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01-05-2014 | Original Article

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)

Authors: 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

Published in: Journal of Bone and Mineral Metabolism | Issue 3/2014

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.

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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)
Authors: 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
Publication date: 01-05-2014
Publisher: Springer Japan
Published in: Journal of Bone and Mineral Metabolism / Issue 3/2014
Print ISSN: 0914-8779
Electronic ISSN: 1435-5604
DOI: https://doi.org/10.1007/s00774-013-0491-4

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