Association Between Serum Apolipoprotein B and Bone Mineral Density and the Effects of Cardiovascular Disease Mediation: Results From the NHANES 2011–2016 and a Mendelian Randomization Study

Background: Previous studies have indicated that blood lipids can influence skeletal health. However, limited research exists on the impact of serum apolipoprotein B (ApoB) on bone mineral density (BMD); meanwhile, it remains unclear to what extent cardiovascular disease plays in...

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Main Authors: Aochuan Sun, Yiduo Chen, Yang Wu, Zhuangzhuang Li, Jingchun Zhang, Zhengtang Liu
Format: Article
Language:English
Published: IMR Press 2025-05-01
Series:Reviews in Cardiovascular Medicine
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Online Access:https://www.imrpress.com/journal/RCM/26/5/10.31083/RCM31395
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author Aochuan Sun
Yiduo Chen
Yang Wu
Zhuangzhuang Li
Jingchun Zhang
Zhengtang Liu
author_facet Aochuan Sun
Yiduo Chen
Yang Wu
Zhuangzhuang Li
Jingchun Zhang
Zhengtang Liu
author_sort Aochuan Sun
collection DOAJ
description Background: Previous studies have indicated that blood lipids can influence skeletal health. However, limited research exists on the impact of serum apolipoprotein B (ApoB) on bone mineral density (BMD); meanwhile, it remains unclear to what extent cardiovascular disease plays in mediating this process. Methods: Therefore, we conducted a cross-sectional analysis involving 2930 participants from the National Health and Nutrition Examination Survey (NHANES) database to explore the relationship between serum ApoB and total body BMD (TB-BMD) and lumbar spine BMD (LS-BMD). We employed a two-step, two-sample Mendelian randomization (MR) analysis using genetic instruments to investigate causality and assess the mediating effects of six cardiovascular diseases. Results: Multivariable linear regression models demonstrated an inverse linear association between serum ApoB and TB-BMD (β = –0.26, 95% confidence interval (CI): –0.41 to –0.12, p < 0.001; p for non-linearity = 0.771) and LS-BMD (β = –0.53, 95% CI: –0.75 to –0.31, p < 0.001; p for non-linearity = 0.164). The primary analysis utilized the multiplicative random effects inverse variance weighted (IVW-MRE) method for the two-sample MR analysis. The results demonstrated a causal relationship between serum ApoB with TB-BMD (β = –0.0424, 95% CI: –0.0746 to –0.0103; p = 0.0096) and LS-BMD (β = –0.0806, 95% CI: –0.1384 to –0.0229; p = 0.0062). The two-step MR analysis indicated heart failure as a mediating factor in the causal relationship between serum ApoB and TB-BMD, with a mediation proportion of 18.69%. Conclusions: The results of this study support that lowering serum ApoB levels could enhance BMD while preventing the occurrence of heart failure might reduce the harm caused by the decrease in BMD due to elevated ApoB levels.
