Association of Plasma Lipids and Polar Metabolites with Low Bone Mineral Density in Singaporean-Chinese Menopausal Women: A Pilot Study

Abstract

The diagnosis of osteoporosis is mainly based on clinical examination and bone mineral density assessments. The present pilot study compares the plasma lipid and polar metabolite profiles in blood plasma of 95 Singaporean-Chinese (SC) menopausal women with normal and low bone mineral density (BMD) using an untargeted metabolomic approach. The primary finding of this study was the association between lipids and femoral neck BMD in SC menopausal women. Twelve lipids were identified to be associated with low BMD by the orthogonal partial least squares (OPLS) model. Plasma concentrations of eight glycerophospholipid, glycerolipid, and sphingolipid species were significantly lower in menopausal women with low BMD but higher in two glycerophospholipid species (phosphatidylinositol and phosphatidic acid). Further, this study found no significant differences in plasma amino acid metabolites. However, trends for lower 4-aminobutyric acid, turanose, proline, aminopropionitrile, threonine, and methionine were found in women with low BMD. This pilot study identified associations between lipid metabolism and femoral neck BMD in SC women. Further studies are required on larger populations for evaluating the bone health effect of these compounds and their usefulness as clinical biomarkers for osteoporosis prediction in women.

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

“…Of particular interest is PEp, which is known to play an antioxidative role against lipid oxidation. Similar to an earlier study showing an increase of PE (P-18:0/20:4) in menopausal women with low BMD [12], our study showed significant increases in PE (P-16:0/20:4, P-18:0/20:4, and P-18:1/20:4) in both lipoprotein fractions of patients with PMOp. Therefore, the elevation of PEp levels strongly supports the hypothesis that lipid oxidation is increased in patients with PMOp.…”

“…PEp is known to protect the unsaturated acyl chain of lipids against oxidative damage from ROS [30]. The increase in PEp was similarly reported in menopausal women with low bone-mineral density (BMD) compared to the BMD in women with normal bone density in an earlier study [12]. While the last study showed a significant increase of PE P-18:0/20:4 species, the present work showed more detailed information on the accumulated PEp species.…”

“…Since the oxidation of lipoproteins occurs at lipids, bone loss should be associated with alterations in circulating lipid profiles, especially oxidized lipids. Indeed, a correlation between lipid changes and postmenopausal osteoporosis (PMOp) has been found in the femur tissue of osteoporotic mice [10] and human plasma samples [11,12]. Recently, it has been found that inflammatory bioactive lipids, which promote atherosclerosis, also induce bone loss [13], and that oxidized LDL is pathogenically associated with the loss of bone mass [14].…”

Integrative Bone Metabolomics—Lipidomics Strategy for Pathological Mechanism of Postmenopausal Osteoporosis Mouse Model

“…Certain metabolic molecules with important biological functions, including lipids, were omitted from these previous studies. Lipids play an important role in cell function maintenance and energy storage 16 and have a close relationship with osteoporosis 17 – 19 . The traditional metabolomics studies have limitations in the extraction and analysis of lipid molecules, which greatly influenced the characterization of lipids 20 .…”

Innovations in Women’s Bone Health—Appreciating Important “Bone Variables” Besides Estrogen

“…This Issue included work from scientists in five countries and presented an incredible array of perspectives/topics. These bone-relevant variables included shorter leukocyte telomere lengths related to lower BMD in women living with HIV [ 6 ], insulin resistance related to reduced bone strength in menopausal Chinese women without diabetes [ 7 ] and altered polar lipid metabolomics associated with lower femoral neck BMD [ 8 ].…”