Vitamin K Deficiency: Bone Health and Fractures

Table of Contents

1. What Low Vitamin K Does to Bone (and Why It Is Silent)
2. The Mechanism: Osteocalcin, the Calcium “Velcro”
3. K1 vs K2: Why the Form Matters for Bone
4. What the Fracture Evidence Actually Shows
5. Bone Loss Has Many Causes
6. When Low Vitamin K Is a Plausible Piece of the Puzzle
7. What Lowers Vitamin K Status
8. How Bone and Vitamin K Status Are Measured
9. What the Research Reports on Intake, Supplements and Safety
10. Signs of Fracture Described in the Guidelines
11. Key Research Papers
12. Connections
13. Featured Videos

What Low Vitamin K Does to Bone (and Why It Is Silent)

Osteoporosis itself is nearly asymptomatic; its consequence is fracture, which the 2011 Japanese osteoporosis guidelines describe as severely impairing quality of life, and those guidelines note that most prevalent fragility fractures are vertebral fractures, usually without pain (Orimo 2012). A low vitamin K status adds nothing that can be felt: its proposed effect on bone runs through osteocalcin carboxylation, which can only be seen in a blood test or a research measurement. (Other mineral shortfalls, such as low potassium or low calcium, are covered in the Minerals section.)

Osteoporotic fractures are also called fragility fractures (Orimo 2012). In the Japanese diagnostic criteria, the presence of a fragility fracture alone confirms the diagnosis of osteoporosis (Orimo 2012).

Low vitamin K is one contributor among several, not a stand-alone disease. The 2011 Japanese guidelines describe insufficient vitamin K intake as a fracture risk factor independent of bone density in elderly women and in patients with osteoporosis treated with a bisphosphonate (Orimo 2012); the section on other causes of bone loss below sets out the rest.

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The Mechanism: Osteocalcin, the Calcium “Velcro”

Osteocalcin is made by osteoblasts (bone-building cells) and is either deposited into bone or released into the circulation, where its level correlates with histological measures of bone formation (Gundberg 2012). It regulates the size and shape of hydroxyapatite, the mineral of bone, through its vitamin K-dependent, gamma-carboxylated form (Booth 2013).

The chemistry, in plain terms: osteocalcin and the other members of the Gla-protein family need vitamin K for their synthesis (Vermeer 2012). Vitamin K allows gamma-carboxylation of glutamyl residues, a conversion that activates clotting factors and bone proteins, and vitamin K antagonists such as warfarin inhibit this process (Gage 2006). Osteocalcin that is not fully carboxylated is called undercarboxylated osteocalcin (ucOC).

An analogy. Osteocalcin can be pictured as strips of Velcro and vitamin K as the machine that stamps the hooks onto them: with enough vitamin K the strips carry their three Gla “hooks”; with too little, more strips leave the factory without them. The analogy is only a picture of the chemistry; how osteocalcin works in living bone has not been fully worked out (Gundberg 2012).

In humans, the percentage of circulating osteocalcin that is not carboxylated (percent ucOC) is used as a biomarker of vitamin K status; when ucOC is not corrected for total osteocalcin, it is confounded by bone-formation activity independent of vitamin K (Gundberg 2012). In 195 elderly institutionalized French women, the 15 who went on to fracture a hip over 18 months had higher baseline ucOC, and ucOC also tracked poor vitamin D status (Szulc 1993). In the larger EPIDOS cohort of independently living women over 75, ucOC in the highest quartile predicted hip fracture (odds ratio 1.9; 95% CI 1.2–3.0), and still did after adjustment for femoral-neck bone density and gait speed (1.8; 1.0–3.0) (Vergnaud 1997). Observational studies using percent ucOC led to the conclusion that vitamin K insufficiency leads to age-related bone loss, but clinical trials do not provide overall support for the suggestion that vitamin K supplementation of the general population will reduce bone loss or fracture risk (Gundberg 2012).

