ArticleJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research2018
Metabolomic Pathways to Osteoporosis in Middle-Aged Women: A Genome-Metabolome-Wide Mendelian Randomization Study.
Article in Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 2 of them syntheses that pooled it.
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Who cites it
40 citing papers in PubMed, 2 syntheses or guidelines pooled it, 60 citations in OpenAlex.
- Low Circulating Valine Associate With High Risk of Hip Fractures.The Journal of clinical endocrinology and metabolism · 2023Pooled it
- Metabolomic biomarkers of low BMD: a systematic review.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2021Pooled it
- Genetically predicted ZDHHC8 expression and osteoporosis risk: A two-sample Mendelian randomization and metabolite mediation study.Medicine · 2026Article
- Article
- Plasma metabolomic profiles and risk of hip fracture among US individuals: a nested case-control and prospective cohort study.EBioMedicine · 2026Article
- Associations of Dietary and Circulating Choline and Glycine With Bone Mineral Density: UK Biobank Analyses With Mendelian Randomization.International journal of endocrinology · 2026Article
- Causal Relationship Between Blood Metabolites and Osteoporosis: A Two-Sample Mendelian Randomization and Genetic Correlation Analysis.Bioengineering (Basel, Switzerland) · 2025Article
- Association of genetically predicted blood metabolites with osteopenia in individuals over 60 years of age: A Mendelian randomization study.Joint diseases and related surgery · 2025Article
- Metabolism and metabolomics in senescence, aging, and age-related diseases: a multiscale perspective.Frontiers of medicine · 2025Review
- Multi-scale variational autoencoder for imputation of missing values in untargeted metabolomics using whole-genome sequencing data.Computers in biology and medicine · 2024Article
- Causal relationship between Interleukin-27 expression levels and osteoporosis: a bidirectional mendelian randomization study.BMC musculoskeletal disorders · 2024Article
- Causal Association between Circulating Metabolites and Dementia: A Mendelian Randomization Study.Nutrients · 2024Article
- Unraveling the Evolutionary Diet Mismatch and Its Contribution to the Deterioration of Body Composition.Metabolites · 2024Review
- Article
- Genetically predicted elevated circulating 3,4-dihydroxybutyrate levels mediate the association between family Christensenellaceae and osteoporosis risk: a Mendelian randomization study.Frontiers in endocrinology · 2024Article
- Gut microbiota, plasma metabolites, and osteoporosis: unraveling links via Mendelian randomization.Frontiers in microbiology · 2024Article
- Early changes of bone metabolites and lymphocyte subsets may participate in osteoporosis onset: a preliminary study of a postmenopausal osteoporosis mouse model.Frontiers in endocrinology · 2024Article
- Mendelian Randomization Study of Lipid Metabolites Reveals Causal Associations with Heel Bone Mineral Density.Nutrients · 2023Article
- Characterisation of Fasting and Postprandial NMR Metabolites: Insights from the ZOE PREDICT 1 Study.Nutrients · 2023Article
- Metabolome-Wide Mendelian Randomization Assessing the Causal Relationship Between Blood Metabolites and Bone Mineral Density.Calcified tissue international · 2023Article
Corrections and comments
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Authors and funding
10 authors at 7 institutions in 5 countries.
Funding
Abstract
The metabolic state of the body can be a major determinant of bone health. We used a Mendelian randomization approach to identify metabolites causally associated with bone mass to better understand the biological mechanisms of osteoporosis. We tested bone phenotypes (femoral neck, total hip, and lumbar spine bone mineral density [BMD]) for association with 280 fasting blood metabolites in 6055 women from TwinsUK cohort with genomewide genotyping scans. Causal associations between metabolites and bone phenotypes were further assessed in a bidirectional Mendelian randomization study using genetic markers/scores as instrumental variables. Significant associations were replicated in 624 participants from the Hong Kong Osteoporosis Study (HKOS). Fifteen metabolites showed direct associations with bone phenotypes after adjusting for covariates and multiple testing. Using genetic instruments, four of these metabolites were found to be causally associated with hip or spine BMD. These included androsterone sulfate, epiandrosterone sulfate, 5alpha-androstan-3beta17beta-diol disulfate (encoded by CYP3A5), and 4-androsten-3beta17beta-diol disulfate (encoded by SULT2A1). In the HKOS population, all four metabolites showed significant associations with hip and spine BMD in the expected directions. No causal reverse association between BMD and any of the metabolites were found. In the first metabolome-genomewide Mendelian randomization study of human bone mineral density, we identified four novel biomarkers causally associated with BMD. Our findings reveal novel biological pathways involved in the pathogenesis of osteoporosis. © 2017 American Society for Bone and Mineral Research.
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