Keller-Baruch J, et al. - To investigate whether genetically reduced circulating vascular endothelial growth factor (VEGF) was correlated with reduced BMD and elevated risk of fracture, researchers performed a a two-sample Mendelian randomization study. A sum of 76,549 cases and 470,164 controls were selected for this meta-analysis. They applied summary statistics from a genomewide association study meta-analysis of circulating VEGF level to diagnose 10 genetic variants explaining up to 52% of the variance in circulating VEGF levels. There was no correlation between genetically lowered circulating VEGF and a reduce in BMD or elevated risk of fracture, indicating that efforts to influence circulating VEGF level are unlikely to have significant impacts on osteoporosis results and that previous observational correlation of circulating VEGF with BMD were changed by confounding or reverse causation.