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)

Shiro Tanaka, Teruhiko Miyazaki, Yukari Uemura, Tatsuhiko Kuroda, Nobuaki Miyakawa, Toshitaka Nakamura, Masao Fukunaga, Yasuo Ohashi, Hiroaki Ohta, Satoshi Mori, Hiroshi Hagino, Takayuki Hosoi, Toshitsugu Sugimoto, Eiji Itoi, Hajime Orimo, Masataka Shiraki

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5 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)298-304
Number of pages7
JournalJournal of Bone and Mineral Metabolism
Volume32
Issue number3
DOIs
Publication statusPublished - 2014 May

Keywords

  • 25-hydroxyvitamin D
  • Bisphosphonate
  • Osteoporosis
  • Quality of life
  • Undercarboxylated osteocalcin

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine
  • Endocrinology

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    Tanaka, S., Miyazaki, T., Uemura, Y., Kuroda, T., Miyakawa, N., Nakamura, T., Fukunaga, M., Ohashi, Y., Ohta, H., Mori, S., Hagino, H., Hosoi, T., Sugimoto, T., Itoi, E., Orimo, H., & Shiraki, M. (2014). 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). Journal of Bone and Mineral Metabolism, 32(3), 298-304. https://doi.org/10.1007/s00774-013-0491-4