In this study, supplementation with vitamins K and D, and with calcium for 6 months of treatment significantly improved the L3 BMD compared to supplementation with vitamin D and calcium in postmenopausal Korean women over sixty years old. In addition, femur BMD was increased in the vitamin K group (vitamin K + vitamin D + calcium), but a similar increase was observed in the control group (vitamin D + calcium supplementation). The UcOC concentration significantly decreased in the vitamin K group compared to the control group (P < 0.01), and the osteocalcin level increased nonsignificantly in the vitamin K group (P = 0.14). The triglyceride level decreased in the vitamin K group, but was not statistically different from the control group. Similar results were observed in the ITT analysis.
When vitamin K concentration in the body is low, insufficient amount of osteocalcin completes γ-carboxylation; consequently, UcOC concentration increases and the affinity to calcium to bone matrix decreases. Gla-residues of osteocalcin combine with calcium and require vitamin K to activate the reaction site. Therefore, measuring UcOC concentration is a more accurate method of monitoring vitamin K than prothrombin in the liver (19
In a previous cross-sectional study in postmenopausal women, elevated serum UcOC and low spinal BMD were observed in the low plasma phylloquinone (vitamin K1
) group (20
). In another study, healthy elderly Scottish women who took vitamin K1
with vitamin D and calcium showed a sustained increase in BMD at the site of the ultradistal radius in comparison with women taking calcium and vitamin D (21
). A combined vitamin K2
therapy with vitamin D3
for postmenopausal Japanese women produced low serum UcOC and improved BMD values (22
). In an examination of the effects of vitamin K2
(45 mg/day) supplementation with calcium (1,500 mg/day) on lumbar BMD in postmenopausal women in Indonesia, a meaningful increase in BMD and a decrease in UcOC level were reported (18
). On the other hand, a study reported no vitamin K effect on BMD in North American women, prompting the suggestion that women receiving calcium and vitamin D supplements do not need additional vitamin K supplementation to prevent osteoporosis (23
). Another recent study of vitamin K1
supplementation for 2-4 yr in Canadian women also reported no benefits on age-related decline in BMD (12
). Our study showed that compared to the control group that took vitamin D and calcium, additional vitamin K supplementation to vitamin D and calcium improved L3 BMD in Korean postmenopausal women over sixty. Our previous cross-sectional study involving Korean women reported an inverse association between UcOC and BMD (6
). This dichotomy may partially be due to an ethnic difference and subjects' age in the bone metabolism or response to vitamin K or UcOC. A study of inflammatory bowel disease patients in Japanese women reported a decrease in the concentrations of vitamin K and D, and a resulting decrease in BMD (24
). The foregoing results imply that ethnic-related diversity in gastrointestinal absorption may explain the different response to vitamin K supplement and its subsequent effects on BMD (25
Several studies reported that obesity has been related to the level of vitamin K in adipose tissue, reflecting it's fat-soluble nature. In one study, obese patients displayed a lower UcOC concentration and their UcOC/osteocalcin ratio was negatively related with body mass index (26
). Another study reported that people with a high serum triglyceride level had high BMD in skeletal muscles (27
). On the other hand, adult obesity has been inversely related to circulating indicators of serum vitamin K (28
Limitations of the study were the small number of participants, relatively high dropout rate, and lack of a placebo group (i.e., no supplementation). The dosages of vitamin K, vitamin D and calcium and the duration of treatment may have been insufficient to induce responses in related biochemical markers and total BMD. Moreover, we did not measure and compare the dietary vitamin K intake. Also, bone quality was not measured, which might be only a minor limitation. A previous study (6
) suggested that UcOC concentration is inversely associated with age, with higher UcOC concentrations in younger women. This suggests that the effect of the vitamin K on osteocalcin may also be age-related. Given the advanced age of our study subjects (mean age 68 yr) and relatively short treatment period, the study may have not been able to discern an increase all part of BMD. However, it is noteworthy that changes in UcOC concentration among older women have been reported, with UcOC concentration in women in their 50 sec being higher than that in women in their 60 sec and 70 sec (6
). Therefore, vitamin K may be more effective in preventing bone loss or improving BMD in women aged 50-59 yr, especially in perimenopausal women or women with few years of menopause. A study testing the influence of vitamin K supplementation to perimenopausal women or women with few years of menopause for more than 6 months is needed. In addition, inconsistent findings from different countries suggest that a comparison of Korean data with data from other countries is warranted. A study design involving a longer duration of vitamin K supplementation and with postmenopausal women having a short duration of menopause may prove valuable. Finally, physical activity was not measured.
In conclusion, in this randomized study, supplementation with vitamin K, D and calcium for 6 months improves L3 BMD and reduces UcOC concentration in Korean postmenopausal women over sixty.