Vitamin K also activates matrix Gla protein, which has a key function in inhibiting arterial calcification (Vermeer 2012); that topic is covered on the vitamin K and arterial calcification page. For the bone story, osteocalcin is the protein that matters most.

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K1 vs K2: Why the Form Matters for Bone

Vitamin K is not a single molecule. There are two main families:

• Vitamin K1 (phylloquinone) — the most abundant form of vitamin K in US diets, with green vegetables the predominant dietary source (Harshman 2017); examples include kale, spinach, collards and broccoli.
• Vitamin K2 (menaquinones, abbreviated MK-n) — a family that differs in side-chain length and is synthesized by intestinal bacteria (Palermo 2017). Natto, a Japanese fermented soybean food, is the MK-7 source studied in Japan, and in Europe and North America cheese and curd cheese are described as the richest K2 sources (Vermeer 2012; see natto). The two most-studied members are MK-4 and MK-7.

Why the difference may matter for the skeleton: in one review's account, most vitamin K1 is retained by the liver for clotting-factor synthesis, whereas K2 is carried in low-density lipoproteins and released into the bloodstream, supplying tissues outside the liver, including bone and arteries (Vermeer 2012). In healthy volunteers, MK-7 had a very long half-life, giving much more stable serum levels than K1 and 7- to 8-fold higher levels during prolonged intake (Schurgers 2007); Knapen and colleagues give its circulating half-life as 3 days, against 1–2 hours for MK-4 (Knapen 2007). All 7 trials with fracture data in a 2006 meta-analysis were Japanese and used menaquinone (Cockayne 2006). The differences between the two K2 forms are explored further on the MK-7 vs MK-4 page.

The same review reports that hepatic vitamin K insufficiency has never been reported in healthy adults and that the clotting factors are fully carboxylated in the normal adult population, whereas in non-supplemented adults 20–30% of osteocalcin and matrix Gla protein occurs in the non-carboxylated state (Vermeer 2012). That contrast is why a normal clotting test says little about the vitamin K supply to bone. Measuring K2 directly is difficult: menaquinones are generally not detected in the circulation unless large quantities are consumed (Shea & Booth 2016).

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What the Fracture Evidence Actually Shows

The evidence linking vitamin K to bone comes in a few layers, and they do not all point with the same strength.

Observational studies (low intake linked to more hip fractures). In the Nurses' Health Study (72,327 women aged 38–63, 10 years of follow-up, 270 hip fractures), women in quintiles 2–5 of vitamin K intake had a lower age-adjusted relative risk of hip fracture (RR 0.70; 95% CI 0.53–0.93) than women in the lowest quintile (below 109 micrograms a day); risk did not decrease further between quintiles 2 and 5, and women eating lettuce, the largest contributor to their vitamin K intake, one or more times a day had a lower risk than those eating it once a week or less (RR 0.55; 0.40–0.78) (Feskanich 1999). In the Framingham Heart Study (335 men and 553 women, average age 75), people in the highest quartile of vitamin K intake (median 254 micrograms a day) had a lower fully adjusted relative risk of hip fracture (RR 0.35; 0.13–0.94) than those in the lowest quartile (median 56 micrograms a day) (Booth 2000). These are associations: they do not show that vitamin K caused the difference.

The bone-density question. In that Framingham cohort, vitamin K intake was not associated with bone mineral density in either men or women (Booth 2000). A later cross-sectional Framingham analysis of 1,112 men and 1,479 women did find lower femoral-neck and spine density in women in the lowest quartile of intake, but no association in men (Booth 2003). In trials, MK-4 at 45 mg a day did not change DXA bone density in Dutch postmenopausal women but increased bone mineral content and femoral-neck width, and hip bone strength was maintained while it fell with placebo (Knapen 2007). The Japanese guidelines state that bone density accounts for almost 70% of bone strength and bone quality for the remaining 30%, and that menatetrenone is considered to reduce fractures by a mechanism other than increasing bone density (Orimo 2012).

