Tanaka Shiro, Miyazaki Teruhiko, Uemura Yukari, Kuroda Tatsuhiko, Miyakawa Nobuaki, Nakamura Toshitaka, Fukunaga Masao, Ohashi Yasuo, Ohta Hiroaki, Mori Satoshi, Hagino Hiroshi, Hosoi Takayuki, Sugimoto Toshitsugu, Itoi Eiji, Orimo Hajime, Shiraki Masataka
Department of Pharmacoepidemiology, Graduate School of Medicine and Public Health, Kyoto University, Kyoto, Japan,
J Bone Miner Metab. 2014 May;32(3):298-304. doi: 10.1007/s00774-013-0491-4. Epub 2013 Jul 5.
Concurrent treatments with bisphosphonates and vitamin K are promising given that bisphosphonates possibly interfere with vitamin K activation. This is a prospective, multi-center, open-labeled, randomized trial of the efficacy of concurrent treatment with vitamin K2 and risedronate compared with risedronate alone and to explore subsets of patients for which concurrent treatment is particularly efficacious (trial identification number UMIN000000991). Inclusion criteria are women who meet the criteria for pharmacological therapy for osteoporosis, aged ≥65 years, have any of pre-specified risk factors, can walk unassisted, and are able to answer questionnaires. Exclusion criteria are prior warfarin use, secondary osteoporosis or non-osteoporotic metabolic bone diseases, contraindication for vitamin K2 and risedronate, hyper- or hypoparathyroidism, mental disorders, prevalent vertebral fracture at ≥6 sites, severe degenerative spinal deformation between T4 and L4, serious heart, liver, or kidney disease, or bisphosphonate use within the previous 6 months. Patients were recruited from 123 institutes between January 2008 and February 2010, and allocated to vitamin K2 (45 mg/day) and risedronate (2.5 mg/day or 17.5 mg/week) or risedronate alone (2.5 mg/day or 17.5 mg/week) groups. Primary endpoint is a vertebral or non-vertebral fracture. Secondary endpoints are bone mineral density, height, undercarboxylated osteocalcin, JOQOL, EQ-5D and safety. A sample size of 910 subjects per group and 2-year follow-up will provide 80 % power to detect 35 % risk reduction for fracture, with a two-sided significance level of 5 %. Subgroup analysis stratified to adjustment factors for random allocation, body mass index, 25-hydroxyvitamin D, estimated glomerular filtration rate, grade of vertebral fracture, JOQOL, EQ-5D, and co-morbidity is pre-specified.
鉴于双膦酸盐可能会干扰维生素K的激活，同时使用双膦酸盐和维生素K进行治疗很有前景。这是一项前瞻性、多中心、开放标签的随机试验，旨在比较维生素K2与利塞膦酸钠联合治疗与单独使用利塞膦酸钠的疗效，并探索联合治疗特别有效的患者亚组（试验识别号UMIN000000991）。纳入标准为符合骨质疏松症药物治疗标准的女性，年龄≥65岁，有任何预先指定的风险因素，能够独立行走，并且能够回答问卷。排除标准为既往使用过华法林、继发性骨质疏松症或非骨质疏松性代谢性骨病、维生素K2和利塞膦酸钠的禁忌症、甲状旁腺功能亢进或减退、精神障碍、≥6处椎体骨折、T4至L4之间严重的退行性脊柱畸形、严重的心、肝或肾病，或在过去6个月内使用过双膦酸盐。2008年1月至2010年2月期间，从123个机构招募患者，并将其分配到维生素K2（45毫克/天）和利塞膦酸钠（2.5毫克/天或17.5毫克/周）组或单独使用利塞膦酸钠（2.5毫克/天或17.5毫克/周）组。主要终点是椎体或非椎体骨折。次要终点是骨矿物质密度、身高、未羧化骨钙素、日本骨科学会生活质量（JOQOL）、欧洲五维度健康量表（EQ-5D）和安全性。每组910名受试者的样本量和2年的随访将提供80%的检验效能，以检测骨折风险降低35%，双侧显著性水平为5%。预先指定了根据随机分配的调整因素、体重指数、25-羟基维生素D、估计肾小球滤过率、椎体骨折分级、JOQOL、EQ-5D和合并症进行分层的亚组分析。
