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.

Impact of Osteonecrosis of the Jaw on Osteoporosis Treatment in Japan: Results of a Questionnaire-Based Survey by the Adequate Treatment of Osteoporosis (A-TOP) Research Group

“…A total of 488 clinics in Japan have been registered with the A-TOP research group. The A-TOP research group has completed two PROBE studies known as JOINT (Japanese Osteoporosis Intervention Trial)-02 and JOINT-03 to evaluate combination treatments [15,16], and it is currently undertaking the JOINT-04 project. The A-TOP group has collected documentation for a total of 7500 patients with osteoporosis who have a high risk of fracture.…”

Warfarin and Vascular Calcification

“…21,22 Due to increasing evidence that vitamin K metabolism may play an important role in bone health, there is now an ongoing clinical trial to study the effect of supplementation of vitamin K in patients with osteoporosis. 23…”

Association between serum visfatin levels and psoriasis and their correlation with disease severity: a meta-analysis

“…They identified genes induced by vitamin K in an SXR-dependent manner, including Tsukiji (Tsk), matrlin-2 (Matn2), and CD14, through comprehensive transcriptome analysis using microarrays. 8 Several case reports and case series have described the benefits of using VK2 to prevent AFFs, including combined treatment 9 or prior administration of VK2. 10 However, no cases or studies have focused on the use of VK2 to treat patients with AFFs.…”