JCI：维生素D对骨质疏松症的双刃剑作用

维生素D有强筋骨作用，是调节血钙水平的关键。钙主要是通过饮食获得，钙通过肠道吸收进入血流。除了促进骨骼强健外，钙是多种重要生理过程的必需物质。维生素D存在骨和肠细胞受体中，该受体具有调节血液中钙的水平，并决定钙在骨骼中储存多少。最近的几项临床试验研究证实维生素D补充剂对中老年人由预防骨折的功效，然而这些试验的结果并没有对这些补充剂的功效达成一个共识。

在这一月的JCI的杂志上，比利时鲁汶大学Geert Carmeliet博士和同事研究了当血钙水平枯竭时，维生素D如何影响骨骼的。使用缺乏肠道维生素D受体的小鼠，研究人员发现小鼠仍然有正常的血钙水平，即使在给予低钙饮食后。另外实验也表明维生素D刺激骨细胞产生促进钙移出骨骼的因素，钙移出骨骼以维持正常的血钙水平。因此维生素D维持血钙水平是非常重要的，它可以促进骨质密度的损失。

在随后的文章评论中，北卡罗莱纳州达勒姆市杜克大学医学中心Cathleen Colón-Emeric博士和Kenneth Lyles博士讨论了本次研究结果的临床意义，以及如何将这些实验发现用于解释临床试验结果，临床上维生素D补充剂有时能防止中老年患者骨折，但在某些情况下却会增加骨折发生率。（生物谷：Bioon.com）

doi:10.1172/JCI45890
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Normocalcemia is maintained in mice under conditions of calcium malabsorption by vitamin D–induced inhibition of bone mineralization

Liesbet Lieben1, Ritsuko Masuyama1, Sophie Torrekens1, Riet Van Looveren1, Jan Schrooten2, Pieter Baatsen3, Marie-Hélène Lafage-Proust4, Tom Dresselaers5, Jian Q. Feng6, Lynda F. Bonewald7, Mark B. Meyer8, J. Wesley Pike8, Roger Bouillon1 and Geert Carmeliet1

Serum calcium levels are tightly controlled by an integrated hormone-controlled system that involves active vitamin D [1,25(OH)2D], which can elicit calcium mobilization from bone when intestinal calcium absorption is decreased. The skeletal adaptations, however, are still poorly characterized. To gain insight into these issues, we analyzed the consequences of specific vitamin D receptor (Vdr) inactivation in the intestine and in mature osteoblasts on calcium and bone homeostasis. We report here that decreased intestinal calcium absorption in intestine-specific Vdr knockout mice resulted in severely reduced skeletal calcium levels so as to ensure normal levels of calcium in the serum. Furthermore, increased 1,25(OH)2D levels not only stimulated bone turnover, leading to osteopenia, but also suppressed bone matrix mineralization. This resulted in extensive hyperosteoidosis, also surrounding the osteocytes, and hypomineralization of the entire bone cortex, which may have contributed to the increase in bone fractures. Mechanistically, osteoblastic VDR signaling suppressed calcium incorporation in bone by directly stimulating the transcription of genes encoding mineralization inhibitors. Ablation of skeletal Vdr signaling precluded this calcium transfer from bone to serum, leading to better preservation of bone mass and mineralization. These findings indicate that in mice, maintaining normocalcemia has priority over skeletal integrity, and that to minimize skeletal calcium storage, 1,25(OH)2D not only increases calcium release from bone, but also inhibits calcium incorporation in bone.