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Conceptualization, M.P.B. and J.L.R.; methodology, M.P.B., J.L.R., K.H.L., D.P.J., J.A.A.; software, M.P.B., J.L.R., K.R.T., K.U.; formal analysis, M.P.B., J.L.R., K.L.T., K.U.; investigation, M.P.B., J.L.R., H.D., T.R.Z., J.A.A.; resources, M.P.B., J.L.R., D.P.J., H.D., T.R.Z., J.A.A.; data curation, M.P.B, J.L.R., J.A.A.; writing—original draft preparation, M.P.B., J.L.R.; writing—review and editing, M.N.W., R.P., H.D., T.R.Z., J.A.A.; supervision, D.P.J., H.D., T.R.Z., J.A.A.; funding acquisition, M.P.B., J.L.R., H.D., T.R.Z., J.A.A. All authors have read and agreed to the published version of the manuscript.

We gratefully acknowledge the research volunteers, faculty and staff of the Emory Clinical Biomarkers Laboratory, and nurses and staff of the Georgia CTSA Clinical Research Unit at Emory University Hospital.

The authors declare no conflict of interest.


Research Funding:

This research was supported by funding from the National Institutes of Health (NIH) R03 AG066559 (J.A.A., M.N.W.), U54 AG062334 (Emory Specialized Center of Research Excellence on Sex Differences, J.A.A., M.N.W.), K24 DK096574 (T.R.Z.), P30 ES019776 (D.P.J., T.R.Z.), R01 DK112946 (R.P.), R01 DK108842 (R.P.), R01 AR068157 (M.N.W.), R01 AR070091 (M.N.W.), R21 AG065977 (H.D.), and the Georgia Clinical and Translational Science Alliance (UL1 TR002378). M.N.W. was also supported by a grant from the Biomedical Laboratory Research and Development Service of the VA Office of Research and Development (5I01BX000105).


  • bone
  • metabolism
  • microbiome
  • nutrition
  • osteoclast
  • osteoblast

Metabolomic Associations with Serum Bone Turnover Markers

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Journal Title:



Volume 12, Number 10


Type of Work:

Article | Final Publisher PDF


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.

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© 2020 by the authors.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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