Metabolite Profiling of Osteoporosis and Atherosclerosis in Postmenopausal Women: A Cross-Sectional Study

Vasc Health Risk Manag. 2020 Dec 2:16:515-524. doi: 10.2147/VHRM.S279028. eCollection 2020.

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 (1H) 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.

Keywords: acetate; carotid artery calcification; carotid intima-media thickness; metabolomics; osteoporosis; postmenopausal women.

MeSH terms

  • Aged
  • Amino Acids / blood*
  • Atherosclerosis / blood*
  • Atherosclerosis / diagnostic imaging
  • Biomarkers / blood
  • Case-Control Studies
  • Cross-Sectional Studies
  • Energy Metabolism*
  • Female
  • Humans
  • Lipids / blood*
  • Magnetic Resonance Spectroscopy
  • Metabolomics*
  • Osteoporosis, Postmenopausal / blood*
  • Osteoporosis, Postmenopausal / diagnostic imaging
  • Postmenopause / blood*

Substances

  • Amino Acids
  • Biomarkers
  • Lipids

Grants and funding

Academy of Finland (Kröger H, grant number 250707), Kuopio University Hospital EVO-grants (Tuppurainen M, grant number 5302460), Kuopio University Hospital Funding (V.T.R. grant number 5203024), the Ministry of Education and Culture of Finland (grant numbers 116/626/2012, 46/627/2011 and 93/627/2010), and Strategic Funding of the University of Eastern Finland (grant number 931053) provided funding for this study. The foregoing grants were appropriated for the original OSTPRE study for 20- and 25-year follow-up measurements and analyses. Finnish Medical Society Duodecim grant of a young researcher (Eka Grant, 2016), abetment grant (grant number 2038) and Finnish Menopause Society personal grant (2018) were appropriated as personal grants for MV for his PhD thesis.