RT info:eu-repo/semantics/article
T1 Metabolomic patterns, redox-related genes and metals, and bone fragility endpoints in the Hortega Study
A1 Pérez Castrillon, José Luis
K1 Endocrinologia y Metabolismo
K1 Metabolomics, Bone mineral density, Osteoporosis-related bone fractures, Candidate genes, Metals
AB A B S T R A C TBackground: The potential joint influence of metabolites on bone fragility has been rarely evaluated. We assessed the association of plasma metabolic patterns with bone fragility endpoints (primarily, incident osteoporosis related bone fractures, and, secondarily, bone mineral density BMD) in the Hortega Study participants. Redox balance plays a key role in bone metabolism. We also assessed differential associations in participant subgroups by redox-related metal exposure levels and candidate genetic variants.Material and methods: In 467 participants older than 50 years from the Hortega Study, a representative sample from a region in Spain, we estimated metabolic principal components (mPC) for 54 plasma metabolites from NMR-spectrometry. Metals biomarkers were measured in plasma by AAS and in urine by HPLC-ICPMS. Redoxrelated SNPs (N = 341) were measured by oligo-ligation assay.Results: The prospective association with incident bone fractures was inverse for mPC1 (non-essential andessential amino acids, including branched-chain, and bacterial co-metabolites, including isobutyrate, trimethylamines and phenylpropionate, versus fatty acids and VLDL) and mPC4 (HDL), but positive for mPC2 (essential amino acids, including aromatic, and bacterial co-metabolites, including isopropanol and methanol). Findings from BMD models were consistent. Participants with decreased selenium and increased antimony, arsenic and, suggestively, cadmium exposures showed higher mPC2-associated bone fractures risk. Genetic variants annotated to 19 genes, with the strongest evidence for NCF4, NOX4 and XDH, showed differential metabolic-related bone fractures risk.Conclusions: Metabolic patterns reflecting amino acids, microbiota co-metabolism and lipid metabolism were associated with bone fragility endpoints. Carriers of redox-related variants may benefit from metabolic interventions to prevent the consequences of bone fragility depending on their antimony, arsenic, selenium, and, possibly, cadmium, exposure levels.
PB Elsevier
SN 0891-5849
YR 2023
FD 2023
LK https://uvadoc.uva.es/handle/10324/64700
UL https://uvadoc.uva.es/handle/10324/64700
LA eng
NO Free Radical Biology and Medicine 2023; 194: 52–61
NO Producción Científica
DS UVaDOC
RD 13-jul-2024