<p>Metabolite Profiling of Osteoporosis and Atherosclerosis in Postmenopausal Women: A Cross-Sectional Study</p>

Abstract

Purpose: Atherosclerosis (AS) and osteoporosis (OP) are common causes of morbidity and mortality in postmenopausal women and are connected via an unknown mechanistic link. Metabolite profiling of blood samples may allow the identification of new biomarkers and pathways for this enigmatic association. Patients and Methods: We studied the difference in 148 metabolite levels from serum samples in postmenopausal women with AS and OP compared with those in healthy participants in this cross-sectional study. Quantitative AS was assessed by carotid artery intima-media thickness (cIMT) and carotid artery calcifications (CACs) by ultrasound, as well as OP by femoral neck (FN) bone mineral density (BMD) and 148 metabolic measures with high-throughput proton (1 H) nuclear magnetic resonance (NMR) in serum samples from 280 postmenopausal (PM) women. Subjects were a randomly selected subsample from the population-based Kuopio Osteoporosis Risk Factor and Prevention (OSTPRE) study. The final study population included the following groups: OP with CAC (n=16, group I), non-OP with no CAC (n=59, group II), high cIMT tertile with OP (n=11, group III) and low cIMT tertile without OP (n=48, group IV). Results: There were differences in several metabolite levels between groups I and II. The acetate level was lower in group I compared to that in group II (group I mean ± SD: 0.033 ± 0.0070; group II: 0.041 ± 0.014, CI95%: 0.018-0.15, p=0.014). The result was similar with diacylglycerol (p=0.002), leucine (p=0.031), valine (p=0.022) and several very low-density lipoprotein (VLDL) metabolite levels, which were lower in group I compared to those in group II. However, no associations were found in adjusted analyses with total body (TB) fat mass (FM), age and statin use (p>0.05). Conclusion: Our novel study found differences in the metabolite profiling of altered amino acid and lipoprotein metabolism in participants with OP and AS compared with those in healthy women. The causative mechanisms remain unknown and further studies are needed.

Evaluating the association between amino acid and acylcarnitine profiles and different levels of coronary artery disease risk in postmenopausal women using targeted metabolomics technique

“…After acute myocardial infarction, the lower circulating lysine provides other evidence supporting our results 28,29 . The assessment of serum levels of metabolites from postmenopausal women with atherosclerosis and osteoporosis compared with healthy participants showed apparent differences in amino acid profile 13 …”

“…There is no sharing of metabolite profile between us and Värri et al's 13 study, possibly related to the alteration of metabolites in postmenopausal osteoporosis and the simultaneous occurrence with atherosclerosis In Floegel's 44 study, none of the metabolites, such as acylcarnitines and amino acids, were associated with the risk of myocardial infarction in healthy adults.…”

“…28,29 The assessment of serum levels of metabolites from postmenopausal women with atherosclerosis and osteoporosis compared with healthy participants showed apparent differences in amino acid profile. 13 Although the exact reason for our finding cannot be ascertained according to the present study, several possibilities derived from the available literature should be considered.…”

“…42 For instance, in ischemic disease, decreased blood perfusion leads to reduced rates of fatty acids β-oxidation, 12 which is associated with the intensity and deterioration of ischemia. 43 There is no sharing of metabolite profile between us and Värri et al's 13 study, possibly related to the alteration of metabolites in postmenopausal osteoporosis and the simultaneous occurrence with atherosclerosis In Floegel's 44 study, none of the metabolites, such as acylcarnitines and amino acids, were associated with the risk of myocardial infarction in healthy adults.…”

Metabolic profiling links cardiovascular risk and vascular end organ damage

“…Previous studies showed lower acetate concentrations in postmenopausal women with carotid artery calcification [47] and in myocardial ischemia patients without stenosis [48] compared to controls.…”