Association between the metabolome and bone mineral density in pre- and post-menopausal Chinese women using GC-MS

Abstract

The present study describes for the first time, a metabolic profile reflecting the osteoporosis progression in 364 pre- and postmenopausal Chinese women using GC-MS. In order to accurately evaluate the dynamic changes of metabolites along with estrogen deficiency and osteoporosis progression, we divided these subjects into the following four groups: premenopausal women with normal bone mass density (BMD, group I), postmenopausal women with normal BMD (group II), postmenopausal women with osteopenia (group III) and postmenopausal women with osteoporosis (group IV), according to their menopause or low BMD status. Principal component analysis (PCA) and Partial least squares-discriminant analysis (PLS-DA) were used to evaluate the associations of metabolic changes with low BMD or estrogen deficiency. Twelve metabolites identified by the PLS-DA model were found to be able to differentiate low BMD groups from normal BMD groups. Of the 12 metabolites, five free fatty acids (LA, oleic acid, AA and 11,14-eicosadienoic acid) have the most potential to be used as osteoporosis biomarkers due to their better correlations with BMD, and high sensitivity and specificity in distinguishing the low BMD groups from the normal BMD groups calculated by the receiver operating characteristic curve (ROC). The lipid profile may be useful for osteoporosis prediction and diagnosis.

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

“…Although the total TG amounts were not changed in HDL in our study, they were significantly increased in the LDL fraction due to contributions from two highly unsaturated TG species (50:4 and 54:6). While the relationship between the increase of TG and the development of PMOp is not clearly understood, similarly to our study, the overall TG level has been reported to increase in postmenopausal women [35]. Moreover, TG species with more unsaturated acyl chains appear to be more influenced than those with saturated chains.…”

Metabolomics and Its Application in the Development of Discovering Biomarkers for Osteoporosis Research

“…Through the comparison of metabolic differences among different groups, researchers are able to identify specific and sensitive metabolites that would be used in the diagnosis and prognosis of osteoporosis. A study from Qi et al involved 364 female subjects divided into four groups (premenopausal women with normal BMD, postmenopausal women with normal BMD, postmenopausal women with osteopenia and postmenopausal women with osteoporosis), from Jiangsu Province geriatric hospital, China [22]. They studied the connection between osteoporosis progression and BMD in postmenopausal women and discovered biomarkers that could distinguish low BMD from normal BMD.…”

“…Patients with lower BMD and osteoporosis also have higher lipid levels. Qi et al found that postmenopausal women with osteopenia and osteoporosis had lower concentration of high-density lipoprotein cholesterol (HDL-C) and higher concentrations of low-density lipoprotein cholesterol (LDL-C), triglycerides and total cholesterol [22]. The result from Xue et al showed that ovariectomy induced an increase of plasma levels of low-density lipoprotein (LDL), choline, glycerophosphatide and lipid in mice, which indicated that the biological mechanism of osteoporosis is associated with lipid metabolism [51].…”

“…Most metabolomics data describing menopausal or osteoporosis metabolites alterations have been generated from cross-sectional studies, which are easier to conduct, but do not allow the investigation about the metabolites alterations along with osteoporosis progression [22,30]. The measurement of bone mass with the chronological alteration trend of biomarkers may reliably identify the women at perimenopause who are at highest risk of developing osteoporosis later in life.…”

“…The speed, sensitivity and robustness of metabolomics technique are proven to be somewhat better than the traditional immunoassays or chemical-reaction detections. The fold changes of metabolites in the biological fluids were more significant than those bone turnover markers [22]. …”