Mangano Kelsey M, Noel Sabrina E, Lai Chao-Qiang, Christensen Jacob J, Ordovas Jose M, Dawson-Hughes Bess, Tucker Katherine L, Parnell Laurence D
Department of Biomedical and Nutritional Sciences and Center for Population Health, University of Massachusetts Lowell, 3 Solomont Way, 01854 Lowell, MA, USA.
Department of Biomedical and Nutritional Sciences and Center for Population Health, University of Massachusetts Lowell, 3 Solomont Way, 01854 Lowell, MA, USA.
Bone. 2021 Mar;144:115780. doi: 10.1016/j.bone.2020.115780. Epub 2020 Dec 2.
The impact of nutrition on the metabolic profile of osteoporosis (OS) is unknown.
Identify biochemical factors driving the association of fruit and vegetable (FV) intakes with OS prevalence using an untargeted metabolomics approach.
Cross-sectional dietary, anthropometric and plasma metabolite data were examined from the Boston Puerto Rican Osteoporosis Study, n = 600 (46-79 yr).
Bone mineral density was assessed by DXA. OS was defined by clinical standards. A culturally adapted FFQ assessed usual dietary intake. Principal components analysis (PCA) of 42 FV items created 6 factors. Metabolomic profiles derived from plasma samples were assessed on a commercial platform. Differences in levels of 525 plasma metabolites between disease groups (OS vs no-OS) were compared using logistic regression; and associations with FV intakes by multivariable linear regression, adjusted for covariates. Metabolites significantly associated with OS status or with total FV intake were analyzed for enrichment in various biological pathways using Mbrole 2.0, MetaboAnalyst, and Reactome, using FDR correction of P-values. Correlation coefficients were calculated as Spearman's rho rank correlations, followed by hierarchical clustering of the resulting correlation coefficients using PCA FV factors and sex-specific sets of OS-associated metabolites.
High FV intake was inversely related to OS prevalence (Odds Ratio = 0.73; 95% CI = 0.57, 0.94; P = 0.01). Several biological processes affiliated with the FV-associating metabolites, including caffeine metabolism, carnitines and fatty acids, and glycerophospholipids. Important processes identified with OS-associated metabolites were steroid hormone biosynthesis in women and branched-chain amino acid metabolism in men. Factors derived from PCA were correlated with the OS-associated metabolites, with high intake of dark leafy greens and berries/melons appearing protective in both sexes.
These data warrant investigation into whether increasing intakes of dark leafy greens, berries and melons causally affect bone turnover and BMD among middle-aged and older adults at risk for osteoporosis via sex-specific metabolic pathways, and how gene-diet interactions alter these sex-specific metabolomic-osteoporosis links. ClinicalTrials.gov Identifier: NCT01231958.
营养对骨质疏松症（OS）代谢谱的影响尚不清楚。
采用非靶向代谢组学方法，确定驱动水果和蔬菜（FV）摄入量与OS患病率之间关联的生化因素。
对波士顿波多黎各骨质疏松症研究中的横断面饮食、人体测量和血浆代谢物数据进行了检查，样本量n = 600（46 - 79岁）。
通过双能X线吸收法（DXA）评估骨密度。根据临床标准定义OS。采用文化适应性食物频率问卷（FFQ）评估日常饮食摄入量。对42种FV项目进行主成分分析（PCA），生成6个因子。在商业平台上评估血浆样本的代谢组学谱。使用逻辑回归比较疾病组（OS组与非OS组）之间525种血浆代谢物水平的差异；并通过多变量线性回归分析与FV摄入量的关联，对协变量进行校正。使用Mbrole 2.0、MetaboAnalyst和Reactome，对与OS状态或总FV摄入量显著相关的代谢物进行分析，以确定其在各种生物途径中的富集情况，并对P值进行错误发现率（FDR）校正。计算相关系数为斯皮尔曼等级相关系数，然后使用PCA FV因子和特定性别的OS相关代谢物集对所得相关系数进行层次聚类。
高FV摄入量与OS患病率呈负相关（优势比 = 0.73；95%置信区间 = 0.57, 0.94；P = 0.01）。与FV相关代谢物相关的几个生物过程，包括咖啡因代谢、肉碱和脂肪酸以及甘油磷脂。与OS相关代谢物确定的重要过程在女性中是类固醇激素生物合成，在男性中是支链氨基酸代谢。PCA得出的因子与OS相关代谢物相关，高摄入深色绿叶蔬菜和浆果/甜瓜对两性均有保护作用。
这些数据值得研究增加深色绿叶蔬菜、浆果和甜瓜的摄入量是否通过特定性别的代谢途径对有骨质疏松症风险的中老年人的骨转换和骨密度产生因果影响，以及基因 - 饮食相互作用如何改变这些特定性别的代谢组学 - 骨质疏松症联系。临床试验注册号：NCT01231958。