Randomized trials (the harder test). Trials that actually give people vitamin K are mixed. In an open-label Japanese trial, 241 osteoporotic patients received MK-4 (menatetrenone) 45 mg a day or no treatment for two years: clinical fractures were more frequent in the untreated group, and lumbar bone density changed by −0.5% with treatment against −3.3% without (Shiraki 2000). The largest menatetrenone trial, the multicentre Japanese OF study, randomized osteoporotic postmenopausal women aged 50 or older to calcium alone (2,193 women) or calcium plus menatetrenone (2,185 women): new vertebral fractures over 36 months, the primary endpoint, did not differ significantly, and the lower 48-month rate of new clinical fractures with menatetrenone was not significant; a lower risk was seen in women with at least five vertebral fractures at baseline (Inoue 2009). A three-year trial of MK-7 (180 µg a day) in 244 healthy postmenopausal women decreased the age-related decline in bone mineral content and density at the lumbar spine and femoral neck, but not at the total hip, and bone strength was favourably affected (Knapen 2013). In the ECKO trial, 440 postmenopausal women with osteopenia took 5 mg a day of vitamin K1 or placebo for 2 to 4 years: bone density, the primary outcome, did not differ; fewer women in the vitamin K group had clinical fractures (9 versus 20), but the study was not powered to examine fractures and their numbers were small (Cheung 2008).

Meta-analyses, and the problem papers. Cockayne and colleagues (2006) pooled the 7 trials that reported fracture data — all Japanese, all using menaquinone — and reported large reductions in vertebral, hip and nonvertebral fractures. In 2018 the journal published a notice that the conclusions were based on data from trials since indicated as problematic or retracted: 3 of the 7 articles with fracture data came from a single centre whose trial data have since been found to be problematic or retracted, and readers were asked to take into account only the sensitivity analysis that excluded them (notice PubMed PMID: 29582046; Torgerson 2018). The original pooled seven-trial odds ratios are therefore not repeated here. The same group's 2019 update (36 studies of oral vitamin K), written after the integrity of some of the earlier evidence had been questioned, found no difference in vertebral fractures (OR 0.96; 0.83–1.11) and lower odds of any clinical fracture (OR 0.72; 0.55–0.95), which became 0.76 (0.58–1.01) when restricted to trials at low risk of bias. Its conclusion: for postmenopausal or osteoporotic patients there is no evidence that vitamin K affects bone mineral density or vertebral fractures, and it may reduce clinical fractures but the evidence is insufficient to confirm this (Mott 2019). Following concerns raised about the integrity of the Yamaguchi Osteoporosis Prevention Study (YOPS; Avenell 2020), a 2020 correction adjusted every meta-analysis estimate that had included it (Mott 2020 correction), and the YOPS report itself was retracted in 2025 (Ishida 2004; notice PubMed PMID: 40222753). Other vitamin K2 bone papers from one Japanese author group have also been retracted: two menatetrenone fracture trials in elderly patients with Alzheimer's disease (Sato 2005, Bone, retracted 2018; Sato 2011, Kurume Medical Journal, retracted because of scientific misconduct) and two reviews of vitamin K2 or menatetrenone for osteoporosis (Iwamoto 2004, retracted 2021; Iwamoto 2013, retracted 2019). None of these retracted papers is relied on here; they are listed, with their notices, in the Key Research Papers.

Where that leaves the evidence. Low vitamin K intake and high ucOC are associated with hip fracture, and there is a well-described mechanism (osteocalcin carboxylation). In Japan, menatetrenone at 45 mg a day is listed among the anti-osteoporotic prescriptions covered by public health insurance (launched in 1995), and the 2011 guidelines grade it B for bone density, vertebral and non-vertebral fractures and C for hip fracture; their summary of its fracture effect cites the 2006 Cockayne meta-analysis (Orimo 2012), which now carries the notice above. The largest menatetrenone trial found no overall reduction in new vertebral fractures (Inoue 2009), and the 2019 review judged the evidence on clinical fractures insufficient (Mott 2019). Calcium, vitamin D, protein and exercise are covered on the calcium and related pages.

