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Metabolomic biomarkers of low BMD: a systematic review

Abstract

Due to the metabolic nature of osteoporosis, this study was conducted to identify metabolomic studies investigating the metabolic profile of low bone mineral density (BMD) and osteoporosis. A comprehensive systematic literature search was conducted through PubMed, Web of Science, Scopus, and Embase databases up to April 08, 2020, to identify observational studies with cross-sectional or case-control designs investigating the metabolic profile of low BMD in adults using biofluid specimen via metabolomic platform. The quality assessment panel specified for the “omics”-based diagnostic research (QUADOMICS) tool was used to estimate the methodologic quality of the included studies. Ten untargeted and one targeted approach metabolomic studies investigating biomarkers in different biofluids through mass spectrometry or nuclear magnetic resonance platforms were included in the systematic review. Some metabolite panels, rather than individual metabolites, showed promising results in differentiating low BMD from normal. Candidate metabolites were of different categories including amino acids, followed by lipids and carbohydrates. Besides, certain pathways were suggested by some of the studies to be involved. This systematic review suggested that metabolic profiling could improve the diagnosis of low BMD. Despite valuable findings attained from each of these studies, there was great heterogeneity regarding the ethnicity and age of participants, samples, and the metabolomic platform. Further longitudinal studies are needed to validate the results and confirm the predictive role of metabolic profile on low BMD and fracture. It is also mandatory to address and minimize the heterogeneity in future studies by using reliable quantitative methods. Summary: Due to the metabolic nature of osteoporosis, researchers have considered metabolomic studies recently. This systematic review showed that metabolic profiling including different categories of metabolites could improve the diagnosis of low BMD. However, great heterogeneity was observed and it is mandatory to address and minimize the heterogeneity in future studies.

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Fig. 1

Data availability

All data are available upon request.

Abbreviations

ANCOVA:

Analysis of covariance

AUC:

Area under the curve

BMD:

Bone mineral density

CE-TOFMS:

Capillary electrophoresis time of flight mass spectrometer

DXA:

Dual-energy X-ray absorptiometry

ESI-TOFMS:

Electrospray ionization-time of flight mass spectrometer

GC-MS:

Gas chromatography-mass spectrometry

HDL:

High-density lipoprotein

HILIC LC-MS:

Hydrophilic interaction liquid chromatography-mass spectrometry

HMDB:

Human Metabolite Database

HNMR:

Proton nuclear magnetic resonance

LC-MS:

Liquid chromatography-mass spectrometry

LC-MS/MS:

Liquid chromatography-tandem mass spectrometry

LDL:

Low-density lipoprotein

MS:

Mass spectrum

OPLS-DA:

Orthogonal projections to latent structures discriminant analysis

PCA:

Principal component analysis

PLS-DA:

Partial least squares discriminant analysis

PRISMA:

Preferred Reporting Items for Systematic Review and Meta-analysis

QUADAS:

Quality assessment of studies of diagnostic accuracy included in systematic reviews

QUADOMICS:

An adaptation of QUADAS specified for “-omics”-based diagnostic research

RP LC-MS:

Reverse-phase liquid chromatography-mass spectrometry

SMDCCA:

Sparse multiple discriminative canonical correlation analysis, multivariate method for cross-data association

UHPLC/tandem MS:

Ultra-high-performance liquid chromatography/tandem mass spectrometry

UPLC-MS:

Ultra-performance liquid chromatography-mass spectrometry

UPLC/TQMS:

Ultra-performance liquid chromatography coupled with tandem quadrupole mass spectrometry

VLDL:

Very low-density lipoprotein

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Panahi, N., Arjmand, B., Ostovar, A. et al. Metabolomic biomarkers of low BMD: a systematic review. Osteoporos Int (2021). https://doi.org/10.1007/s00198-021-06037-8

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Keywords

  • Biomarkers
  • Bone mineral density
  • Metabolomics
  • Osteoporosis
  • Systematic review