title: Bone effects of vitamin D - Discrepancies between in vivo and in vitro studies.
abstract: Vitamin D was discovered as an anti-rachitic agent, but even at present, there is no direct evidence to support the concept that vitamin D directly stimulates osteoblastic bone formation and mineralization. It appears to be paradoxical, but vitamin D functions in the process of osteoclastic bone resorption. In 1952, Carlsson reported that administration of vitamin D(3) to rats fed a vitamin D-deficient, low calcium diet raised serum calcium levels. Since the diet did not contain appreciable amounts of calcium, the rise in serum calcium was considered to be derived from bone. Since then, this assay has been used as a standard bioassay for vitamin D compounds. Osteoclasts, the cells responsible for bone resorption, develop from hematopoietic cells of the monocyte-macrophage lineage. Several lines of evidence have shown that the active form of vitamin D(3), 1α,25-dihydroxyvitamin D(3) [1α,25(OH)(2)D(3)] is one of the most potent inducers of receptor activator of NF-κB ligand (RANKL), a key molecule for osteoclastogenesis, in vitro. In fact, 1α,25(OH)(2)D(3) strongly induced osteoclast formation and bone resorption in vitro. Nevertheless, 1α,25(OH)(2)D(3) and its prodrug, Alfacalcidol (1α-hydroxyvitamin D(3)) have been used as therapeutic agents for osteoporosis since 1983, because they increase bone mineral density and reduce the incidence of bone fracture in vivo. Furthermore, a new vitamin D analog, Eldecalcitol [2β-(3-hydroxypropoxy)-1α,25(OH)(2)D(3)], has been approved as a new drug for osteoporosis in Japan in January 2011. Interestingly, these beneficial effects of in vivo administration of vitamin D compounds are caused by the suppression of osteoclastic bone resorption. The present review article describes the mechanism of the discrepancy of vitamin D compounds in osteoclastic bone resorption between in vivo and in vitro.
authors: Research Center for Genomic Medicine, Saitama Medical University, Saitama 350-1241, Japan. tasuda@saitama-med.ac.jp
authors: Tatsuo
authors: T
authors: Suda
authors: Fumiaki
authors: F
authors: Takahashi
authors: Naoyuki
authors: N
authors: Takahashi
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D002113:Calcification, Physiologic / Q000187:drug effects; D006801:Humans; D006887:Hydroxycholecalciferols / Q000494:pharmacology; D010012:Osteogenesis / Q000187:drug effects; D015203:Reproducibility of Results; D014807:Vitamin D / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology*
chemical_list: D006887:Hydroxycholecalciferols; D014807:Vitamin D; C547512:eldecalcitol; C008088:alfacalcidol