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. 2025 Jan 21;37(1):28.
doi: 10.1007/s40520-024-02923-3.

Combining untargeted and targeted metabolomic profiling reveals principal differences between osteopenia, Osteoporosis and healthy controls

Bing Tan  1 , Yan Cheng  1 , Junfeng Li  1 , Yuhao Zheng  1 , Cong Xiao  1 , Haoning Guo  1 , Bing Wang  1 , Jianyuan Ouyang  1 , Wenmin Wang  2 , Jisheng Wang  3
Affiliations

Combining untargeted and targeted metabolomic profiling reveals principal differences between osteopenia, Osteoporosis and healthy controls

Bing Tan et al. Aging Clin Exp Res. .

Abstract

Background: Osteopenia (ON) and osteoporosis (OP) are highly prevalent among postmenopausal women and poses a challenge for early diagnosis. Therefore, identifying reliable biomarkers for early prediction using metabolomics is critically important.

Methods: Initially, non-targeted metabolomics was employed to identify differential metabolites in plasma samples from cohort 1, which included healthy controls (HC, n = 23), osteonecrosis (ON, n = 36), and osteoporosis (OP, n = 37). Subsequently, we performed targeted metabolomic validation of 37 amino acids and their derivatives in plasma samples from cohort 2, consisting of healthy controls (HC, n = 10), osteonecrosis (ON, n = 10), and osteoporosis (OP, n = 10).

Results: The non-targeted metabolomic analysis revealed an increase in differential metabolites with the progression of the disease, showing abnormalities in lipid and organic acid metabolism in ON and OP patients. Several substances were found to correlate positively or negatively with bone mineral density (BMD), for example, N-undecanoylglycine, sphingomyelins, and phosphatidylinositols exhibited positive correlations with BMD, while acetic acid, phenylalanine, taurine, inosine, and pyruvic acid showed negative correlations with BMD. Subsequently, targeted validation of 37 amino acids and their metabolites revealed six amino acids related to ON and OP.

Conclusion: Significant metabolomic features were identified between HC and patients with ON/OP, with multiple metabolites correlating positively or negatively with BMD. Integrating both targeted and non-targeted metabolomic results suggests that lipid, organic acid, and amino acid metabolism may represent important metabolomic characteristics of patients with OP, offering new insights into the development of metabolomic applications in OP.

Keywords: Biomarker; Metabolomics; Osteopenia; Osteoporosis; Postmenopausal women.

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Conflict of interest statement

Declarations. Informed consent: was obtained from all subjects involved in the study.Written informed consent has been obtained from the patient(s) to publish this paper. Institutional review board statement: The study was conducted in accordance with the Declaration of Helsinki, and approved by the Institutional Ethics Committee of The Third Hospital of Mian Yang (2024,Reviewed, No.3 and February 26, 2024). Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Overview of the study design. The illustration was created with BioRender
Fig. 2
Fig. 2
Partial least squares discriminant analysis and statistical analysis of differential metabolites. (A) PLS-DA of the metabolomics data from HC, ON, and OP groups, (B) Permutation tests of PLS-DA models, (C) Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathways enriched by significantly differential metabolites in ON versus HC, in OP versus HC, and in OP versus ON, (D) Volcano plots of the significantly differential metabolites in ON versus HC, (E) in OP versus HC, and (F) in OP versus ON
Fig. 3
Fig. 3
Clustering of metabolic trajectories using differential metabolites among HC, ON, and OP. (A) Cluster 1, (B) Cluster 2, (C) Cluster 3, (D) Cluster 4
Fig. 4
Fig. 4
Differential amino acid levels in targeted metabolomics results. Asp, L-Aspartic acid; Asn, L-Asparagine; Lys, L-Lysine; Thr, L-Threonine; Cit, L-Citrulline; EtN, Ethanolamine
Fig. 5
Fig. 5
ROC curves for the six amino acids selected in the targeted analysis. Asp, L-Aspartic acid; Asn, L-Asparagine; Lys, L-Lysine; Thr, L-Threonine; Cit, L-Citrulline; EtN, Ethanolamine
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