Abstract
Osteoporosis is becoming a highly prevalent disease in a large proportion of the global aged population. Serum metabolite markers may be important for the treatment and early prevention of osteoporosis. Serum samples from 32 osteoporosis and 32 controls were analyzed by untargeted metabolomics and lipidomic approaches performed on an ultra-high performance liquid chromatography and high-resolution mass spectrometry (UHPLC-HRMS) system. To find systemic disturbance of osteoporosis, weighted gene correlation network analysis (WGCNA) and statistical methods were employed for data-mining. Then, an in-depth targeted method was utilized to determine potential markers from the family of key metabolites. As a result, 1,241 metabolites were identified from untargeted methods and WGCNA indicated that lipids metabolism is deregulated and glycerol phospholipids, sphingolipids, fatty acids, and bile acids (BA) are majorly affected. As key metabolites of lipids metabolism, 66 bile acids were scanned and 49 compounds were quantified by a targeted method. Interestingly, hyocholic acids (HCA) were found to play essential roles during the occurrence of osteoporosis and may be potential markers. These metabolites may be new therapeutic or diagnosis targets for the screening or treatment of osteoporosis. Quantified measurement of potential markers also enables the establishment of diagnostic models for the following translational research in the clinic.
Highlights
Osteoporosis is a progressive systemic bone disease that is characterized by bone loss and microstructural deterioration and results in increased bone fragility, which affects over 200 million people worldwide (Curtis et al, 2017; Compston et al, 2019)
The results revealed that bile acid metabolism was converted from the classical pathway to the alternative pathway (CA: chenodeoxycholic acid (CDCA))
There was a change in the progression of taurine conjugation of secondary bile acids (BA) in the liver (taurolithocholic acid (TLCA): LCA). These results indicated that gut microbiota and related BA metabolism may act as an important role in the occurrent osteoporosis (Figure 5)
Summary
Osteoporosis is a progressive systemic bone disease that is characterized by bone loss and microstructural deterioration and results in increased bone fragility, which affects over 200 million people worldwide (Curtis et al, 2017; Compston et al, 2019). Complications of osteoporosis such as chronic pain, fracture and disability seriously affect the quality of life of elderly individuals. Fracture is the most serious complication, with more than 8.9 million osteoporosis-related fractures occurring annually (Cruz-Jentoft and Sayer, 2019). Due to the absence of obvious symptoms and sensitive biomarkers, many patients
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