ArticleJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research2021
Metabolomics Insights into Osteoporosis Through Association With Bone Mineral Density.
Article in Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 3 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
44 citing papers in PubMed, 3 syntheses or guidelines pooled it, 68 citations in OpenAlex.
- Distinct Metabolites in Osteopenia and Osteoporosis: A Systematic Review and Meta-Analysis.Nutrients · 2023Pooled it
- Low Circulating Valine Associate With High Risk of Hip Fractures.The Journal of clinical endocrinology and metabolism · 2023Pooled it
- Metabolomics of Osteoporosis in Humans: A Systematic Review.Current osteoporosis reports · 2023Pooled it
- Baseline serum metabolites predict fractures in individuals who were Black and had type 2 diabetes.Frontiers in endocrinology · 2026Trial
- Article
- Causal effects among hypertension, osteoporosis, and metabolites: A Mendelian randomization study.Journal of the Chinese Medical Association : JCMA · 2026Article
- Regulating Glucose Metabolism Enzymes for Osteoporosis Therapy: Current and Future Approaches.International journal of molecular sciences · 2026Review
- Plasma metabolomic profiles and risk of hip fracture among US individuals: a nested case-control and prospective cohort study.EBioMedicine · 2026Article
- Integrative Harmonization of Phenotypic and Genomic Data Improves Bone Mineral Density Prediction in Multi-Study Osteoporosis Research.Genetic epidemiology · 2026Article
- Prevalence of low bone mineral density and associated plasma metabolite alterations in thalassemia.Scientific reports · 2026Article
- Associations of Dietary and Circulating Choline and Glycine With Bone Mineral Density: UK Biobank Analyses With Mendelian Randomization.International journal of endocrinology · 2026Article
- A machine-learning-based osteoporosis screening tool integrating the Shapley Additive exPlanation (SHAP) method: model development and validation study.Archives of osteoporosis · 2025Article
- Emerging applications of feature selection in osteoporosis research: from biomarker discovery to clinical decision support.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2025Review
- Role of amino acid metabolism in osteoporosis: Effects on the bone microenvironment and treatment strategies (Review).Molecular medicine reports · 2025Review
- Metabolomic evaluation of air pollution-related bone damage and potential mediation in Women's Health Initiative participants.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2025Article
- Current cutting-edge omics techniques on musculoskeletal tissues and diseases.Bone research · 2025Review
- Causal Relationship Between Blood Metabolites and Osteoporosis: A Two-Sample Mendelian Randomization and Genetic Correlation Analysis.Bioengineering (Basel, Switzerland) · 2025Article
- Combining untargeted and targeted metabolomic profiling reveals principal differences between osteopenia, Osteoporosis and healthy controls.Aging clinical and experimental research · 2025Article
- [Moxibustion Inhibits Postmenopausal Bone Loss by Regulating the Metabolism of Gut Microbiota-Related Serotonin].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2025Article
- ALG5 downregulation inhibits osteogenesis and promotes adipogenesis by regulating the N-glycosylation of SLC6A9 in osteoporosis.Cellular and molecular life sciences : CMLS · 2025Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Osteoporosis, 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).
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.