Medical Science Department, Chugai Pharmaceutical Co., Ltd., Tokyo, Japan.
J Steroid Biochem Mol Biol. 2013 Jul;136:178-82. doi: 10.1016/j.jsbmb.2012.10.004. Epub 2012 Oct 13.
Vitamin D is known as a potent stimulator of bone resorption. The active form of vitamin D3, calcitriol (1α,25-dihydroxyvitamin D3), stimulates release of calcium (Ca) from bone in ex vivo organ culture, and treatment with large amounts of an active vitamin D3 analog induces hypercalcemia and bone resorption in mice in vivo. Calcitriol strongly induces both receptor activator of NF-κB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) in osteoblasts in vitro. On the other hand, it has been reported that active vitamin D3 inhibits bone resorption in various experimental animal models. We previously showed that eldecalcitol [1α,25-dihydroxy-2β-(3-hydroxy-propyloxy)vitamin D3; ED-71] suppresses bone resorption and increases bone mineral density (BMD) to a greater extent than alfacalcidol (1α-hydroxyvitamin D3) in ovariectomized (OVX) rats in vivo. To elucidate the histological events that follow administration of eldecalcitol compared to calcitriol, OVX rats were given either vehicle, eldecalcitol (10, 30, or 90ng/kg), or calcitriol (33.3, 100, 300, or 900ng/kg), and sham-operated control animals were given vehicle, 5-times per week for 12 weeks. The lumbar spine and femur were removed and processed for bone mineral density (BMD) assessments and the femur for histomorphometrical analyzes. Both eldecalcitol and calcitriol increased the lumbar and femoral BMD in a dose dependent manner. Bone histomorphometry revealed that osteoclast surface (Oc.S/BS) and eroded surface (ES/BS) were dose-dependently suppressed in the trabecular region of the femur. Both calcitriol and eldecalcitol dose-dependently stimulated focal bone formation that started without prior bone resorption, a process known as bone minimodeling. Both reduction of bone resorption and stimulation of focal bone formation were more clearly observed in the eldecalcitol-treated rats than in the calcitriol-treated rats. Taken together, these findings suggest that eldecalcitol is a more potent vitamin D3 analog that stimulates focal bone formation (minimodeling) and suppresses bone resorption more strongly than does calcitriol. This article is part of a Special Issue entitled 'Vitamin D Workshop'.
维生素 D 被称为一种强有力的骨吸收刺激物。维生素 D3 的活性形式，1α,25-二羟维生素 D3（calcitriol），在离体器官培养中刺激钙（Ca）从骨中释放，并且用大量的活性维生素 D3 类似物治疗可在体内诱导小鼠高钙血症和骨吸收。Calciriol 在体外强烈诱导成骨细胞中核因子-κB 配体受体激活剂（receptor activator of NF-κB ligand，RANKL）和巨噬细胞集落刺激因子（macrophage colony-stimulating factor，M-CSF）的产生。另一方面，据报道，活性维生素 D3 在各种实验动物模型中抑制骨吸收。我们之前表明， eldecalcitol[1α,25-二羟-2β-（3-羟基丙氧基）维生素 D3；ED-71]在体内比 alfacalcidol（1α-羟维生素 D3）更能抑制去卵巢（OVX）大鼠的骨吸收并增加骨矿物质密度（BMD）。为了阐明与 calcitriol 相比给予 eldecalcitol 后的组织学事件，OVX 大鼠每周给予 5 次 vehicle、eldecalcitol（10、30 或 90ng/kg）或 calcitriol（33.3、100、300 或 900ng/kg），而假手术对照动物给予 vehicle，共 12 周。取出腰椎和股骨进行骨矿物质密度（BMD）评估，并对股骨进行组织形态计量学分析。eldecalcitol 和 calcitriol 均以剂量依赖的方式增加腰椎和股骨 BMD。骨组织形态计量学显示，骨吸收表面（osteoclast surface，Oc.S/BS）和侵蚀表面（eroded surface，ES/BS）在股骨小梁区域呈剂量依赖性抑制。Calcitriol 和 eldecalcitol 均以剂量依赖的方式刺激焦点骨形成，该过程开始时没有先前的骨吸收，这一过程称为骨最小模型。与 calcitriol 治疗的大鼠相比，eldecalcitol 治疗的大鼠更明显地观察到骨吸收减少和焦点骨形成刺激。综上所述，这些发现表明 eldecalcitol 是一种更有效的维生素 D3 类似物，它比 calcitriol 更能刺激焦点骨形成（最小模型）并更强烈地抑制骨吸收。本文是题为“维生素 D 研讨会”的特刊的一部分。
