Protective Effects of Bone Mineral Density on Age-Related Macular Degeneration: A Mendelian Randomization Study

Observational studies have established the connection between a decrease in bone mineral density (BMD) and an increased susceptibility to age-related macular degeneration (AMD). However, the cause-and-effect link of this correlation remains uncertain. This study employed Mendelian randomization (MR) methods to examine the causality between BMDs and AMD.

The GEnetic Factors for OSteoporosis (GEFOS) Consortium, UK Biobank, and FinnGen Biobank offered summary statistics for BMD and AMD. We adopted an array of quality control procedures to screen for eligible instrumental single nucleotide polymorphisms (SNPs). The inverse variance weighting (IVW) algorithm was the most trustworthy approach in MR analyses. Furthermore, we employed additional analytical methods such as MR-Egger and weighted median (WM) for confirming the soundness of the present MR outcomes.

The findings indicated that genetically predicted total body BMD (TB-BMD, IVW: OR = 0.772, 95% CI = 0.642-0.928, p = 0.006), lumbar spine BMD (LS-BMD, IVW: OR = 0.739, 95% CI = 0.583-0.937, p = 0.013), femoral neck (FN-BMD, WM: OR = 0.626, 95% CI = 0.432-0.906, p = 0.013), and TB-BMD (age over 60, MR-Egger, OR = 0.383, 95% CI = 0.163-0.902, p = 0.041) were associated with lower odds of wet AMD. No significant causal relationship can be found between other BMDs and Wet-AMD, or between BMDs and Dry-AMD.

Our MR analysis supported the causal correlation between genetically predicted BMD and Wet-AMD. As to Dry-AMD, it was not causally related to BMD. Our study complemented the evidence from previous observational surveys and emphasized the extraordinary importance of monitoring BMD for preventing and treating AMD.