Bone effects of vitamin D - Discrepancies between in vivo and in vitro studies

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• 作者：Tatsuo Suda^a ; ^{tasuda@saitama-med.ac.jp} ; Fumiaki Takahashi^b ; Naoyuki Takahashi^c
• 关键词：1伪 ; 25(OH)2D3 ; Bone resorption ; Osteoclast ; Osteoblast ; RANKL
• 刊名：Archives of Biochemistry and Biophysics
• 出版年：2012
• 期刊代码：116_00039861
• 类别：ch
• 出版时间：1 July, 2012
• 卷：523
• 期：1
• 页码：22-29
• 文件大小：717 K

摘要

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 D₃ 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 D₃, 1伪,25-dihydroxyvitamin D₃ [1伪,25(OH)₂D₃] is one of the most potent inducers of receptor activator of NF-魏B ligand (RANKL), a key molecule for osteoclastogenesis, in vitro. In fact, 1伪,25(OH)₂D₃ strongly induced osteoclast formation and bone resorption in vitro. Nevertheless, 1伪,25(OH)₂D₃ and its prodrug, Alfacalcidol (1伪-hydroxyvitamin D₃) 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 [2尾-(3-hydroxypropoxy)-1伪,25(OH)₂D₃], 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.