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spelling doaj-art-4a5695c44c2045d39ddaa6c75d23d23a2025-08-20T02:03:25ZengIMR PressReviews in Cardiovascular Medicine1530-65502025-05-012653139510.31083/RCM31395S1530-6550(25)01804-6Association Between Serum Apolipoprotein B and Bone Mineral Density and the Effects of Cardiovascular Disease Mediation: Results From the NHANES 2011–2016 and a Mendelian Randomization StudyAochuan Sun0Yiduo Chen1Yang Wu2Zhuangzhuang Li3Jingchun Zhang4Zhengtang Liu5Graduate School, Beijing University of Chinese Medicine, 100029 Beijing, ChinaGraduate School, Beijing University of Chinese Medicine, 100029 Beijing, ChinaGraduate School, Beijing University of Chinese Medicine, 100029 Beijing, ChinaThe Department of Geriatrics, Xiyuan Hospital, China Academy of Chinese Medical Sciences, 100091 Beijing, ChinaNational Clinical Research Center for Chinese Medicine Cardiology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, 100091 Beijing, ChinaThe Department of Geriatrics, Xiyuan Hospital, China Academy of Chinese Medical Sciences, 100091 Beijing, ChinaBackground: Previous studies have indicated that blood lipids can influence skeletal health. However, limited research exists on the impact of serum apolipoprotein B (ApoB) on bone mineral density (BMD); meanwhile, it remains unclear to what extent cardiovascular disease plays in mediating this process. Methods: Therefore, we conducted a cross-sectional analysis involving 2930 participants from the National Health and Nutrition Examination Survey (NHANES) database to explore the relationship between serum ApoB and total body BMD (TB-BMD) and lumbar spine BMD (LS-BMD). We employed a two-step, two-sample Mendelian randomization (MR) analysis using genetic instruments to investigate causality and assess the mediating effects of six cardiovascular diseases. Results: Multivariable linear regression models demonstrated an inverse linear association between serum ApoB and TB-BMD (β = –0.26, 95% confidence interval (CI): –0.41 to –0.12, p < 0.001; p for non-linearity = 0.771) and LS-BMD (β = –0.53, 95% CI: –0.75 to –0.31, p < 0.001; p for non-linearity = 0.164). The primary analysis utilized the multiplicative random effects inverse variance weighted (IVW-MRE) method for the two-sample MR analysis. The results demonstrated a causal relationship between serum ApoB with TB-BMD (β = –0.0424, 95% CI: –0.0746 to –0.0103; p = 0.0096) and LS-BMD (β = –0.0806, 95% CI: –0.1384 to –0.0229; p = 0.0062). The two-step MR analysis indicated heart failure as a mediating factor in the causal relationship between serum ApoB and TB-BMD, with a mediation proportion of 18.69%. Conclusions: The results of this study support that lowering serum ApoB levels could enhance BMD while preventing the occurrence of heart failure might reduce the harm caused by the decrease in BMD due to elevated ApoB levels.https://www.imrpress.com/journal/RCM/26/5/10.31083/RCM31395apolipoprotein bbone mineral densitynational health and nutrition examination surveymendelian randomizationcardiovascular diseasemediating factor
spellingShingle Aochuan Sun
Yiduo Chen
Yang Wu
Zhuangzhuang Li
Jingchun Zhang
Zhengtang Liu
Association Between Serum Apolipoprotein B and Bone Mineral Density and the Effects of Cardiovascular Disease Mediation: Results From the NHANES 2011–2016 and a Mendelian Randomization Study
Reviews in Cardiovascular Medicine
apolipoprotein b
bone mineral density
national health and nutrition examination survey
mendelian randomization
cardiovascular disease
mediating factor
title Association Between Serum Apolipoprotein B and Bone Mineral Density and the Effects of Cardiovascular Disease Mediation: Results From the NHANES 2011–2016 and a Mendelian Randomization Study
title_full Association Between Serum Apolipoprotein B and Bone Mineral Density and the Effects of Cardiovascular Disease Mediation: Results From the NHANES 2011–2016 and a Mendelian Randomization Study
title_fullStr Association Between Serum Apolipoprotein B and Bone Mineral Density and the Effects of Cardiovascular Disease Mediation: Results From the NHANES 2011–2016 and a Mendelian Randomization Study
title_full_unstemmed Association Between Serum Apolipoprotein B and Bone Mineral Density and the Effects of Cardiovascular Disease Mediation: Results From the NHANES 2011–2016 and a Mendelian Randomization Study
title_short Association Between Serum Apolipoprotein B and Bone Mineral Density and the Effects of Cardiovascular Disease Mediation: Results From the NHANES 2011–2016 and a Mendelian Randomization Study
title_sort association between serum apolipoprotein b and bone mineral density and the effects of cardiovascular disease mediation results from the nhanes 2011 2016 and a mendelian randomization study
topic apolipoprotein b
bone mineral density
national health and nutrition examination survey
mendelian randomization
cardiovascular disease
mediating factor
url https://www.imrpress.com/journal/RCM/26/5/10.31083/RCM31395
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