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Bone Loss Has Many Causes

Osteoporosis and fragility fractures are multifactorial. The factors named in the 2011 Japanese osteoporosis guidelines include:

• Estrogen loss at menopause — low bone density is caused by activation of osteoclasts due to the estrogen deficiency associated with menopause (Orimo 2012).
• Aging itself — when bone resorption increases with age and menopause and exceeds bone formation, bone density begins to fall; inadequate secondary mineralization, microarchitecture deterioration and a decreased capacity for absorbing calcium with age also contribute (Orimo 2012).
• Low calcium intake — a poor intake of calcium increases fracture risk via low bone density (Orimo 2012). In elderly French women, ucOC also tracked poor vitamin D status (Szulc 1993). (See hypocalcemia and bone loss.)
• Glucocorticoid (steroid) medication, rheumatoid arthritis and secondary osteoporosis — listed as risk factors in the FRAX tool the guidelines adopted (Orimo 2012).
• Age, a previous fracture, a family history of fractures, smoking and drinking — risk factors independent of bone density; low body weight is a density-independent risk factor for hip fracture (Orimo 2012).
• Other medical causes — in elderly Medicare patients with atrial fibrillation, increasing age, high fall risk, hyperthyroidism, neuropsychiatric disease and alcoholism were independent predictors of osteoporotic fracture (Gage 2006).

Vitamin K belongs on that list: the same guidelines describe insufficient vitamin K intake as a fracture risk factor independent of bone density in elderly women and in patients with osteoporosis treated with a bisphosphonate (Orimo 2012). A fracture on its own does not show that vitamin K was low.

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When Low Vitamin K Is a Plausible Piece of the Puzzle

Situations in which the research points to a lower vitamin K status include:

• Impaired intestinal absorption. Crohn's disease and cystic fibrosis are among the chronic diseases reported to be associated with poor vitamin K status (Vermeer 2012).
• Low intake. In US adults (NHANES 2011–2012), 43.0% of men and 62.5% of women met the Adequate Intake for phylloquinone, with the lowest intakes among older men (Harshman 2017).
• Concurrent low vitamin D or calcium. In elderly French women, ucOC was negatively correlated with vitamin D (25OHD) and fell during a year of calcium and vitamin D2 treatment, which the authors read as showing that the rise in ucOC in the elderly reflects poor vitamin D status as well as some degree of vitamin K deficiency (Szulc 1993).
• Documented high undercarboxylated osteocalcin. The Japanese guidelines describe ucOC as usable as an index of vitamin K deficiency in bone (Orimo 2012).

For the other ways low vitamin K shows up, see the sibling pages on bleeding and easy bruising and newborn bleeding (VKDB); vitamin K deficiency is described as an acute, life-threatening condition due to excessive bleeding (Vermeer 2012).

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What Lowers Vitamin K Status

Hepatic vitamin K insufficiency has not been reported in healthy adults, while partial undercarboxylation of osteocalcin is common in non-supplemented adults (Vermeer 2012). Factors described in the research:

• Fat malabsorption — the K vitamins are fat-soluble (Vermeer 2012), and diseases that impair intestinal absorption, such as Crohn's disease and cystic fibrosis, have been reported to be associated with poor vitamin K status (Vermeer 2012).
• Low intake — fewer men than women in the US meet the Adequate Intake, with the lowest intakes among older men (Harshman 2017).
• Vitamin K antagonist anticoagulants (warfarin). Warfarin inhibits the gamma-carboxylation that activates both clotting factors and bone proteins (Gage 2006). Among 4,461 elderly Medicare patients with atrial fibrillation prescribed warfarin for a year or longer, the adjusted odds of osteoporotic fracture were 1.25 (1.06–1.48) compared with patients not prescribed it; the association was significant in men (OR 1.63) but not in women (OR 1.05), and use for less than a year was not associated with a significant increase (Gage 2006). A 2019 meta-analysis of 23 studies (22 observational, 1 randomized; 1,121,582 subjects) found no increase in the odds of fracture in vitamin K antagonist users versus controls (OR 1.01; 0.89–1.14), including among people using them for a year or longer (OR 1.07; 0.90–1.27), and a small increase among female users (OR 1.11; 1.02–1.21) and older users (Fiordellisi 2019). Extra vitamin K interferes with this medication (Vermeer 2012): preparations supplying 50 micrograms a day or more of MK-7 may interfere with oral anticoagulant treatment in a clinically relevant way (Schurgers 2007). The non-vitamin K antagonist oral anticoagulants do not act through vitamin K, and the same meta-analysis found no difference in fracture odds between vitamin K antagonist users and users of those drugs (OR 0.95; 0.78–1.15) (Fiordellisi 2019). Decisions about anticoagulants and vitamin K belong with the prescribing clinician.

