Vitamin D was discovered as an anti-rachitic agent preventing a failure in bone mineralization, but it is now established that the active form of
vitamin D3 (1α,25(
OH)2D3) induces
bone resorption. Discovery of the receptor activator of nuclear factor -κB
ligand (RANKL) uncovered the molecular mechanism by which 1α,25(
OH)2D3 stimulates
bone resorption. Treating osteoblastic cells with 1α,25(
OH)2D3 stimulates RANKL expression, which in turn induces osteoclastogenesis. Nevertheless, active
vitamin D compounds such as
calcitriol (1α,25(
OH)2D3),
alfacalcidol (1α(
OH)D3) and
eldecalcitol (1α,25-dihydroxy-2β-(3-hydroxypropoxy) vitamin D3) have been used as therapeutic drugs for
osteoporosis, as they increase bone mineral density (BMD) in osteoporotic patients. Paradoxically, the increase in BMD is caused by the suppression of
bone resorption. Several studies have been performed to elucidate the mechanism by which active
vitamin D compounds suppress
bone resorption in vivo. Our study showed that daily administration of
eldecalcitol to mice suppressed neither the number of osteoclast precursors in the bone marrow nor the number of osteoclasts formed in ex vivo cultures.
Eldecalcitol administration suppressed RANKL expression in osteoblasts. This review discusses how the difference between in vitro and in vivo effects of active
vitamin D compounds on
bone resorption is induced.