Assessment of causal association between the socio-economic status and osteoporosis and fractures: a bidirectional Mendelian randomization study in European population.

ABSTRACT

BACKGROUND: The relationship between socio-economic status and bone-related diseases is attracting increasing attention. Therefore, a bidirectional Mendelian randomization (MR) analysis was performed in this study. METHODS: Genetic data on factors associated with socio-economic status (average total household income before tax, years of schooling completed and Townsend Deprivation Index at recruitment), femoral neck bone mineral density (FN-BMD), heel bone mineral density (eBMD), osteoporosis, and five different sites of fracture (spine, femur, lower leg-ankle, foot, and wrist-hand fractures) were derived from genome-wide association summary statistics of European ancestry. The inverse variance weighted method was employed to obtain the causal estimates, complemented by alternative MR techniques, including MR-Egger, weighted median, and MR-pleiotropy residual sum and outlier (MR-PRESSO). Furthermore, sensitivity analyses, and multivariable MR was performed to enhance the robustness of our findings. RESULTS: A higher educational attainment was associated with an increased level of eBMD (beta0.06, 95% CI0.01-0.10, P = 7.24 × 10-3), and decreased risk of osteoporosis (OR0.78, 95% CI0.65-0.94, P = 8.49 × 10-3), spine fracture (OR0.76, 95% CI0.66-0.88, P = 2.94 × 10-4), femur fracture (OR0.78, 95% CI0.67-0.91, P = 1.33 × 10-3), lower leg-ankle fracture (OR0.79, 95% CI0.70-0.88, P = 2.05 × 10-5), foot fracture (OR0.78, 95% CI0.66-0.93, P = 5.92 × 10-3) and wrist-hand fracture (OR0.83, 95% CI0.73-0.95, P = 7.15 × 10-3). Further, material deprivation seemed to harm the spine fracture (OR2.63, 95% CI1.43-4.85, P = 1.91 × 10-3). A higher level of FN-BMD positively affected increased household income (beta0.03, 95% CI0.01-0.04, P = 6.78 × 10-3). All these estimates were adjusted for body mass index (BMI), type 2 diabetes, smoking initiation, and frequency of alcohol intake. CONCLUSIONS: The Mendelian randomization analyses show that higher educational levels is associated with higher eBMD, reduced risk of osteoporosis and fractures, while material deprivation is positively related to spine fracture. Enhanced FN-BMD correlates with increased household income. These findings offer valuable insights into the formulation of health guidelines and policy development.

We conducted stratified analyses to explore the causal links between socio-economic status and osteoporosis and various fractures and observed that education significantly reduced risk of osteoporosis and lower eBMD. It also lowered the risks of fractures of spine, femur, lower leg-ankle, foot, and wrist-hand, while material deprivation exhibited positive associations with spine fracture risk. Bidirectional MR analysis showed that an elevated score of FN-BMD was associated with a higher income level. Our study shows the importance of conducting routine BMD estimations and osteoporosis screening, to enhance knowledge and awareness among individuals to promote bone health and prevent fractures.