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How Bone and Vitamin K Status Are Measured

There is no single biomarker that is considered a gold-standard measure of vitamin K status (Shea & Booth 2016). What is measured depends on the question:

• Clotting tests (PT/INR). The coagulation panel reflects the clotting factors made in the liver, which are fully carboxylated in the normal adult population even when part of the osteocalcin is not (Vermeer 2012); so a normal result does not describe the vitamin K supply to bone. It is relevant to the more severe deficiency that causes bleeding, covered on the bleeding page.
• Undercarboxylated osteocalcin (ucOC), or the percentage of osteocalcin that is undercarboxylated. Percent ucOC is used as a biomarker of vitamin K status; uncorrected ucOC also reflects bone-formation activity (Gundberg 2012). The undercarboxylated fractions of three vitamin K-dependent proteins can be measured in blood, change with supplementation and are only modestly correlated with each other (Shea & Booth 2016). The Japanese guidelines describe ucOC as usable as an index of vitamin K deficiency in bone (Orimo 2012).
• Bone mineral density (DEXA). The Japanese guidelines recommend measuring bone density of the lumbar spine and/or proximal femur by DXA, and spine radiography for vertebral fractures, which are usually painless (Orimo 2012).
• Supporting nutrients. ucOC tracked vitamin D status in elderly women (Szulc 1993), and calcium intake affects fracture risk through bone density (Orimo 2012). The vitamin D (25-OH) test and the calcium level on a comprehensive metabolic panel are described on their own pages.

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What the Research Reports on Intake, Supplements and Safety

• Food sources. Vegetables are the primary dietary source of phylloquinone (K1) in the US diet, with mixed dishes second (Harshman 2017); examples include kale, spinach, collards, Swiss chard and broccoli. Intestinal uptake of the K vitamins is substantially affected by the food matrix in which they are embedded (Vermeer 2012). For K2, natto is the MK-7 source studied in Japan, and cheese and curd cheese are described as the richest K2 sources in Europe and North America (Vermeer 2012). See the vitamin K food sources page for specifics.
• Adequate Intake (AI). The US Adequate Intake for phylloquinone is 120 µg/day for men and 90 µg/day for women; in NHANES 2011–2012, 43.0% of men and 62.5% of women met it (Harshman 2017). The 2011 Japanese osteoporosis guidelines give 250 to 300 µg of vitamin K a day (Orimo 2012).
• Doses used in the bone trials. The Japanese and Dutch MK-4 trials used 45 mg a day (Shiraki 2000; Knapen 2007). In the Dutch trial this was given as three 15 mg capsules spread over the day, because of MK-4's short 1–2 hour half-life, and the authors note that at this dose “the vitamin is used as a drug rather than as a food supplement” (Knapen 2007); the OF study used 15 mg menatetrenone capsules (Inoue 2009). The MK-7 bone trial used 180 µg a day (Knapen 2013), and the ECKO trial 5 mg a day of K1 (Cheung 2008).
• Warfarin and other vitamin K antagonists. Extra vitamin K interferes with these drugs (Vermeer 2012), and MK-7 at 50 µg a day or more may interfere with oral anticoagulant treatment in a clinically relevant way (Schurgers 2007). Decisions about supplements and anticoagulants belong with the clinician who manages the anticoagulation.
• Other bone factors. Calcium, vitamin D, exercise, smoking, alcohol and underlying conditions are covered on the calcium page and in the factors listed above (Orimo 2012). The bone biology of K2 is covered on the vitamin K2 and bone health page.

