BackgroundCoffee is the most commonly consumed beverage among children and adolescences. Caffeine was demonstrated to be associated with bone metabolism. However, the relationship between caffeine intake and BMD in children and adolescents remains unclear. This study aimed to identified relationship between caffeine consumption and bone mineral density (BMD) in children and adolescents.MethodsBased on National Health and Nutrition Examination Survey (NHANES), we conducted an epidemiological cross-section study to measure the relationship between caffeine consumption and BMD in children and adolescents by multivariate linear regression models. Then, five methods of Mendelian randomization (MR) analyses were performed to estimate their causal relationship between coffee and caffeine intake and BMD in children and adolescents. MR-Egger and inverse-variance weighted (IVW) were used to evaluate the heterogeneity effect of instrumental variables (IVs).ResultsIn epidemiological studies, individuals with the highest quartile of caffeine intake do not have a significant change in femur neck BMD (β = 0.0016, 95% CI: -0.0096, 0.0129,P= 0.7747), total femur BMD (β = 0.0019,P= 0.7552), and total spine BMD (β = 0.0081,P= 0.1945) compared with the lowest quartile. In MR analysis, the IVW-random effect indicates no causal relationship between coffee consumption and TB- BMD (β = 0.0034,P= 0.0910). Other methods of MR analyses and sensitivity analysis reveals consistent findings. Similarly, the fixed-effects IVW method shows no causal association between caffeine intake and TB-BMD in children and adolescents (β = 0.0202,P= 0.7828).ConclusionsOur study does not support a causal relationship between caffeine consumption and BMD in children and adolescents. However, more studies are needed to verify our findings, such as its underlying molecular mechanisms and the long-term impact of early caffeine exposure at a younger age.