Alendronate inhibits bone-specific blood vessels in the femoral metaphyses of mice

To determine whether alendronate affects vascular endothelial cells and regulates the interactions between blood vessels and osteoblasts, we have examined the femoral metaphyses of alendronate-administered mice. Following administration, the bone-specific blood vessels exhibited significantly reduced luminal diameters and rough luminal surfaces with numerous small protrusions and vesicles. Although the osteoclast distribution remained unchanged in alendronate-treated mice, osteoblasts were inactivated in the metaphyseal regions where blood vessels had shrunk. Additionally, the expression of genes such as Ephb4/Efnb2, which mediate vascular endothelial cell–osteoblast interactions, was diminished. Therefore, alendronate may primarily affect bone-specific blood vessels, thus leading to osteoblast inactivation.