Iwamoto Jun, Takeda Tsuyoshi, Ichimura Shoichi
Department of Sports Medicine, School of Medicine, Keio University, Tokyo, Japan.
Keio J Med. 2003 Sep;52(3):147-50. doi: 10.2302/kjm.52.147.
It is established in Japan that treatment with 1alpha-hydroxyvitamin D3 (alfacalcidol) slightly reduces bone turnover, sustains lumbar bone mineral density (BMD), and prevents osteoporotic vertebral fractures in postmenopausal women with osteoporosis, while vitamin K2 (menatetrenone) enhances gamma-carboxylation of bone glutamic acid residues and secretion of osteocalcin, sustains lumbar BMD, and prevents osteoporotic fractures in patients with osteoporosis. Available evidence suggests that the effect of vitamin K2 on mineralization by human periosteal osteoblasts is enhanced in the presence of 1,25 dihydroxyvitamin D3 in vitro. The effect of vitamin K2 on BMD in ovariectomized rats is affected by the plasma 25-hydroxyvitamin D3 level in vivo, and is significant only when rats are fed a diet containing vitamin D3. Based on this line of evidence, combined treatment with alfacalcidol and menatetrenone for osteoporosis is surmised to be more effective than treatment with menatetrenone alone, and may have anabolic effects on osteoporotic bone. This combined treatment may increase bone formation as well as bone resorption over the mild anti-resorptive effect of alfacalcidol itself, and shows the greatest effect on lumbar BMD or the incidence of vertebral fractures in studies in which the mean age and years since menopause of subjects were low and the degree of osteoporosis was mild. It may be effective for mild postmenopausal osteoporosis in which age-related deterioration of trabecular bone properties remains below the threshold for vertebral fractures, even if bone resorption is increased and trabecular bone has deteriorated.
在日本已证实,用1α-羟基维生素D3(阿法骨化醇)治疗可轻微降低骨转换率,维持腰椎骨矿物质密度(BMD),并预防绝经后骨质疏松症女性的骨质疏松性椎体骨折,而维生素K2(甲萘醌)可增强骨谷氨酸残基的γ-羧化作用及骨钙素的分泌,维持腰椎BMD,并预防骨质疏松症患者的骨质疏松性骨折。现有证据表明,在体外1,25-二羟基维生素D3存在的情况下,维生素K2对人骨膜成骨细胞矿化的作用会增强。维生素K2对去卵巢大鼠骨密度的影响在体内受血浆25-羟基维生素D3水平的影响,且只有在给大鼠喂食含维生素D3的饮食时才显著。基于这一系列证据,推测阿法骨化醇和甲萘醌联合治疗骨质疏松症比单独使用甲萘醌治疗更有效,并且可能对骨质疏松性骨有合成代谢作用。这种联合治疗可能会增加骨形成以及超过阿法骨化醇本身轻微抗吸收作用的骨吸收,并且在受试者平均年龄和绝经后年限较低且骨质疏松程度较轻的研究中,对腰椎BMD或椎体骨折发生率显示出最大效果。即使骨吸收增加且小梁骨已退化,但对于年龄相关的小梁骨特性恶化仍低于椎体骨折阈值的轻度绝经后骨质疏松症可能有效。