Maximal dose-response of vitamin-K2 (menaquinone-4) on undercarboxylated osteocalcin in women with osteoporosis.

Abstract

Low concentrations of serum vitamin K accompany high concentrations of undercarboxylated osteocalcin (ucOC) and osteoporotic fractures. Although vitamin K2 (MK-4) is approved as a therapeutic agent for the treatment of osteoporosis in some countries, the dose-response is unknown. The objective of this study was to assess the improvement in carboxylation of osteocalcin (OC) in response to escalating doses of MK-4 supplementation. A nine-week, open-labeled, prospective cohort study was conducted in 29 postmenopausal women who suffered hip or vertebral compression fractures. Participants took low-dose MK-4 (0.5mg) for 3 weeks (until the second visit), then medium-dose MK-4 (5mg) for 3 weeks (until the third visit), then high-dose MK-4 (45mg) for 3 weeks. The mean±SD age of the participants was 69±9years. MK-4 dose (p<0.0001), but neither age nor other relevant medications (e.g. bisphosphonates) correlated with improvement in %ucOC. As compared to baseline concentrations (geometric mean±SD) of 16.8±2.4, 0.5mg supplementation halved %ucOC to 8.7±2.2 (p<0.0001) and the 5-mg dose halved %ucOC again (to 3.9±2.2; p=0.0002 compared to 0.5-mg dose). However, compared to 5mg/day, there was no additional benefit of 45mg/day (%ucOC 4.6; p=NS vs. 5-mg dose). MK-4 supplementation resulted in borderline increases in γ-carboxylated osteocalcin (glaOC; p=0.07). There were no major side effects of MK-4 supplementation. In postmenopausal women with osteoporotic fractures, supplementation with either 5 or 45mg/day of MK-4 reduces ucOC to concentrations typical of healthy, pre-menopausal women.