A Distinctive Human Metabolomics Alteration Associated with Osteopenic and Osteoporotic Patients

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.

Integrating untargeted and targeted metabolomics coupled with pathway analysis reveals muscle disorder in osteoporosis on orchiectomized mice

“…Strong logical and biochemical interaction seasonalized the occurrence of these three elements. The pathway analysis in Figure S7 echoes with the conclusion of inflammation by disorders including phenylalanine metabolism, histidine metabolism, purine metabolism, which are closely related to inflammation 44,45,51 . At the same time, the reduction of carnosine and anserine level provide absent of anti-oxidative process, where oxidative stress is aggravated and the risk of necrosis was hastened.…”

“…Main pathway disorders included phenylalanine metabolism, histidine metabolism, purine metabolism. It had been reported that these pathways are related with OP not only in bone tissue but also in blood 44,45 . Our study has provided the analyses by combining untargeted and targeted metabolomics to prove the disturbance of muscle metabolism by OP disease in early stage, where severe and obvious muscle dysfunction have not occurred.…”

Applications of Metabolomics in Calcium Metabolism Disorders in Humans

“…The most frequently dysregulated metabolic pathways in low bone mineral density included histidine metabolism, glyoxylate, aminoacyl-tRNA biosynthesis, dicarboxylate metabolism and unsaturated fatty acid biosynthesis. Additional analyses revealed differences between patients with osteopenia and osteoporosis, including different levels of carboxy-4-methyl-5-propyl-2-2furanopropionic acid, carnitine derivatives, phosphatidylcholine, sphingomyelin and palmitic acid [ 32 ].…”

GCTOF-MS Combined LC-QTRAP-MS/MS Reveals Metabolic Difference Between Osteoarthritis and Osteoporotic Osteoarthritis and the Intervention Effect of Erxian Decoction

“…The reason why recent studies have focused on the role of metabolic abnormalities in Osteoporotic OA is precisely due to the similarities in the loss of bone homeostasis between OP and OA (8). Studies have shown that under high body mass index, excessive adipokines release and metabolic changes lead to the occurrence of OP and increased fracture risk (9)(10)(11). It is well known that a high body mass index not only brings more mechanical load to OA by increasing body weight but also increases the risk of OA by inducing sterile inflammation through adipokines (12).…”