Current Topics on Vitamin D. The role of active forms of vitamin D in regulation of bone remodeling

Abstract

Active forms of vitamin D3 have been widely used in the treatment of rickets, osteomalacia, and osteoporosis in order to stimulate bone mineralization and prevent bone loss. Meanwhile, the active form of vitamin D3, 1α, 25-dihydroxyvitamin D3 [1α, 25 (OH) 2D3], upregulates expression of receptor activator of nuclear factor-κB ligand (RANKL) in osteoblastic cells. Osteoclast formation requires RANKL and macrophage colony-stimulating factor (M-CSF), which are expressed in osteoblastic cells. Recently, IL-34 was discovered as a cytokine functionally overlapping M-CSF. We found that administration of 1α, 25 (OH) 2D3 into mice enhanced IL-34 expression in spleen and bone. These results suggest that 1α, 25 (OH) 2D3 is a bone resorption-stimulating factor. However, daily administration of an active vitamin D3 analog (eldecalcitol, an osteoporotic therapeutic drug) for a month suppressed RANKL expression in osteoblasts, resulting in suppression of bone resorption. Here we discuss new findings and hypotheses to explain this contradictory effect of active vitamin D3 on bone remodeling.