Associations of bone mass and polygenic risk of osteoporosis with indicators of arterial wall condition

Background: The identification of genetic factors that are simultaneously responsible for the predisposition to the development of cardiovascular diseases (CVD) and osteoporosis (OP) is important for the prevention of both conditions.

Aim: The aim of this study is to evaluate three genetic risk scales (GRS) that previously showed an association with bone mineral density (BMD) and fracture risk, as well as to study the associations of these GRS with vascular wall pathology.

Materials and methods: 250 female outpatients (aged 45 to 69) were enrolled into a cross-sectional study. The intima-media thickness (IMT), the presence and number of atherosclerotic plaques (AP) were studied using duplex scanning. Pulse wave velocity (PWV), augmentation index (AI) were measured by applanation tonometry. Coronary vessels calcium deposits were registered by multispiral computed tomography (MSCT) using the Agatston calcium index (CI). The BMD of the spine, hip neck (HN) and proximal hip (PH) was measured using double energy x-ray absorptiometry. Bone resorption marker type-1 collagen C-terminal telopeptide (CTx) was assessed solid-phase enzyme immunoassay. The genetic study included DNA extraction from whole blood samples. Targeted sequencing was performed on the Nextseq550 sequencer (Illumina, USA). Statistical analysis was carried out using the SAS software package for Windows, version 9.0 (SAS Institute Inc., USA).

Results: The chance of detecting low bone mass increased more than 4 times at values of IMT ≥0.9 mm (OR=4.17; 95%CI [1.2–14.4], p<0.02), 2.4 times in the presence of AP in the carotid arteries (OR=2.45; 95%CI [1.12–4.88], p><0.05), by 6.7 times with an Agatstone CI ≥ 100 units (OR=6.68; 95%CI [1.56–28.7], p><0.001), 1.4 times (OR=1.43; 95%CI [0.56–3.68], p><0.438) with a PWV ≥10 m/s, 1.2 times (OR=1.2; 95%CI [0.601–2.43], p><0.60) with increased AI ≥ 27%. According to multivariate linear regression analysis (adjusted for age, duration of postmenopause, marker of bone resorption CTx), a significant association of all GRS with BMD in all parts of the skeleton was revealed. Both univariate and multivariate regression models adjusted for several covariants (age, total cholesterol, systolic blood pressure) showed a reliable association of GRS62 with the presence of plaques and GRS63 — with coronary artery CI. Conclusion: The results of the study demonstrated the association of polygenic genetic risk of GRS-based OP with BMD and vascular wall status indicators in women in the peri and postmenopausal periods.>< 0.02), 2.4 times in the presence of AP in the carotid arteries (OR=2.45; 95%CI [1.12–4.88], p< 0.05), by 6.7 times with an Agatstone CI ≥ 100 units (OR=6.68; 95%CI [1.56–28.7], p< 0.001), 1.4 times (OR=1.43; 95%CI [0.56–3.68], p< 0.438) with a PWV ≥10 m/s, 1.2 times (OR=1.2; 95%CI [0.601–2.43], p<0.60) with increased AI ≥ 27%. According to multivariate linear regression analysis (adjusted for age, duration of postmenopause, marker of bone resorption CTx), a significant association of all GRS with BMD in all parts of the skeleton was revealed. Both univariate and multivariate regression models adjusted for several covariants (age, total cholesterol, systolic blood pressure) showed a reliable association of GRS62 with the presence of plaques and GRS63 — with coronary artery CI.>< 0.60) with increased AI ≥ 27%. According to multivariate linear regression analysis (adjusted for age, duration of postmenopause, marker of bone resorption CTx), a significant association of all GRS with BMD in all parts of the skeleton was revealed. Both univariate and multivariate regression models adjusted for several covariants (age, total cholesterol, systolic blood pressure) showed a reliable association of GRS62 with the presence of plaques and GRS63 — with coronary artery CI.

Conclusion: The results of the study demonstrated the association of polygenic genetic risk of GRS-based OP with BMD and vascular wall status indicators in women in the peri and postmenopausal periods.

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