Comparison of concurrent treatment with vitamin K2 and risedronate compared with treatment with risedronate alone in patients with osteoporosis: Japanese Osteoporosis Intervention Trial-03

Abstract

The aim of this study was to investigate the efficacy of concurrent treatment with vitamin K and risedronate compared with treatment with risedronate alone in patients with osteoporosis and to explore subsets of patients for which concurrent treatment is particularly efficacious. Women with osteoporosis aged 65 years or older were recruited from 123 institutes in Japan and allocated to take either vitamin K (45 mg/day) and risedronate (2.5 mg/day or 17.5 mg/week) or risedronate (2.5 mg/day or 17.5 mg/week) alone. The primary end point was the incidence of any fracture (vertebral and nonvertebral). The secondary end points were bone mineral density, height, undercarboxylated osteocalcin concentration, quality of life, and safety. Over a 2-year follow-up, vertebral or nonvertebral fractures occurred in 117 or 22 sites respectively among 931 patients in the risedronate and vitamin K group and in 104 or 26 sites respectively among 943 patients in the risedronate alone group. The rates of any incident fracture were similar between the two groups (incidence rate ratio 1.074, 95 % confidence interval 0.811-1.422, p = 0.62), implying that the primary end point was not met. There were no differences in the degree of increase in bone mineral density between the two groups. Undercarboxylated osteocalcin concentration decreased from 5.81 ± 3.93 ng/mL to 2.59 ± 1.52 ng/mL at 6 months in the risedronate and vitamin K group, whereas the change in the risedronate alone group was minimal (from 5.96 ± 4.36 ng/mL to 4.05 ± 3.40 ng/mL at 6 months) (p < 0.01). The treatment discontinuation rate was higher in the risedronate and vitamin K group than in the risedronate alone group (10.0 % vs 6.7 %). No unknown adverse drug reactions were reported. In conclusion, concurrent treatment with vitamin K and risedronate was not efficacious compared with monotherapy with risedronate in terms of fracture prevention.

Nutrients in the Prevention of Osteoporosis in Patients with Inflammatory Bowel Diseases

“…The study, conducted among postmenopausal Japanese women with osteoporosis, indicated that the administration of risedronic acid with vitamin K (45 g/day) was not more beneficial than administration without vitamin K supplementation. In fact, there was no statistically significant difference in fractures within the studied group [ 86 ]. Another study demonstrated that supplementation of menaquinone decreased carboxylated osteocalcin to a undercarboxylated osteocalcin ratio in young adults (47 ± 14 years old) and in postmenopausal women [ 87 ].…”

Role of Vitamin K in Bone and Muscle Metabolism

“…The results of these studies are mixed. Whilst some found a significant reduction in fracture risk [61,77,89], others did not [80,90]. A first meta-analysis of osteopenic/ osteoporotic patients and controls showed reduction of fracture risk in patients, but not in controls [77].…”

Vitamin K as a Powerful Micronutrient in Aging and Age-Related Diseases: Pros and Cons from Clinical Studies

“…In both groups, the incidence of fractures, changes in BMD, height and ucOC concentration, was evaluated over a 2-year follow-up. The authors concluded that, in terms of fracture prevention, there was no difference between both treatments [55]. Also, given the variability of vitamin K2 supplementation doses included in the different studies, and the different conclusions, it is reasonable to suggest that different formulations of vitamin K appear to have different levels of potency, and that higher doses might be necessary to fully carboxylate OC.…”