Perturbations of lipids and oxidized phospholipids in lipoproteins of patients with postmenopausal osteoporosis evaluated by asymmetrical flow field-flow fractionation and nanoflow UHPLC–ESI–MS/MS

Osteoporosis, a degenerative bone disease characterized by reduced bone mass and high risk of fragility, is associated with the alteration of circulating lipids, especially oxidized phospholipids (Ox-PLs). This study evaluated the lipidomic changes in lipoproteins of patients with postmenopausal osteoporosis (PMOp) vs. postmenopausal healthy controls. High-density lipoproteins (HDL) and low-density lipoproteins (LDL) from plasma samples were size-sorted by asymmetrical flow field-flow fractionation (AF4). Lipids from each lipoprotein were analyzed by nanoflow ultrahigh performance liquid chromatography–electrospray ionization–tandem mass spectrometry (nUHPLC–ESI–MS/MS). A significant difference was observed in a subset of lipids, most of which were increased in patients with PMOp, when compared to control. Phosphatidylethanolamine plasmalogen, which plays an antioxidative role, was increased in both lipoproteins (P-16:0/20:4, P-18:0/20:4, and P-18:1/20:4) lysophosphatidic acid 16:0, and six phosphatidylcholines were largely increased in HDL, but triacylglycerols (50:4 and 54:6) and overall ceramide levels were significantly increased only in LDL of patients with PMOp. Further investigation of 33 Ox-PLs showed significant lipid oxidation in PLs with highly unsaturated acyl chains, which were decreased in LDL of patients with PMOp. The present study demonstrated that AF4 with nUHPLC–ESI–MS/MS can be utilized to systematically profile Ox-PLs in the LDL of patients with PMOp.