Safety findings. In ECKO, there were no significant differences in adverse effects between 5 mg a day of vitamin K1 and placebo over 2 to 4 years (Cheung 2008). In the OF study, adverse events and adverse reactions were more frequent with calcium plus menatetrenone than with calcium alone (Inoue 2009). One review reports that in thousands of subjects taking high doses of vitamin K for several years at the author's institute, no increased tendency to thrombosis was found, with the exception that vitamin K interferes with vitamin K antagonist anticoagulants (Vermeer 2012).

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Signs of Fracture Described in the Guidelines

Because vitamin-K-related bone change is silent, the signs that matter are those of a fracture or significant bone loss, whatever the cause. The 2011 Japanese osteoporosis guidelines describe:

• Vertebral fractures that cause no pain. Most prevalent fragility fractures are vertebral fractures, usually without pain, which is why spine radiography is used to find them; lower back pain and a rounded back are among the presentations radiography is used to assess (Orimo 2012).
• Loss of height. A loss of height of 4 cm or more relative to height at age 25 is named as a particularly important risk factor for osteoporotic fracture, and a rounded back is one of the physical findings that strongly suggest osteoporosis (Orimo 2012).
• A fragility fracture. In the Japanese diagnostic criteria, a fragility fracture alone confirms the diagnosis of osteoporosis (Orimo 2012).
• Hip fracture. Proximal femoral (hip) fractures directly lead to decreases in the activities of daily living and can leave patients bedridden, with a poor prognosis (Orimo 2012).
• Bleeding signs. The clotting side of vitamin K deficiency shows up as bleeding (Vermeer 2012); it is covered on the bleeding and easy bruising page.

None of these shows a vitamin K problem on its own; they are signs of a bone (or bleeding) problem with many possible causes, of which vitamin K is one. Questions about bone health belong with a clinician.

