Metabolomic Associations with Serum Bone Turnover Markers

• Published in: Nutrients 2020-10, Vol.12 (10), p.3161
• Main Authors: Bellissimo, Moriah P, Roberts, Joseph L, Jones, Dean P, Liu, Ken H, Taibl, Kaitlin R, Uppal, Karan, Weitzmann, M Neale, Pacifici, Roberto, Drissi, Hicham, Ziegler, Thomas R, Alvarez, Jessica A
• Format: Article
• Language: English
• Subjects: Acids; Adult; Adults; Aging; Ascorbic acid; Bile Acids and Salts - metabolism; Biomarkers; Biomarkers - blood; Biosynthesis; Body composition; bone; Bone growth; Bone remodeling; Bone Remodeling - physiology; Bone resorption; Bone turnover; Carbohydrate metabolism; Carbohydrates; Chromatography; Collagen; Collagen (type I); Collagen Type I - blood; Column chromatography; Fasting; Female; Gastrointestinal Microbiome - physiology; Health care; Humans; Intestinal microflora; Laboratories; Lipids; Liquid chromatography; Male; Markers; Mass spectrometry; Mass spectroscopy; Metabolic pathways; Metabolism; Metabolites; Metabolome; Metabolomics; Metropolitan areas; microbiome; Microbiota; Micronutrients - metabolism; Nutrition; Nutritional Physiological Phenomena - physiology; osteoblast; Osteoblasts; osteoclast; Osteoclasts; Osteogenesis; Osteogenesis - physiology; Osteoporosis; Oxidation; Particle size; Peptide Fragments - blood; Peptides - blood; Plasma; Procollagen; Procollagen - blood; Proline; Pyruvic acid; Therapeutic applications; Tricarboxylic acid cycle; Vitamin D; Vitamin E; Vitamins; Vitamins - metabolism
• ISSN: 2072-6643; 2072-6643
• DOI: 10.3390/nu12103161

Bone is a dynamic tissue that is in a constant state of remodeling. Bone turnover markers (BTMs), procollagen type I N-terminal propeptide (P1NP) and C-terminal telopeptides of type I collagen (CTX), provide sensitive measures of bone formation and resorption, respectively. This study used ultra-high-resolution metabolomics (HRM) to determine plasma metabolic pathways and targeted metabolites related to the markers of bone resorption and formation in adults. This cross-sectional clinical study included 34 adults (19 females, mean 27.8 years), without reported illnesses, recruited from a US metropolitan area. Serum BTM levels were quantified by an ELISA. Plasma HRM utilized dual-column liquid chromatography and mass spectrometry to identify metabolites and metabolic pathways associated with BTMs. Metabolites significantly associated with P1NP ( < 0.05) were significantly enriched in pathways linked to the TCA cycle, pyruvate metabolism, and metabolism of B vitamins important for energy production (e.g., niacin, thiamin). Other nutrition-related metabolic pathways associated with P1NP were amino acid (proline, arginine, glutamate) and vitamin C metabolism, which are important for collagen formation. Metabolites associated with CTX levels ( < 0.05) were enriched within lipid and fatty acid beta-oxidation metabolic pathways, as well as fat-soluble micronutrient pathways including, vitamin D metabolism, vitamin E metabolism, and bile acid biosynthesis. P1NP and CTX were significantly related to microbiome-related metabolites ( < 0.05). Macronutrient-related pathways including lipid, carbohydrate, and amino acid metabolism, as well as several gut microbiome-derived metabolites were significantly related to BTMs. Future research should compare metabolism BTMs relationships reported here to aging and clinical populations to inform targeted therapeutic interventions.