Objective To explore the correlation between lipid metabolism disorder in bone marrow and primary osteoporosis(OP),and to evaluate the regulation and clinical significance of lipid metabolism-related genes in primary OP.Methods The differentially expressed genes(DEGs)of OP were obtained from GSE35959 dataset,and combined with human lipid metabolism-related genes to screen the differentially expressed lipid metabolism genes of OP patients.The STRING 11.0 database was used to establish a protein-protein interaction(PPI)network,and the receive operation characteristic curve was used to explore the significance of key proteins in PPI in the differential diagnosis of OP.Results A total of 2105 DEGs(1940 up-regulated genes and 165 down-regulated genes)were identified in the mesenchymal stem cells of OP patients.Of them,75 DEGs were related to lipid metabolism and mainly involved in the cellular lipid metabolism and small molecule lipid metabolism through arachidonic acid and glycerophospholipid metabolism related signaling pathways.The PPI of lipid metabolism-related genes in OP patients contained 75 nodes and 65 interaction relationships(P<0.01).There were 7 nodes(HELZ2,CYP4A11,ALOX5,PTGS2,CYP4F2,ALOX12B,FABP4)with an interaction relationship≥5.The expression levels of these genes in OP patients were significantly higher than those in the control group(P<0.05).ALOX5 expression was negatively correlated with HELZ2 expression(P<0.05).HELZ2,CYP4A11,ALOX5,PTGS2,CYP4F2,ALOX12B and FABP4 all showed differential diagnosis significance for OP,and the area under the AUC curve was all>0.80(P<0.05).Conclusion Primary OP patients have lipid metabolism disorders in bone marrow,and lipid metabolism-related genes have a certain regulatory effect on the above process.Seven lipid metabolism-related genes screened in this study have certain differential diagnosis ability for primary OP.