The Plasma Metabolomics Study Of Early Nontraumatic Femoral Head Necrosis

BackgroundAs a potential disabling disease,the incidence of osteonecrosis of the femoral head was significantly increasing in recent years,the world has about 2000,ten thousand patients,about 300,000 to 600,000 Americans suffer from femoral head necrosis,and about 20,000 new cases each year need to clinical treatment,including about 5 million people in China.In China,in recent years,the incidence of the disease is also on the rise with the increase of hormone abuse and alcoholism.In addition,the disease occurs in the middle and middle of life,so it brings great economic burden to the society and the family.Clinical findings show that most of the typical osteonecrosis of the femoral head(ONFH)have obvious imaging changes and enter into the irreversible middle and late stage,when the optimal treatment opportunity is often lost.Therefore,how to detect lesions early to avoid necrosis progression has become the focus of current research.At present,the clinical diagnosis of femoral head necrosis mainly depends on symptoms,signs,X-ray and MRI.Although MRI can provide certain help for early diagnosis,it is difficult to be used for screening because of its high interference and price.Metabolomics,as a new technique emerging in recent years,is helpful to understand the metabolic changes of diseases and to find small molecular markers of diseases,thus providing a new possibility for the early diagnosis of femoral head necrosis.Metabolomics has been successfullyapplied to the study of common orthopedic diseases such as osteoarthritis,ankylosing spondylitis and bone tumors,and revealed the metabolic pathways of many orthopedic diseases.However,studies on plasma metabolomics of femoral head necrosis are rare.In this study,the metabolic characteristics of non-traumatic femoral head necrosis were studied retrospectively by UPLC-MS/MS.ObjectiveThis study was based on the metabolomics research platform of UPLC-MS/MS,and the plasma samples of ONFH patients and healthy people were analyzed by metabolomics.By extracting and analyzing their metabolites,the differential metabolites were screened out and analyzed.This will provide new ideas for the early diagnosis and preventive treatment of femoral osteonecrosis.MethodsBlood samples from 28 patients with femoral head necrosis were collected as the experimental group and 30 normal people as the control group.The plasma sample metabolites were extracted and detected by UPLC-MS/MS spectrometry tandem analyzer.After pretreatment of the detection results,PCA(principal component analysis),PLS-DA(least partial squares discriminant analysis)and OPLS-DA(orthogonal partial least squares discriminant analysis)models were established.According to the multivariate and unit statistical analysis,the difference variables were screened out.Then we imported the obtained variables into the machine’s own software Shortcut to PeakView.We exported the second level mass spectra and compared them in Massbank and HMDB database to find the possible corresponding substances.Through MetPA analysis,metabolic pathways with influence factors greater than 0.1 were screened out,that is,pathways with obvious changes.The substances with obvious changes were first combined with logistic binary regression,and then subject work(ROC)curve was analyzed to evaluate its diagnostic value.ResultsPlasma specimens from patients with femoral head necrosis showed significant changes compared with healthy plasma.The expression patterns of blood samples and healthy blood metabolites in patients with femoral head necrosis can be clearly distinguished in PCA,PLS-DA and OPLS-DA models.Finally,18 different metabolites were screened out and their corresponding substances were deduced according to the second-order mass spectrometry.Among them,Octanoyl-LCarnitine、PC(16:0/0:0)and 3b,16a-Dihydroxyandrostenone sulfate can be used as candidate diagnostic markers for femoral head necrosis.Pathway analysis showed that phospholipid biosynthesis,acyl-coa oxidation of long-chain fatty acids,and oxidation of short-chain fatty acids,linoleic acid metabolism were closely related to non-traumatic femoral head necrosis.ConclusionIn this study,blood tissue metabolites were successfully extracted and differentiated metabolites in plasma were determined,which laid a foundation for further research on the specific metabolic mechanism of blood metabolic markers for non-traumatic femoral head necrosis.However,due to the small sample size,it is necessary to expand the sample size.