Metabolite profiling of osteoporosis and atherosclerosis


A study in the journal Vascular Health and Risk Management has found significant differences in the metabolite profiling of altered amino acid and lipoprotein metabolism in participants with atherosclerosis and osteoporosis, compared with those in healthy menopausal women.

“Atherosclerosis and osteoporosis are common causes of morbidity and mortality in postmenopausal women and are connected via an unknown mechanistic link,” wrote the Finnish authors. Metabolite profiling of blood samples may allow the identification of new biomarkers and pathways for this enigmatic association.”

The cross-sectional study studied the difference in 148 metabolite levels from serum samples among 280 postmenopausal women with atherosclerosis and osteoporosis and those without, representing a randomly selected sample from the population-based Kuopio Osteoporosis Risk Factor and Prevention (OSTPRE) study.

The mean age of the study population was 73.6, whereas 23.6% of women were obese (BMI >30 kg/m2) and 3.6% of women were current smokers.

A subset of 134 women were divided into four groups: osteoporosis with carotid artery calcifications (CAC) (n = 16, group I); non-osteoporosis with no CAC (n = 59, group II); high carotid artery intima-media thickness (cIMT) tertile with osteoporosis (n = 11, group III); and low cIMT tertile without OP (n = 48, group IV).

The fat mass and body mass index (BMI) were significantly lower in groups I and III compared to those in groups II and IV.

Significant differences existed in several metabolite levels between groups I and II. For instance, the acetate level was lower in group I than in group II: mean ± standard deviation (SD) 0.033 vs. 0.041, respectively; 95% confidence interval (CI): 0.018 to 0.15 (P = 0.014).

Results were similar for diacylglycerol (P = 0.002), leucine (P = 0.031), valine (P = 0.022) and several very low-density lipoprotein (VLDL) metabolite levels, which were significantly lower in group I than in group II.

“In our study, associations were found with the CAC groups only but not with the high cIMT group,” wrote the authors. “This suggests that VLDL may reflect the link between bone loss and vascular calcifications. Lipid metabolism may be accelerated in subjects with CAC and osteoporosis compared with that in the healthy group, which could explain the low VLDL particle levels.”

However, no associations were found in adjusted analyses of total body fat mass, age and statin use (P > 0.05). Adjustments with the use of statins weakened the connection in the study, according to the authors, “which may be due to the effects of statins on lipoprotein metabolism,” they said.

Wide metabolomic analyses could provide a fresh insight for clinical practice to estimate the risk of possible cross-linking endpoints, such as stroke or fracture in a population having osteoporosis or atherosclerosis. “In other words, change in certain metabolite levels may be a risk predictor for atherosclerosis in patients having osteoporosis,” the authors wrote.

Because the causative mechanisms remain unknown, the authors advocate further studies. Follow-up studies also are needed with larger samples to verify the results and identify risk predictors.



Varri M, Niskanen L, Tuomainen T-P, et al.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

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