Department of Orthopedic Surgery, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan.
J Bone Miner Metab. 2010 Jul;28(4):403-9. doi: 10.1007/s00774-009-0148-5. Epub 2010 Jan 26.
Bisphosphonates increase bone mineral density (BMD) by suppressing remodeling space and elongating the duration of mineralization. Menatetrenone (vitamin K(2)) reduces the incidence of fractures by improving bone quality through enhanced gamma-carboxylation of bone glutamic acid residues of osteocalcin in osteoporotic patients. This study investigated the effects of combination treatment with alendronate (ALN) and vitamin K(2) on BMD and bone strength in ovariectomized (OVX) mice. Thirty-three female mice, 16 weeks of age, were assigned to four groups: (1) OVX-control group; (2) oral vitamin K(2) group; (3) subcutaneous ALN group; and (4) ALN + vitamin K(2) group. The treatment was started 4 weeks after OVX and continued for 4 weeks. BMD, geometric parameters measured by peripheral quantitative computed tomography, and mechanical strength at the femoral metaphysis and mid-diaphysis were evaluated after an 8-week treatment period. ALN alone significantly increased total BMD (20%, P < 0.05) and trabecular BMD (25%, P < 0.05), but not the mechanical parameters of the femur, compared with the OVX-control group. Combination treatment with ALN and vitamin K(2) increased not only total BMD (15%, P < 0.05) and trabecular BMD (32%, P < 0.05) but also maximum load (33%, P < 0.05) and breaking energy (25%, P < 0.05) of compression test at the distal metaphysis, and maximum load (20%, P < 0.05) and breaking force (33%, P < 0.05) of three-point bending test at the mid-diaphysis compared with the OVX-control group. These results suggest that ALN, alone or in combination with vitamin K(2), showed significant improvement in BMD, but that the combination treatment was more effective than ALN alone for improving bone strength in OVX mice.
双膦酸盐通过抑制重塑空间和延长矿化时间来增加骨矿物质密度 (BMD)。甲萘醌 (维生素 K(2)) 通过增强骨质疏松症患者骨钙素中骨谷氨酸残基的 γ-羧化作用来提高骨质量，从而降低骨折的发生率。本研究探讨了联合应用阿仑膦酸钠 (ALN) 和维生素 K(2) 对去卵巢 (OVX) 小鼠 BMD 和骨强度的影响。将 33 只 16 周龄雌性小鼠分为四组：(1) OVX 对照组；(2) 口服维生素 K(2) 组；(3) 皮下 ALN 组；和 (4) ALN + 维生素 K(2) 组。OVX 后 4 周开始治疗，持续 4 周。治疗 8 周后评估总 BMD、外周定量计算机断层扫描测量的几何参数以及股骨近段和中段的机械强度。与 OVX 对照组相比，单独使用 ALN 可显著增加总 BMD（20%，P < 0.05）和小梁 BMD（25%，P < 0.05），但不影响股骨的机械参数。ALN 与维生素 K(2) 的联合治疗不仅增加了总 BMD（15%，P < 0.05）和小梁 BMD（32%，P < 0.05），还增加了压缩试验远端骨皮质的最大负荷（33%，P < 0.05）和断裂能（25%，P < 0.05），以及三点弯曲试验中中段的最大负荷（20%，P < 0.05）和断裂力（33%，P < 0.05）与 OVX 对照组相比。这些结果表明，ALN 单独或与维生素 K(2) 联合使用可显著改善 BMD，但联合治疗在改善 OVX 小鼠骨强度方面比单独使用 ALN 更有效。
