Table 3.
Interventional studies for the effect of vitamin K in bone mineral density and fractures since 2015
| Study, year [ref] | Population | N | Duration | Supplementation | ucOCN | Serum VK | VK measure method | BMD | BTM | Fracture risk | Other |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Huang et al., 2015 [77]* | Japanese or East Asian, mostly postmenopausal women with OP; Caucasian healthy postmenopausal women | 6759 | 6–48 months | 100 ug—45 mg/day MK-4 or MK-7, some with Ca (133.8 mg/day to 2 g/day) or vitamin D3 (0.75-10ug/day). 2 studies received bisphosphonates (17.5 mg/week risedronate or 5 mg/day alendronate) | Yes | – | – | Increased at LS. No changes in non-OP | Decreased ucOCN | Decrease. No changes in non-OP | – |
| Rønn et al., 2016 [78] | Postmenopausal Caucasian women with osteopenia | 142 | 12 months | 375ug MK-7, 800 mg calcium and 38ug vitD, daily | Yes | – | – | No difference | No change in P1NP or CTx; increased BSAP; decreased ucOCN after 3 months | – | Trabecular number did not change in VK but decreased in placebo; trabecular thickness unchanged in VK but increased in placebo |
| Ebina et al., 2016 [107] | Japanese men and postmenopausal women | 160 | 12 months | 50 mg/month minodronate and 45 mg/day VK2 or eldecalcitol 0.75ug/day | – | – | – | Increased | Decreased P1NP | – | – |
| Shikano et al., 2016 [108] | Japanese patients with glucocorticoid-induced osteoporosis | 60 | 4 weeks | 45 mg/day VK2 and 30–60 mg/day prednisolone | Yes | – | – | No difference | Increased P1NP, decreased ucOCN | No difference at 1.5 years | – |
| Kodama et al., 2017 [109] | Japanese adults with cerebral palsy and osteoporosis | 32 | 12 months | 45 mg VK2/day | Yes | – | – | Increased | Decreased ucOCN | – | – |
| Maria et al., 2017 [61] | Caucasian postmenopausal women with osteopenia | 20 | 12 months | 5 mg melatonin, 450 mg strontium (citrate), 2000 IU vitamin D3 and 60ug VK2 | – | – | – | Increased | Increased P1NP, reduced CTx:P1NP ratio | reduced for major OP fx | – |
| Tanaka et al., 2017 [80] | Japanese women over 65 years | 1983 | 2 years | 45 mg/day VK2 and 2.5 mg/day or 17.5 mg/week risedronate | Yes | – | – | No difference | Decreased ucOCN at 6 months | No difference | – |
| Barnuevo et al., 2018 [83] | Healthy Caucasian premenopausal women | 181 | 18 months | Dairy product supplemented with either 1ug of vit D or 1ug vitamin D and 18ug VK2 or nothing else | Yes | – | – | No difference | No difference | – | – |
| Su et al., 2019 [90] * | Japanese, Chinese and Indonesian (70% postmenopausal women) | 8882 | 2 weeks—4 years | 45–90 mg/day menatetrenone# | Yes | – | – | Increased | Decreased ucOC/OC | Non-significant decrease | Increase incidence of adverse effects and adverse drug reactions |
| Mott et al., 2019 [89]* | Postmenopausal women with or without OP; patients with cirrhosis; patients with chronic glomerular nephritis; healthy population; patient population. East Asian, Caucasian and Iranian populations | 11,112 | 6–48 months | 100ug-45 mg VK1 or VK2, 150 mg-3 g Ca/0.5-38ug Vit D. Some studies had corticosteroids or bisphosphonates | – | – | – | Increased. If only low risk of bias studies, no significant difference | – | Decreased in clinical fractures, no difference in vertebral fractures | – |
| Morato-Martinez et al., 2020 [82] | Postmenopausal Caucasian women with osteopenia | 78 | 24 weeks | Dairy preparation with or without calcium, vitD, VK, vit C, zinc, magnesium, L-leucine and probiotics | – | – | – | Increased | Increased P1NP, decreased CTx | – | |
| Bartstra et al., 2021 [110] | DM2 and CVD patients | 68 | 6 months | 360ug/day VK2 | – | – | – | No difference | – | – | No difference on dp-ucMGP |
| Rønn et al., 2021 [79] | Postmenopausal Caucasian women with osteopenia | 142 | 3 years | 375 ug/day MK-7, 38 ug vit D, 800 mg calcium | Yes | – | – | No difference | Increased cOCN; no difference in CTx, P1NP, BSAP, vit D | – | No changes in microstructure of bone |
| Torbergsen et al., 2019 [81] | Caucasian patients with hip fracture | 71 | 4 months | 150 ug VK1, 20 ug vitD and 1000 mg Ca, 250 ug vit A, 10 mg vit E, 1,2 g omega3 fatty acids | Yes | Yes | HPLC | – | Decrease CTx and ucOCN | – | VK1 increased after intervention (not significant when adjusted by baseline differences) |
| Zhang et al., 2020 [111] | Chinese men and postmenopausal women 50–75 years | 311 | 12 months | 50-90ug/day MK-7, 500 mg/day calcium and 10ug/day vit D3 | Yes | Yes | ELISA | Decrease in FN in women at 90ug (with and without ca/vitD), but no men | Increased cOCN/ucOCN ratio | – | VK2 increased after 12 months of intervention |
*Meta-analysis. #menatetrenone = synthetic form of VK-2, chemically similar to MK-4. ucOCN undercarboxylated OCN, BMD bone mineral density, BTM bone turnover biomarkers, OP osteoporosis, DM2 diabetes mellitus type 2, CVD cardiovascular disease, dp-ucMGP dephosphorylated-uncarboxylated MGP, CTX1 Type I collagen cross-linked C-telopeptide, BSAP bone specific alkaline phosphatase, P1NP total procollagen type I N-terminal propeptide, cOCN carboxylated OCN