Vitamin K Supplementation in Postmenopausal Women with Osteopenia (ECKO Trial): A Randomized Controlled Trial

PLoS Medicine

Oct 2008

DOI: 10.1371/journal.pmed.0050196

Citations:236

Influential Citations:10

Interventional (Human) Studies

Enhanced Details

Methods

Single-center randomized, double-blind, placebo-controlled trial enrolling 440 postmenopausal women with osteopenia; mean age 59 (range 40-82); 88% European Canadian; baseline 25-hydroxyvitamin D ~77 nmol/L; design included a 2-year primary period with extension for earlier enrollees up to 4 years.

Intervention

Vitamin K1, 5 mg orally daily, for 2 years (extension up to 4 years for early enrollees); taken in the morning with food.

Results

BMD at the lumbar spine declined by 1.28% with vitamin K1 vs 1.22% with placebo (p=0.84); at the total hip declined by 0.69% vs 0.88% (p=0.51); no significant differences at other sites over 2–4 years. Vitamin K1 raised serum vitamin K1 about 10-fold; ucOC decreased; CTX (bone resorption) did not differ. Fractures occurred in 9 (vitamin K1) vs 20 (placebo) by 4 years (HR 0.45; p=0.04); cancers occurred in 3 vs 12 (HR 0.25; p=0.02). Vitamin K1 was well tolerated with no major adverse effects or QoL differences. Conclusion: Daily 5 mg vitamin K1 does not prevent age-related BMD loss but may reduce fracture and cancer incidence; more trials are needed to confirm.

Limitations

Not powered to examine fracture or cancer outcomes; extension phase had variable duration with small numbers at 3-4 years; morphometric vertebral fractures assessed by VFA (less precise than radiography); small cancer number; single-center; participants were vitamin D replete, which may limit generalizability.

Abstract

Background Vitamin K has been widely promoted as a supplement for decreasing bone loss in postmenopausal women, but the long-term benefits and potential harms are unknown. This study was conducted to determine whether daily high-dose vitamin K1 supplementation safely reduces bone loss, bone turnover, and fractures. Methods and Findings This single-center study was designed as a 2-y randomized, placebo-controlled, double-blind trial, extended for earlier participants for up to an additional 2 y because of interest in long-term safety and fractures. A total of 440 postmenopausal women with osteopenia were randomized to either 5 mg of vitamin K1 or placebo daily. Primary outcomes were changes in BMD at the lumbar spine and total hip at 2 y. Secondary outcomes included changes in BMD at other sites and other time points, bone turnover markers, height, fractures, adverse effects, and health-related quality of life. This study has a power of 90% to detect 3% differences in BMD between the two groups. The women in this study were vitamin D replete, with a mean serum 25-hydroxyvitamin D level of 77 nmol/l at baseline. Over 2 y, BMD decreased by −1.28% and −1.22% (p = 0.84) (difference of −0.06%; 95% confidence interval [CI] −0.67% to 0.54%) at the lumbar spine and −0.69% and −0.88% (p = 0.51) (difference of 0.19%; 95% CI −0.37% to 0.75%) at the total hip in the vitamin K and placebo groups, respectively. There were no significant differences in changes in BMD at any site between the two groups over the 2- to 4-y period. Daily vitamin K1 supplementation increased serum vitamin K1 levels by 10-fold, and decreased the percentage of undercarboxylated osteocalcin and total osteocalcin levels (bone formation marker). However, C-telopeptide levels (bone resorption marker) were not significantly different between the two groups. Fewer women in the vitamin K group had clinical fractures (nine versus 20, p = 0.04) and fewer had cancers (three versus 12, p = 0.02). Vitamin K supplements were well-tolerated over the 4-y period. There were no significant differences in adverse effects or health-related quality of life between the two groups. The study was not powered to examine fractures or cancers, and their numbers were small. Conclusions Daily 5 mg of vitamin K1 supplementation for 2 to 4 y does not protect against age-related decline in BMD, but may protect against fractures and cancers in postmenopausal women with osteopenia. More studies are needed to further examine the effect of vitamin K on fractures and cancers. Trial registration: ClinicalTrials.gov (#NCT00150969) and Current Controlled Trials (#ISRCTN61708241) show less