The impact of alcohol consumption on bone mineral density: Insights from cross-sectional and Mendelian randomization studies

Introduction Alcohol use is widely prevalent across different regions and cultural settings worldwide. While prior studies have suggested a positive impact of light alcohol consumption on bone mineral density (BMD), the relationship between different levels of alcohol consumption and BMD remains controversial. This study conducted cross-sectional analyses within the Rotterdam Study (RS) and UK Biobank (UKB) to examine this association, followed by one- and two-sample Mendelian randomization (MR) to assess potential causality. Methods This study included 4087 Europeans from the Rotterdam Study and 29,856 from the UK Biobank. In the cross-sectional analyses, multilinear regression was used to examine the association between alcohol consumption (g/day) and bone outcomes [i.e., bone mineral density (BMD) and trabecular bone score (TBS)]. For MR analyses, genetic variants associated with alcohol consumption and problematic alcohol use [defined as a combination of alcohol use disorders (AUD), alcohol dependence, and measures of Alcohol Use Disorders Identification Test–Problems (AUDIT-P)] were used as the instrumental variable (IV) for both exposures in both one- and two-sample MR. Results Cross-sectional analyses revealed a positive relationship between alcohol consumption and lumbar spine BMD (LS-BMD) (RS: β = 0.108, p = 0.009; UKB: β = 0.095, p = 6.87 × 10 −13 ), femoral neck BMD (FN-BMD) (RS: β = 0.140, p = 0.001; UKB: β = 0.102, p = 3.42 × 10 −15 ), and lumbar spine TBS (LS-TBS) (RS: β = 0.128, p = 0.004; UKB: β = 0.084, p = 6.53 × 10 −07 ) in both studies, while alcohol consumption was only significantly associated with total body BMD (TB-BMD) (RS: β = 0.059, p = 0.087; UKB: β = 0.058, p = 7.48 × 10 −9 ) in UKB. However, both one-sample and two-sample MR analyses found no evidence for a causal effect of genetically predicted alcohol consumption or problematic alcohol consumption on bone outcomes. Conclusion In two independent studies, we observed a positive cross-sectional association of alcohol consumption with femoral neck BMD, lumbar spine BMD and TBS in European participants. However, MR findings did not demonstrate a causal link, suggesting that other factors or biases may confound the observed positive relationship. Further research is warranted to better understand the underlying mechanisms and potential confounders of this association.