang, X-
dc.contributor.authorXu, H-
dc.contributor.authorLi, GHY-
dc.contributor.authorLong, MT-
dc.contributor.authorCheung, CL-
dc.contributor.authorVasan, RS-
dc.contributor.authorHsu, YH-
dc.contributor.authorKiel, DP-
dc.contributor.authorLiu, CT-
dc.date.accessioned2021-10-05T02:34:31Z-
dc.date.available2021-10-05T02:34:31Z-
dc.date.issued2021-
dc.identifier.citationJournal of Bone and Mineral Research, 2021, v. 36 n. 4, p. 729-738-
dc.identifier.issn0884-0431-
dc.identifier.urihttp://hdl.handle.net/10722/304742-
dc.description.abstractOsteoporosis, a disease characterized by low bone mineral density (BMD), increases the risk for fractures. Conventional risk factors alone do not completely explain measured BMD or osteoporotic fracture risk. Metabolomics may provide additional information. We aim to identify BMD-associated metabolomic markers that are predictive of fracture risk. We assessed 209 plasma metabolites by liquid chromatography with tandem mass spectrometry (LC–MS/MS) in 1552 Framingham Offspring Study participants, and measured femoral neck (FN) and lumbar spine (LS) BMD 2 to 10 years later using dual-energy X-ray absorptiometry. We assessed osteoporotic fractures up to 27-year follow-up after metabolomic profiling. We identified 27 metabolites associated with FN-BMD or LS-BMD by LASSO regression with internal validation. Incorporating selected metabolites significantly improved the prediction and the classification of osteoporotic fracture risk beyond conventional risk factors (area under the curve [AUC] = 0.74 for the model with identified metabolites and risk factors versus AUC = 0.70 with risk factors alone, p = .001; net reclassification index = 0.07, p = .03). We replicated significant improvement in fracture prediction by incorporating selected metabolites in 634 participants from the Hong Kong Osteoporosis Study (HKOS). The glycine, serine, and threonine metabolism pathway (including four identified metabolites: creatine, dimethylglycine, glycine, and serine) was significantly enriched (false discovery rate [FDR] p value = .028). Furthermore, three causally related metabolites (glycine, phosphatidylcholine [PC], and triacylglycerol [TAG]) were negatively associated with FN-BMD, whereas PC and TAG were negatively associated with LS-BMD through Mendelian randomization analysis. In summary, metabolites associated with BMD are helpful in osteoporotic fracture risk prediction. Potential causal mechanisms explaining the three metabolites on BMD are worthy of further experimental validation. Our findings may provide novel insights into the pathogenesis of osteoporosis. © 2021 American Society for Bone and Mineral Research (ASBMR).-
dc.languageeng-
dc.publisherWiley-Blackwell Publishing, Inc. The Journal's web site is located at http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1523-4681-
dc.relation.ispartofJournal of Bone and Mineral Research-
dc.rightsSubmitted (preprint) Version This is the pre-peer reviewed version of the following article: [FULL CITE], which has been published in final form at [Link to final article using the DOI]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. Accepted (peer-reviewed) Version This is the peer reviewed version of the following article: [FULL CITE], which has been published in final form at [Link to final article using the DOI]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.-
dc.subjectDXA-
dc.subjectFRACTURE RISK ASSESSMENT METABOLOMICS-
dc.subjectGENERAL POPULATION STUDIES-
dc.subjectOSTEOPOROSIS-
dc.titleMetabolomics Insights into Osteoporosis Through Association With Bone Mineral Density-
dc.typeArticle-
dc.identifier.emailCheung, CL: lung1212@hku.hk-
dc.identifier.authorityCheung, CL=rp01749-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1002/jbmr.4240-
dc.identifier.pmid33434288-
dc.identifier.pmcidPMC8488880-
dc.identifier.scopuseid_2-s2.0-85100136113-
dc.identifier.hkuros325797-
dc.identifier.volume36-
dc.identifier.issue4-
dc.identifier.spage729-
dc.identifier.epage738-
dc.identifier.isiWOS:000613825400001-
dc.publisher.placeUnited States-

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