Metabolomic biomarkers of low BMD: a systematic review

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.