The association of smoking on the increased risk of osteoporotic fracture: Results from a cross-sectional study and two-sample Mendelian randomization

INTRODUCTION We conducted analyses of the association between smoking and osteoporosis and osteoporotic fractures using a secondary dataset analysis of the National Health and Nutrition Examination Survey (NHANES) database and the two -sample Mendelian randomization (MR) method. METHODS The associations between smoking and osteoporosis or osteoporotic fractures were analyzed using weighted logistic regression models for both univariate and multivariable analyses using pooled 1999-2018 NHANES data. The summary -level data of genome-wide association studies (GWAS) of smoking and osteoporosis were extracted from the IEU Open GWAS project. The inverse variance weighted method was used as the main method for the two -sample MR analysis. RESULTS We obtained the following main findings based on the NHANES data: smoking was associated with osteoporosis according to the analyses of 30856 participants (OR=1.21; 95% CI: 1.06-1.39, p=0.004); smoking was associated with hip osteoporotic fracture according to the analyses of 30928 participants (OR=1.47; 95% CI: 1.14-1.90, p=0.004); smoking was associated with wrist osteoporotic fracture according to the analyses of 30923 participants (OR=1.33; 95% CI: 1.18-1.49, p<0.001); and smoking was associated with spine osteoporotic fracture according to the analyses of 30910 participants (OR=1.43, 95% CI: 1.18- 1.73, p<0.001). In addition, we confirmed the potential causal effect of smoking on the risk of osteoporotic fracture (OR=24.5; 95% CI: 1.11-539, p=0.043) by conducting two -sample MR analyses. CONCLUSIONS Smoking was associated with increased risks of both osteoporosis and osteoporotic fracture. Smoking showed a potential causal effect on the risk of osteoporotic fracture.