Abstract
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.
Highlights
Osteoporosis, a chronic degenerative disease, is characterized by reduced bone mass, which leads to an increased risk of bone fracture [1,2,3]
12 oxidized phospholipids (Ox-PLs) species were found to be significantly (>1.5-fold with p < 0.05) increased in patients with postmenopausal osteoporosis (PMOp) compared to controls and originated from the six abovementioned relatively abundant PL species
18:0/18:2, all of which displayed a relatively abundant original intact species. These results indicate that significant lipid oxidation occurred in PLs with highly unsaturated acyl chains, which were decreased in the low-density lipoproteins (LDL) of patients with PMOp when compared to controls
Summary
Osteoporosis, a chronic degenerative disease, is characterized by reduced bone mass, which leads to an increased risk of bone fracture [1,2,3]. Osteoporosis is recognized as a major public health problem worldwide, as it limits patient mobility to a greater degree than strokes and myocardial infarction [2]. Over their lifetime, about 30% of women and 12% of men are expected to develop osteoporosis [3]. Estrogen deficiency is a major risk factor in menopausal women, since the decrease in estrogen levels perturbs the activity of bone remodeling, eventually leading to low bone density [4,5]. Bone loss is associated with increased bone resorption of osteoclasts and decreased bone
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