Metabolomics of Osteoporosis in Humans: A Systematic Review

To systematically review recent studies investigating the association between metabolites and bone mineral density (BMD) in humans.

Using predefined keywords, we searched literature published from Jan 1, 2019 to Feb 20, 2022 in PubMed, Web of Science, Embase, and Scopus. Studies that met the predefined exclusion criteria were excluded. Among the included studies, we identified metabolites that were reported to be associated with BMD by at least three independent studies.

A total of 170 studies were retrieved from the databases. After excluding studies that did not meet our predefined inclusion criteria, 16 articles were used in this review. More than 400 unique metabolites in blood were shown to be significantly associated with BMD. Of these, three metabolites were reported by ≥ 3 studies, namely valine, leucine and glycine. Glycine was consistently shown to be inversely associated with BMD, while valine was consistently observed to be positively associated with BMD. Inconsistent associations with BMD was observed for leucine. With advances in metabolomics technology, an increasing number of metabolites associated with BMD have been identified. Two of these metabolites, namely valine and glycine, were consistently associated with BMD, highlighting their potential for clinical application in osteoporosis. International collaboration with a larger population to conduct clinical studies on these metabolites is warranted. On the other hand, given that metabolomics could be affected by genetics and environmental factors, whether the inconsistent association of the metabolites with BMD is due to the interaction between metabolites and genes and/or lifestyle warrants further study.