Table 3. Changes in BMD and biochemical markers from the baseline to 6 months Vitamin K + D Vitamin D + Ca Variables P value + Ca (n = 18) (n = 27) SBP (mm/Hg) 0.5 ± 3.1 1.2 ± 6.1 0.832 DBP (mm/Hg) 11.0 ± 13.1 5.6 ± 4.6 0.480 BMD (g/cm2) Lumbar 1 -0.0009 ± 0.04 0.009 ± 0.04 0.377 Lumbar 2 -0.01 ± 0.04 -0.0048 ± 0.03 0.618 Lumbar 3 0.01 ± 0.03 -0.008 ± 0.04 0.049 Lumbar 4 0.007 ± 0.05 0.005 ± 0.04 0.888 BMD femur neck (g/cm2) 0.01 ± 0.031 0.01 ± 0.027 0.890 BMD femur ward (g/cm2) 0.06 ± 0.10 0.03 ± 0.07 0.269 Total cholesterol (mg/dL) -6.1 ± 42.8 10.6 ± 29.2 0.169 Triglyceride (mg/dL) -10.0 ± 59.1 10.5 ± 78.7 0.335 UcOC (ng/dL) -1.6 ± 1.6 -0.4 ± 1.1 0.008 Osteocalcin (ng/dL) 1.6 ± 5.8 -1.1 ± 6.0 0.136 BSALP (µg/liter) -2.1 ± 34.3 7.6 ± 41.0 0.390 BUN (mg/dL) -0.5 ± 3.6 0.0 ± 4.1 0.618 Creatinine (mg/dL) 0.02 ± 0.09 0.007 ± 0.08 0.566 HDL (mg/dL) 2.0 ± 9.4 3.0 ± 8.1 0.713 Calcium (mg/dL) 0.2 ± 0.3 0.1 ± 0.3 0.232 All values are mean ± standard deviation. P values from independent t test. D, vita- min D; Ca, calcium supplement; SBP, systolic blood pressure; DBP, diastolic blood pressure; BMD, bone mineral density; UcOC, undercarboxylated osteocalcin; BSALP, serum bone-specific alkaline phosphatase; BUN, blood urea nitrogen; HDL, high-den- sity lipoprotein. complained of nausea sensation twice after taking vitamin K. No other participants including people in the control group re- ported adverse events during the study period. In summary, after 6 months treatment of vitamin K to the post- menopausal women over sixty, the L3 BMD increased signifi- cantly compared to the control group. In addition, the changes in some biochemical markers differed by treatment. Compared to the control group, the vitamin K group significantly decreased serum UcOC concentration (P = 0.008). Osteocalcin level was higher in the vitamin K group than in the control group, but the difference was not significant (P = 0.14). DISCUSSION 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 calci- um in postmenopausal Korean women over sixty years old. In addition, femur BMD was increased in the vitamin K group (vi- tamin K + vitamin D + calcium), but a similar increase was ob- served in the control group (vitamin D + calcium supplementa- tion). 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 vita- min 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; consequent- 1096 http://jkms.org Je SH, et al. • Vitamin K Supplement and BMD, UcOC Changes ly, 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 wom- en, elevated serum UcOC and low spinal BMD were observed in the low plasma phylloquinone (vitamin K1) group (20). In an- other 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 wom- en 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) supple- mentation with calcium (1,500 mg/day) on lumbar BMD in post- menopausal 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 wom- en 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-re- lated 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 pre- vious cross-sectional study involving Korean women reported an inverse association between UcOC and BMD (6). This dichot- omy 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 re- sults imply that ethnic-related diversity in gastrointestinal ab- sorption may explain the different response to vitamin K sup- plement 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 na- ture. In one study, obese patients displayed a lower UcOC con- centration and their UcOC/osteocalcin ratio was negatively re- lated 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 cal- cium and the duration of treatment may have been insufficient DOI: 10.3346/jkms.2011.26.8.1093