The Relationship Between Body Mass Index and Bone Mineral Density: A Mendelian Randomization Study

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ORIGINAL RESEARCH

The Relationship Between Body Mass Index and Bone Mineral Density: A Mendelian Randomization Study Jidong Song1   · Rupeng Zhang1 · Leifeng Lv1 · Jialin Liang1 · Wei Wang1 · Ruiyu Liu1 · Xiaoqian Dang1 Received: 18 March 2020 / Accepted: 21 July 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020

Abstract Body mass index (BMI) is closely associated with bone mineral density (BMD) in both men and women. However, the relationship between BMI and BMD varies according to different studies. Using SNPs strongly associated with BMI in 336,107 individuals, we conducted a two-sample Mendelian randomization study to identify whether and to what extent BMD at different skeletal sites was affected by BMI. A power calculation was also performed. We found that BMI may causally increase lumbar BMD (β 0.087; 95% CI 0.025 to 0.149; P = 0.006) and heel calcaneus BMD (β 0.120; 95% CI 0.082 to 0.157; P = 1 × 10–7). The associations of BMI with forearm and femoral neck BMD were not statistically significant. Our study suggested that higher BMI plays a causal role in increasing BMD and the effects are similar across the skeleton. BMI was causally and positively associated with lumbar and heel calcaneus BMD. However, no statistically significant effects were observed for BMI on femoral neck or forearm BMD. Keywords  Body mass index · Bone mineral density · Mendelian randomization

Introduction

Electronic supplementary material  The online version of this article (https​://doi.org/10.1007/s0022​3-020-00736​-w) contains supplementary material, which is available to authorized users. * Xiaoqian Dang [email protected] Jidong Song [email protected] Rupeng Zhang [email protected] Leifeng Lv [email protected] Jialin Liang [email protected] Wei Wang [email protected] Ruiyu Liu [email protected] 1



Department of Orthopaedics, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an Jiaotong University, No.157, Xiwu Road, Xi’an 710004, Shaanxi, China

Osteoporosis is a common skeletal metabolic disorder characterized by low bone mass, microarchitectural deterioration of bone tissue and an increased risk of fragility fracture. It is a metabolic bone disease occurring in both men and women. The prevalence of osteoporosis or low bone mass is expected to increase from approximately 53 million to more than 70 million by 2030 and the cost of osteoporotic fractures is expected to exceed $25 billion each year by 2025 in the USA [1, 2]. Bone mineral density (BMD), a highly heritable trait [3], is the gold standard for osteoporosis diagnosis. Similar to osteoporosis, obesity is another prevalent public health problem and it has a close clinical association with osteoporosis [4]. Body mass index (BMI) is a simple way of measuring the degree of obesity. BMI is closely associated with BMD in both men and women. However, numerous studies on the relationship between BMI and BMD have found conflicting results. Several studies suggested that obese individuals had low BMD [5, 6]. For example,