Associations of Anthropometric Indicators with Bone Mineral Density and the Risk of Bone Fractures and Falls: A Large-Scale Genetic Correlation Study

Abstract

Introduction: Although observational studies have suggested potential associations between Anthropometric Indicators (AIs), Osteoporosis (OP), and bone fractures, the causal links are still scarce. This study aimed to comprehensively evaluate the causal relationships between five AIs and site- and age-specific Bone Mineral Density (BMD), as well as bone fractures and falls.

Methods: Genetic exposure data for AIs and outcome data for BMD, bone fractures, and falls were retrieved from various genetic consortia. Genome-wide associations of Single-Nucleotide Polymorphisms (SNPs) were selected as Instrumental Variables (IVs) to infer causal effects in univariable and multivariable Mendelian Randomization (MR) analyses.

Results: The results of primary univariable MR analyses revealed that a per-unit increase in Hip Circumference (HC) was causally associated with a lower risk of bone fractures (Inverse Variance Weighting [IVW] method: OR = 0.80, 95% CI: 0.74, 0.88; P = 1.73×10^-06). After adjusting for Body Mass Index (BMI), smoking, and alcohol consumption, further Multivariable Mendelian Randomization (MVMR) analysis supported the presence of causal effects of HC on the decreased risk of fractures. Nevertheless, no causal associations were found between Neck Circumference (NC), Waist Circumference (WC), Waist-to-Hip Ratio (WHR), or Intracranial Volume (ICV) and site/age-specific BMD or the risk of bone fractures or falls.

Discussion: Genetic MR analysis establishes HC as an independent protective factor against fractures, resolving prior observational evidence. Limitations include European ancestry bias.

Conclusion: This study reveals an independent causal association between HC and a lower risk of bone fractures, suggesting that an appropriate increase in HC is beneficial for the prevention of OP.

Keywords: Anthropometric indicator; bone fractures.; bone mineral density; mendelian randomization; osteoporosis.