Causal effects of osteoporosis on structural changes in specific brain regions: a Mendelian randomization study

Observational studies have reported that osteoporosis is associated with cortical changes in the brain. However, the inherent limitations of observational studies pose challenges in eliminating confounding factors and establishing causal relationships. And previous observational studies have not reported changes in specific brain regions. By employing Mendelian randomization, we have been able to infer a causal relationship between osteoporosis and a reduction in the surficial area (SA) of the brain cortical. This effect is partially mediated by vascular calcification. We found that osteoporosis significantly decreased the SA of global brain cortical (β = -1587.62 mm2, 95%CI: -2645.94 mm2 to -529.32 mm2, P = 0.003) as well as the paracentral gyrus without global weighted (β = - 19.42 mm2, 95%CI: -28.90 mm2 to -9.95 mm2, P = 5.85 × 10-5). Furthermore, we estimated that 42.25% and 47.21% of the aforementioned effects are mediated through vascular calcification, respectively. Osteoporosis leads to a reduction in the SA of the brain cortical, suggesting the presence of the bone-brain axis. Vascular calcification plays a role in mediating this process to a certain extent. These findings establish a theoretical foundation for further investigations into the intricate interplay between bone, blood vessels, and the brain.