Body mass index and the risk of low bone mass–related fractures in women compared with men

Xiang, Bingyan; Huang, Wei; Zhou, Guoqing; Hu, Ning; Chen, Hong; Chen, Cheng

doi:10.1097/md.0000000000005290

Cited by 35 publications

(17 citation statements)

References 52 publications

(70 reference statements)

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“…all traits known to increase in individuals with higher BMI [26][27][28][29] . The extent to which these secondary phenotypes reflect causal associations between genetic risk and disease is unclear due to the commonality of co-morbidity of these traits.…”

Section: Discussionmentioning

confidence: 99%

Polygenic Risk Scores for Cardio-renal-metabolic Diseases in the Penn Medicine Biobank

Kember

Verma

et al. 2019

Preprint

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Cardio-renal-metabolic (CaReMe) conditions are common and the leading cause of mortality around the world. Genome-wide association studies have shown that these diseases are polygenic and share many genetic risk factors. Identifying individuals at high genetic risk will allow us to target prevention and treatment strategies. Polygenic risk scores (PRS) are aggregate weighted counts that can demonstrate an individual's genetic liability for disease. However, current PRS are often based on European ancestry individuals, limiting the implementation of precision medicine efforts in diverse populations. In this study, we develop PRS for six diseases and traits related to cardio-renal-metabolic disease in the Penn Medicine Biobank. We investigate their performance in both European and African ancestry individuals, and identify genetic and phenotypic overlap within these conditions. We find that genetic risk is associated with the primary phenotype in both ancestries, but this does not translate into a model of predictive value in African ancestry individuals. We conclude that future research should prioritize genetic studies in diverse ancestries in order to address this disparity.Recent studies show high prevalence of cardio-renal-metabolic conditions among adults in the USA 4 and together they are the leading cause of mortality around the world 5,6 . GWAS have identified more than 100 loci associated with common diseases such as coronary artery disease (CAD), body mass index (BMI), hypertension, renal failure and type 2 diabetes (T2D). This group of cardio, renal, and metabolic conditions are collectively referred to as CaReMe conditions. Among the individuals that are diagnosed with one disease (for example T2D), the prevalence of comorbidities such as hypertension, CAD, heart failure (HF), and chronic kidney disease (CKD) also increases. To evaluate disease risk in an individual, it is essential to also consider comorbid or secondary conditions related to the primary disease. There are several GWA-studies that have identified shared genetic associations between CaReMe conditions, demonstrating similarity in the underlying genetic architecture 7,8 . Pathophysiology of these conditions also show the cross-talk between organ systems and its effect on disease progression such as hemodynamic interaction between heart and kidney in heart failure 9 . With PRS, we can derive individuals' disease risk for each CaReMe condition using GWAS summary statistics. More importantly, PRS is derived from the effect of millions of genetic variants on a disease; so it accounts for an individual's genetic background. Therefore, PRS can evaluate the genetic overlap among coexisting or comorbid conditions. Phenome-wide Association Studies (PheWAS) can be used to identify links between disease risk and other conditions 10-12 . Using these strategies, we investigated whether cross-phenotype associations can provide insights into the contribution of risk for one disease risk on other conditions. Lastly, we also evaluated the effect of age, s...

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Section: Discussionmentioning

confidence: 99%

Polygenic Risk Scores for Cardio-renal-metabolic Diseases in the Penn Medicine Biobank

Kember

Verma

et al. 2019

Preprint

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“…In osteoporosis research, animal models have been used for more than a century and have helped to elucidate the underlying disease mechanisms and explore new targets for treatment. Since several risk factors have been associated with osteoporosis like age [22], menopausal status [23], hormonal dysregulation [24], malabsorption [25], side effects to medication like prednisolone [26], smoking [27], low BMI [28], immobilization [29], and disuse [30], it is crucial to select the appropriate animal model. Previous studies have revealed that the magnitude of bone loss varies between the different models used [7,11,31].…”

