A novel lipidome module was found to be significantly associated with surrogate markers of both subclinical osteoporosis and subclinical atherosclerosis, according to the results of the first lipidome-wide system-level association study of its kind, published in Bone.

Previous studies have demonstrated an association between osteoporosis and atherosclerosis, which have common risk factors and pathophysiologic mechanisms. Given that an altered lipidome has been found to be associated with various clinical conditions, the goal of the current study was to perform a lipid co-expression network analysis to identify networks of lipid species jointly associated with markers of both osteoporosis and atherosclerosis.

For this study, the lipidomics data incorporated 437 molecular lipids generated with liquid chromatography-tandem mass spectrometry technique from the serum of 1494 patients aged 30 to 45 years from the 2007 follow-up of the Cardiovascular Risk in Young Finns Study.

The subclinical osteoporotic markers included indices of bone mineral density and content, measured using peripheral quantitative computed tomography from the distal and shaft sites of both the tibia and the radius. The subclinical atherosclerotic markers included carotid and bulbus intima-media thickness measured with high-resolution ultrasound. Networks of lipid species (modules) that were “significantly and jointly correlated with subclinical markers of both osteoporosis and atherosclerosis were considered to be related to the comorbidities,” stated the researchers.


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The researchers identified 12 modules, made up of 6 to 105 highly correlated lipid species, which were assigned a color for downstream analysis.

Of these modules, 3 (turquoise, pink, and yellow) were significantly associated with multiple markers of both osteoporosis and atherosclerosis.

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The turquoise module included 105 lipid species, most of them belonging to the glycerolipid, glycerophospholipid, and sphingolipid classes. It was significantly associated with carotid intima-media thickness variables and with all of the peripheral quantitative computed tomography bone measurements. This module included high-risk cardiovascular ceramides among 20 other ceramides, confirming the known association between ceramides and cardiovascular risk.

Multivariate analysis of lipid species that belonged to the turquoise module identified 37 that were jointly associated with markers of both subclinical osteoporosis and subclinical atherosclerosis. The top 3 of the 37 jointly associated lipid species were all triacylglycerols (TAGs): TAG(18:0/18:0/18:1), TAG(18:0/18:1/18:1), and TAG(16:0/18:0/18:1).

The investigators noted that the study was limited to the subclinical phase of atherosclerosis and osteoporosis, as it was based on a relatively young population in Finland.

“Alteration in the metabolism of the identified lipid species might contribute to the comorbid conditions and yield new possibilities for their dual-based prevention methods,” concluded the researchers.

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Reference

Mishra BH, Mishra PP, Mononen N, et al. Lipidomic architecture shared by subclinical markers of osteoporosis and atherosclerosis: the Cardiovascular Risk in Young Finns Study. Bone. 2020;131:115160.