A Distinctive Human Metabolomics Alteration Associated with Osteopenic and Osteoporotic Patients

Shereen M Aleidi; Eman A Alnehmi; Mohammed Alshaker; Afshan Masood; Hicham Benabdelkamel; Mysoon M Al-Ansari; Anas M Abdel Rahman

doi:10.3390/metabo11090628

A Distinctive Human Metabolomics Alteration Associated with Osteopenic and Osteoporotic Patients

Metabolites. 2021 Sep 16;11(9):628. doi: 10.3390/metabo11090628.

Authors

Shereen M Aleidi¹, Eman A Alnehmi², Mohammed Alshaker³, Afshan Masood⁴, Hicham Benabdelkamel⁴, Mysoon M Al-Ansari², Anas M Abdel Rahman^{5

6}

Affiliations

¹ Department of Biopharmaceutics and Clinical Pharmacy, School of Pharmacy, The University of Jordan, Amman 11942, Jordan.
² Department of Botany and Microbiology, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.
³ Department of Family Medicine and Polyclinic, King Faisal Specialist Hospital & Research Center, Riyadh 11211, Saudi Arabia.
⁴ Proteomics Resource Unit, College of Medicine, King Saud University, P.O. Box 2925 (98), Riyadh 11461, Saudi Arabia.
⁵ Metabolomics Section, Department of Clinical Genomics, Center for Genomics Medicine, King Faisal Specialist Hospital and Research Centre (KFSHRC), Zahrawi Street, Al Maather, Riyadh 11211, Saudi Arabia.
⁶ Department of Biochemistry and Molecular Medicine, College of Medicine, Al Faisal University, Riyadh 11533, Saudi Arabia.

Abstract

Osteoporosis is a common progressive metabolic bone disease resulting in decreased bone mineral density (BMD) and a subsequent increase in fracture risk. The known bone markers are not sensitive and specific enough to reflect the balance in the bone metabolism. Finding a metabolomics-based biomarker specific for bone desorption or lack of bone formation is crucial for predicting bone health earlier. This study aimed to investigate patients' metabolomic profiles with low BMD (LBMD), including those with osteopenia (ON) and osteoporosis (OP), compared to healthy controls. An untargeted mass spectrometry (MS)-based metabolomics approach was used to analyze serum samples. Results showed a clear separation between patients with LBMD and control (Q² = 0.986, R² = 0.994), reflecting a significant difference in the dynamic of metabolic processes between the study groups. A total of 116 putatively identified metabolites were significantly associated with LBMD. Ninety-four metabolites were dysregulated, with 52 up- and 42 downregulated in patients with LBMD compared to controls. Histidine metabolism, aminoacyl-tRNA biosynthesis, glyoxylate, dicarboxylate metabolism, and biosynthesis of unsaturated fatty acids were the most common metabolic pathways dysregulated in LBMD. Furthermore, 35 metabolites were significantly dysregulated between ON and OP groups, with 11 up- and 24 downregulated in ON compared to OP. Among the upregulated metabolites were 3-carboxy-4-methyl-5-propyl-2-2furanopropionic acid (CMPF) and carnitine derivatives (i.e., 3-hydroxy-11-octadecenoylcarnitine, and l-acetylcarnitine), whereas phosphatidylcholine (PC), sphingomyelin (SM), and palmitic acid (PA) were among the downregulated metabolites in ON compared to OP. This study would add a layer to understanding the possible metabolic alterations associated with ON and OP. Additionally, this identified metabolic panel would help develop a prediction model for bone health and OP progression.

Keywords: bone mineral density (BMD); mass spectrometry; metabolomics; osteopenia; osteoporosis.

Grants and funding

RG-1441-533/Deanship of Scientific Research, King Saud University