Section: Discussionmentioning

confidence: 99%

Animal models of disuse-induced bone loss: study protocol for a systematic review

2020

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Background: Disuse is a cardinal sign of various neurological diseases like stroke, cerebral palsy, and amyotrophic lateral sclerosis. Disuse leads to reduced mechanical loading of the skeleton, and a substantial and significant loss of bone mass quickly materializes. Several animal models have been proposed to investigate the pathogenesis of disuse-induced bone loss and to test new pharmaceutical targets to counteract it. As animal models may overcome several of the limitations in observational studies conducted in patients and allow for measurements not possible in humans, the primary objective of the present study is to provide a comprehensive overview of the available animal models of disuse-induced bone loss. Methods/design: This is a protocol for a systematic review of animal models of disuse-induced bone loss. An exhaustive search will be performed on PubMed and Embase in order to identify relevant studies. The primary outcome will be the method of disuse induction. The secondary outcomes will be related to bone samples and anatomical sites investigated, methods used to analyze and quantify bone loss, and bibliographic information. The protocol adheres to the current guiding principles of the Preferred Reporting Items for Systematic Review and Meta-analysis Protocols (PRISMA-P) 2015 statement. Extracted data will be analyzed with descriptive statistics, and all the methods used to induce disuse will be described in detail with a narrative synthesis. Discussion: This systematic review will provide an overview of available animal models of disuse-induced bone loss and discuss the different methods used to quantify and analyze the bone loss. Since bone loss caused by disuse is a hallmark of various diseases from different medical specialties, this overview will be of great benefit for all researchers planning to conduct disuse animal studies in the future. Systematic review registration: PROSPERO CRD42020157452.

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“…This may be the reason for the insignificant effects of healthy behaviors on WC and other MRFs in the underweight subgroup. Nevertheless, underweight individuals have been found to be associated with a high risk of health-related problems such as osteoporosis, infection, and decreased immune function [ 59 , 60 ]. Therefore, the needs of workplace health promotion for underweight individuals should be targeted in different ways.…”

Section: Discussionmentioning

confidence: 99%

Health-Associated Nutrition and Exercise Behaviors in Relation to Metabolic Risk Factors Stratified by Body Mass Index

Huang

et al. 2019

IJERPH

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This study aimed to investigate the relationships of nutrition and exercise behaviors on metabolic risk factors (MRF) when body mass index (BMI) was considered. Health-associated nutrition and exercise behaviors were assessed by a questionnaire, anthropometric values, blood pressure and biochemical determinations that were obtained from 4017 workers. The nutrition score was negatively associated with triglycerides in the overweight subgroup and with systolic blood pressure (SBP) in the obese subgroup. The exercise score was negatively associated with triglycerides and waist circumference (WC) and positively associated with SBP and high-density lipoprotein cholesterol (HDL-C) in the ideal weight subgroup as well as being negatively associated with WC and positively associated with HDL-C in the overweight subgroup. Similarly, the exercise score was negatively associated with WC and positively associated with SBP in the obese subgroup. However, no significant association was found between nutrition or exercise behavior and MRF in the underweight subgroup. In conclusion, the relationships of exercise and nutrition behaviors on MRF varied for different levels of BMI. Exercise showed a significant association with lower WC. Moreover, its effect showed a gradient trend in accordance with the levels of BMI. For ameliorating MRF, exercise seemed to have better effects than nutrition behavior, especially in the ideal weight subgroup.

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Body mass index and the risk of low bone mass–related fractures in women compared with men

Cited by 35 publications

References 52 publications

Polygenic Risk Scores for Cardio-renal-metabolic Diseases in the Penn Medicine Biobank

Polygenic Risk Scores for Cardio-renal-metabolic Diseases in the Penn Medicine Biobank

Animal models of disuse-induced bone loss: study protocol for a systematic review

Health-Associated Nutrition and Exercise Behaviors in Relation to Metabolic Risk Factors Stratified by Body Mass Index

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