Abstract
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 (p < 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 (p < 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 (p < 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.
Highlights
Bone is a dynamic tissue that is continually resorbed and formed through a process called remodeling [1,2]
P1NP was predominantly related to amino acid and B vitamin metabolism, whereas CTX was associated with lipid-related pathways and fat-soluble vitamin metabolism, including vitamin D and vitamin E
Our study identified distinct energy-yielding metabolic pathways associated with the surrogate markers of bone formation (P1NP) and bone resorption (CTX)
Summary
Bone is a dynamic tissue that is continually resorbed and formed through a process called remodeling [1,2]. Through the coordinated activities of bone-forming osteoblasts and bone-resorbing osteoclasts, adult bone mass is maintained at a relatively constant state until the rate of resorption outpaces that of formation [1,3]. This shift typically begins after attainment of peak bone mass around the age of 30 years and results in a gradual decline in bone mass from that point [4]. Preventing the progression of bone mass loss to osteoporosis is a public health priority because osteoporosis leads to a diminished quality of life coupled with disability and morbidity [5,6]. The metabolic activity of bone can be monitored by measuring the serum levels of bone turnover markers (BTMs) [7].
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