Background Osteoporosis (OP), characterized by reduced bone mass and microstructural imbalances in bone tissue, is one of the most prevalent bone diseases worldwide. OP imposes a significant societal burden and is influenced by various factors, such as age. However, the causal relationship between OP and waist circumference (WC) remains uncertain. Investigating this relationship is essential for early detection and prevention of at‐risk individuals. Methods This study combined data from the National Health and Nutrition Examination Survey (NHANES) with Mendelian randomization (MR) analysis to examine the association between WC and OP. Baseline characteristics were first analyzed using NHANES data, followed by association, risk stratification, and receiver operating characteristic (ROC) analyses. MR analysis was then conducted and validated through correlation analysis, randomness assessment, and sensitivity testing. Results The NHANES data indicated a significant association between WC and OP, both as an independent factor and after adjusting for various covariates (Model 1: odds ratio (OR) = 0.976, 95% confidence intervals (CIs) = 0.968–0.984, p < 0.001; Model 2: OR = 0.988, 95% CI = 0.979–0.997, p < 0.01; Model 3: OR = 0.985, 95% CI = 0.976–0.994, p < 0.01). In addition, WC exhibited a strong predictive effect on OP (AUC = 0.797). MR analysis identified WC as a protective factor, revealing a significant causal relationship with OP (OR = 0.994, 95% CI = 0.990–0.999, p < 0.05). Rigorous evaluations confirmed these findings, consistent with NHANES results, further reinforcing the association between WC and OP. Conclusion A significant association exists between WC and OP, with the risk decreasing as WC increases. These findings offer valuable insights for future research.
Liu et al. (2026) studied this question.