Bone Abstracts

Eldecalcitol (ED-71; ELD), a 2β-hydroxypropyloxy derivative of 1α,25(OH)2D3, was approved to treat osteoporosis in Japan in 2011. The endothelial protective effect of vitamin D3 in osteoporosis is not clear. This study evaluated the endothelial protective effect of ELD in ovariectomized (OVX) rats.

ELD (20 ng/kg) was orally administered five times a week for 4 weeks from 1 day after OVX surgery. Four weeks after surgery, flow-mediated dilation (FMD) as an indicator of endothelial function was measured by ultrasound in the femoral artery (FA) of living rats and the BMD of the L2–L4 vertebrae was measured by DXA.

FMD was significantly reduced in FA. Nox4 expression and nitrotyrosine content (NT) were increased, indicating oxidative stress, and the eNOS dimer:monomer ratio was decreased, indicating eNOS dysfunction; moreover, PPARγ expression was decreased and NF-κB p65 expression was increased in FA. ELD ameliorated the reduction of FMD. ELD reduced Nox4 and NT and improved the eNOS coupling state and also increased PPARγ expression and decreased NF-κB p65 expression in FA. On the other hand, PPARγ in bone marrow (BM) is a known risk for bone loss, and PPARγ expression was increased in BM. BMD was significantly lower in OVX rats than in sham-operated rats. ELD prevented the reduction of BMD. ELD tended to suppress PPARγ expression in BM. These results suggest that ELD ameliorated endothelial dysfunction in OVX rats. An antioxidative effect via increased PPARγ expression by ELD is thought to improve the eNOS coupling state in FA in this osteoporosis model. Change in PPARγ expression differed between FA and BM in OVX rats, indicating that the effect of ELD on PPARγ signaling might vary according to organ or to disease condition. ELD is expected to act as an anti-osteoporotic agent with the additional value of improving endothelial function in osteoporosis patients.