Sato Yoshihiro, Honda Yoshiaki, Umeno Kazuo, Hayashida Norimasa, Iwamoto Jun, Takeda Tsuyoshi, Matsumoto Hideo
Department of Neurology, Mitate Hospital, Japan.
Kurume Med J. 2011;57(4):117-24. doi: 10.2739/kurumemedj.57.117.
A high incidence of fractures, particularly of the hip, represents an important problem in patients with Alzheimer disease (AD), who are prone to falls and have osteoporosis. We previously found that vitamin K deficiency and low 25-hydroxyvitamin D (25-OHD) with compensatory hyperparathyroidism cause reduced bone mineral density (BMD) in female patients with AD. This may modifiable by intervention with menatetrenone (vitamin K2) and risedronate sodium; we address the possibility that treatment with menatetrenone, risedronate and calcium may reduce the incidence of nonvertebral fractures in elderly patients with AD. A total of 231 elderly patients with AD were randomly assigned to daily treatment with 45 mg of menatetrenone or a placebo combined with once weekly risedronate sodium, and followed up for 12 months. At baseline, patients of both groups showed high undercarboxylated osteocalcin (ucOC) and low 25-OHD insufficiency with compensatory hyperparathyroidism. During the study period, BMD in the treatment group increased by 5.7% and increased by 2.1% in the control group. Nonvertebral fractures occurred in 15 patients (10 hip fractures) in the control group and 5 patients (2 hip fractures) in the treatment group. The relative risk in the treatment group compared with the control group was 0.31 (95% confidence interval, 0.12-0.81). Elderly AD patients with hypovitaminosis K and D are at increased risk for hip fracture. The study medications were well tolerated with relatively few adverse events and effective in reducing the risk of a fracture in elderly patients with AD.
骨折发生率高，尤其是髋部骨折，是阿尔茨海默病（AD）患者的一个重要问题，这类患者容易跌倒且患有骨质疏松症。我们之前发现，维生素K缺乏以及伴有代偿性甲状旁腺功能亢进的低25-羟维生素D（25-OHD）会导致女性AD患者骨密度（BMD）降低。这可能通过甲萘醌（维生素K2）和利塞膦酸钠干预来改善；我们探讨了甲萘醌、利塞膦酸和钙联合治疗能否降低老年AD患者非椎体骨折发生率的可能性。总共231例老年AD患者被随机分配，分别接受每日45毫克甲萘醌或安慰剂治疗，并联合每周一次的利塞膦酸钠，随访12个月。基线时，两组患者均表现出高未羧化骨钙素（ucOC）以及伴有代偿性甲状旁腺功能亢进的低25-OHD不足。在研究期间，治疗组的骨密度增加了5.7%，而对照组增加了2.1%。对照组有15例患者发生非椎体骨折（10例髋部骨折），治疗组有5例患者发生非椎体骨折（2例髋部骨折）。治疗组与对照组相比的相对风险为0.31（95%置信区间，0.12 - 0.81）。维生素K和D缺乏的老年AD患者髋部骨折风险增加。研究药物耐受性良好，不良事件相对较少，并且在降低老年AD患者骨折风险方面有效。
