Unique plasma metabolomic signature of osteonecrosis of the femoral head

Abstract

Metabolomic analysis was performed to determine the metabolomic signature of osteonecrosis of the femoral head (ONFH), and to investigate the underlying relationship between the metabolomic signature and the pathogenesis of ONFH. Plasma samples were collected from 30 ONFH patients and 30 normal subjects. The global metabolomic profile was obtained through a combination of high-throughput liquid-and gas-chromatography-based mass spectrometry analyses. All statistical analyses were conducted using the R software. The results showed clear differences in the metabolomic signature between the plasma of ONFH patients compared with normal subjects. Among the 354 identified metabolites, the expression of 123 metabolites were significantly changed in ONFH patients compared with normal subjects (p < 0.05, q < 0.10). Bioinformatics analysis revealed that these abnormal metabolites were mainly involved in lipid-, glutathione-, nucleotide-, and energy-associated pathways, which might be related to enhanced inflammation, oxidative stress, and energy deficiency due to ONFH. This study provides the first metabolomic analysis of ONFH, and identifies a previously unrecognized metabolic signature in ONFH plasma. The results offer new insights into the pathological mechanisms of ONFH through its influence on metabolic pathways, providing the requisite framework for identifying biomarkers or novel targets for therapeutic intervention. ß

Systems analysis of avascular necrosis of femoral head using integrative data analysis and literature mining delineates pathways associated with disease

“…Metabolites belonging to polyamine and urea pathway was also found to be deregulated 1 . Metabolomics of plasma of AVNFH showed 48 differentially regulated metabolites 23 while that of bone trabeculae showed 53 differentially regulated metabolites 25 . Pathway annotation analysis of these metabolites belonging to individual cohorts were carried out using MetaboAnalyst 30 .…”

“…Data from three published metabolomic analyses were used for our study. Our previous study involving targeted metabolomics of plasma samples from 14 patients compared to 14 healthy control samples were used 1 www.nature.com/scientificreports/ patients compared to 30 healthy controls 23 , and a bone trabecular metabolomics study of 28 patients compared to 20 controls 25 .…”

Serum Biomarkers Related to Glucocorticoid‐Induced Osteonecrosis of the Femoral Head: A Prospective Nested Case‐Control Study

“…Bian et al reported that dexamethasone regulated lipid metabolism‐associated microRNAs in osteogenically induced human mesenchymal stem cells. Metabolomics analysis performed on 30 patients with GC‐induced ONFH and 30 healthy controls revealed that the abnormal metabolites induced by GCs were primarily in lipid‐, glutathione‐, nucleotide‐, and energy‐associated pathways …”

“…Metabolomics analysis performed on 30 patients with GC-induced ONFH and 30 healthy controls revealed that the abnormal metabolites induced by GCs were primarily in lipid-, glutathione-, nucleotide-, and energy-associated pathways. 19 HDL and its major functional component apo-A1 counteract excessive cellular cholesterol accumulation and promote reverse cholesterol transport. In the present study, patients with lower baseline levels of HDL-C tended to have a higher risk of GC-induced ONFH (Fig.…”

Attenuated serum adiponectin levels are associated with disease severity in patients with non-traumatic osteonecrosis of the femoral head

“…In recent years, authors looking to embrace a consensus of opinion related to the pathogenesis of ONFH in their works have been devoting increasingly more attention to the importance of abnormal lipid metabolism 21. Research works over these years have supported the fact that ONFH is a problem of not merely local avascular status associated with bone necrosis but also including a systemic angle – in view of a significant contribution of hyperlipidemia 22.…”