title: Design of a randomized clinical trial of concurrent treatment with vitamin K2 and risedronate compared to risedronate alone in osteoporotic patients: Japanese Osteoporosis Intervention Trial-03 (JOINT-03).
abstract: 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.
authors.affiliation: Department of Pharmacoepidemiology, Graduate School of Medicine and Public Health, Kyoto University, Kyoto, Japan, tanaka.shiro.8n@kyoto-u.ac.jp.
authors.forename: Shiro
authors.initials: S
authors.lastname: Tanaka
authors.forename: Teruhiko
authors.initials: T
authors.lastname: Miyazaki
authors.forename: Yukari
authors.initials: Y
authors.lastname: Uemura
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Kuroda
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Miyakawa
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Nakamura
authors.forename: Masao
authors.initials: M
authors.lastname: Fukunaga
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ohashi
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ohta
authors.forename: Satoshi
authors.initials: S
authors.lastname: Mori
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hagino
authors.forename: Takayuki
authors.initials: T
authors.lastname: Hosoi
authors.forename: Toshitsugu
authors.initials: T
authors.lastname: Sugimoto
authors.forename: Eiji
authors.initials: E
authors.lastname: Itoi
authors.forename: Hajime
authors.initials: H
authors.lastname: Orimo
authors.forename: Masataka
authors.initials: M
authors.lastname: Shiraki
mesh_terms: D000368:Aged; D015992:Body Mass Index; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D012968:Etidronic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D015675:Osteocalcin / Q000378:metabolism; D010024:Osteoporosis / Q000188:drug therapy* / Q000378:metabolism; D011446:Prospective Studies; D000068296:Risedronic Acid; D016103:Spinal Fractures / Q000188:drug therapy / Q000378:metabolism; D014807:Vitamin D / Q000031:analogs & derivatives / Q000378:metabolism; D024482:Vitamin K 2 / Q000627:therapeutic use*
chemical_list: D050071:Bone Density Conservation Agents; D015675:Osteocalcin; D024482:Vitamin K 2; D014807:Vitamin D; C104450:25-hydroxyvitamin D; D000068296:Risedronic Acid; D012968:Etidronic Acid