背景:很少评估代谢物对骨脆性的潜在联合影响。我们评估了血浆代谢模式与骨脆性终点的关联(主要是,骨质疏松相关骨折,and,其次,Hortega研究参与者的骨密度BMD)。氧化还原平衡在骨代谢中起关键作用。我们还通过氧化还原相关金属暴露水平和候选遗传变异评估了参与者亚组的差异关联。
方法:在来自Hortega研究的467名年龄超过50岁的参与者中,来自西班牙一个地区的代表性样本,我们从核磁共振光谱中估计了54种血浆代谢物的代谢主成分(mPC)。通过AAS在血浆中和通过HPLC-ICPMS在尿液中测量金属生物标志物。通过寡核苷酸连接测定测量氧化还原相关SNP(N=341)。
结果:对于mPC1(非必需和必需氨基酸,包括支链,和细菌共代谢产物,包括异丁酸,三甲胺和丙酸苯酯,相对于脂肪酸和VLDL)和mPC4(HDL),但mPC2(必需氨基酸,包括芳香,和细菌共代谢产物,包括异丙醇和甲醇)。BMD模型的结果是一致的。硒减少和锑增加的参与者,砷和,暗示性地,镉暴露显示mPC2相关骨折风险较高。19个基因的遗传变异,关于NCF4,NOX4和XDH的最有力证据,表现出不同的代谢相关骨折风险。
结论:反映氨基酸的代谢模式,微生物群共代谢和脂质代谢与骨脆性终点相关。氧化还原相关变体的载体可能受益于代谢干预,以防止骨骼脆性的后果,这取决于它们的锑,砷,硒,and,可能,镉,暴露水平。
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.
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.
Redox-related SNPs (N = 341) were measured by oligo-ligation assay.
The prospective association with incident bone fractures was inverse for mPC1 (non-essential and essential 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.
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.