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

Single-center randomized, placebo-controlled trial in postmenopausal women with osteopenia in Toronto, Canada. The vitamin K1 arm randomized 217 women who were vitamin D replete, had baseline serum 25-OH vitamin D 75.8 (23.6) nmol/l, and were not using bone-active medications.

Vitamin K1 (phylloquinone) was given orally at 5 mg daily for 2 years, with extension of follow-up to 4 years for early enrollees. Participants also received calcium and vitamin D throughout the trial (approximately 1,500 mg calcium and 800 IU vitamin D per day).

Daily 5 mg vitamin K1 did not prevent age-related bone loss at the lumbar spine or total hip over 2 years. Lumbar spine BMD changed by -1.28% with vitamin K1 versus -1.22% with placebo (p = 0.84), and total hip BMD changed by -0.69% versus -0.88% (p = 0.51). Vitamin K1 markedly increased serum vitamin K1 and reduced undercarboxylated osteocalcin, but did not clearly reduce bone resorption. Clinical fractures were fewer in the vitamin K1 group (9 vs 20 at 2 years; HR 0.41, 95% CI 0.15 to 1.18, p = 0.08; HR 0.45, 95% CI 0.20 to 0.98, p = 0.04 at 4 years), and cancers were also fewer (3 vs 12; HR 0.25, 95% CI 0.07 to 0.89), but these findings were secondary and may be due to chance. Overall, the treatment was well tolerated and did not show a clear skeletal benefit.

The trial was not powered for fracture or cancer outcomes, so those apparent benefits are uncertain. The main bone density endpoints were negative over 2 to 4 years, and the study was limited to relatively healthy, vitamin D replete postmenopausal women from a single center, which may reduce generalizability.