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Key Research Papers

1. Cockayne S, Adamson J, Lanham-New S, Shearer MJ, Gilbody S, Torgerson DJ (2006). Vitamin K and the prevention of fractures: systematic review and meta-analysis of randomized controlled trials. Archives of Internal Medicine;166(12):1256-1261. — DOI: 10.1001/archinte.166.12.1256. — doi:10.1001/archinte.166.12.1256 — Expression of concern (JAMA Intern Med 2018: PubMed PMID: 29582046)
2. Mott A, Bradley T, Wright K, Cockayne ES, Shearer MJ, Adamson J, Lanham-New SA, Torgerson DJ (2019). Effect of vitamin K on bone mineral density and fractures in adults: an updated systematic review and meta-analysis of randomised controlled trials. Osteoporosis International 30(8): 1543–1559. — PubMed PMID: 31076817
3. Mott A, Bradley T, Wright K, Cockayne ES, Shearer MJ, Adamson J, Lanham-New SA, Torgerson DJ (2020). Correction to: Effect of vitamin K on bone mineral density and fractures in adults: an updated systematic review and meta-analysis of randomised controlled trials. Osteoporosis International 31(11): 2269–2270. — PubMed PMID: 32965511
4. Shiraki M, Shiraki Y, Aoki C, Miura M (2000). Vitamin K2 (menatetrenone) effectively prevents fractures and sustains lumbar bone mineral density in osteoporosis. Journal of Bone and Mineral Research;15(3):515-521. — DOI: 10.1359/jbmr.2000.15.3.515. — doi:10.1359/jbmr.2000.15.3.515
5. Knapen MHJ, Drummen NE, Smit E, Vermeer C, Theuwissen E (2013). Three-year low-dose menaquinone-7 supplementation helps decrease bone loss in healthy postmenopausal women. Osteoporosis International;24(9):2499-2507. — DOI: 10.1007/s00198-013-2325-6. — doi:10.1007/s00198-013-2325-6
6. Feskanich D, Weber P, Willett WC, Rockett H, Booth SL, Colditz GA (1999). Vitamin K intake and hip fractures in women: a prospective study. The American Journal of Clinical Nutrition;69(1):74-79. — DOI: 10.1093/ajcn/69.1.74. — doi:10.1093/ajcn/69.1.74
7. Booth SL, Tucker KL, Chen H, et al. (2000). Dietary vitamin K intakes are associated with hip fracture but not with bone mineral density in elderly men and women. The American Journal of Clinical Nutrition;71(5):1201-1208. — DOI: 10.1093/ajcn/71.5.1201. — doi:10.1093/ajcn/71.5.1201
8. Booth SL, Broe KE, Gagnon DR, et al. (2003). Vitamin K intake and bone mineral density in women and men. The American Journal of Clinical Nutrition;77(2):512-516. — DOI: 10.1093/ajcn/77.2.512. — doi:10.1093/ajcn/77.2.512
9. Booth SL, Centi A, Smith SR, Gundberg C (2013). The role of osteocalcin in human glucose metabolism: marker or mediator? Nature Reviews Endocrinology;9(1):43-55. — PubMed PMID: 23147574
10. Szulc P, Chapuy MC, Meunier PJ, Delmas PD (1993). Serum undercarboxylated osteocalcin is a marker of the risk of hip fracture in elderly women. Journal of Clinical Investigation;91(4):1769-1774. — PubMed PMID: 8473517
11. Vermeer C (2012). Vitamin K: the effect on health beyond coagulation — an overview. Food & Nutrition Research;56:5329. — PubMed PMID: 22489224
12. Palermo A, Tuccinardi D, D'Onofrio L, et al. (2017). Vitamin K and osteoporosis: myth or reality? Metabolism;70:57-71. — PubMed PMID: 28403946
13. Holick MF (2007). Vitamin D deficiency. New England Journal of Medicine;357(3):266-281. — DOI: 10.1056/NEJMra070553. — doi:10.1056/NEJMra070553
14. Torgerson DJ (2018). Caution to readers about systematic review on vitamin K and prevention of fractures that included problematic trials. JAMA Internal Medicine 178(6): 863–864. — PubMed PMID: 29582044
15. Inoue T, Fujita T, Kishimoto H, Makino T, Nakamura T, Nakamura T, Sato T, Yamazaki K (2009). Randomized controlled study on the prevention of osteoporotic fractures (OF study): a phase IV clinical study of 15-mg menatetrenone capsules. Journal of Bone and Mineral Metabolism 27(1): 66–75. — PubMed PMID: 19082528
16. Knapen MH, Schurgers LJ, Vermeer C (2007). Vitamin K2 supplementation improves hip bone geometry and bone strength indices in postmenopausal women. Osteoporosis International 18(7): 963–972. — PubMed PMID: 17287908
17. Cheung AM, Tile L, Lee Y, Tomlinson G, Hawker G, Scher J, Hu H, Vieth R, Thompson L, Jamal S, Josse R (2008). Vitamin K supplementation in postmenopausal women with osteopenia (ECKO trial): a randomized controlled trial. PLoS Medicine 5(10): e196. — PubMed PMID: 18922041
18. Orimo H, Nakamura T, Hosoi T, Iki M, Uenishi K, Endo N, Ohta H, Shiraki M, Sugimoto T, Suzuki T, Soen S, Nishizawa Y, Hagino H, Fukunaga M, Fujiwara S (2012). Japanese 2011 guidelines for prevention and treatment of osteoporosis — executive summary. Archives of Osteoporosis 7(1): 3–20. — PubMed PMID: 23203733
19. Gundberg CM, Lian JB, Booth SL (2012). Vitamin K-dependent carboxylation of osteocalcin: friend or foe? Advances in Nutrition 3(2): 149–157. — PubMed PMID: 22516722
20. Vergnaud P, Garnero P, Meunier PJ, Bréart G, Kamihagi K, Delmas PD (1997). Undercarboxylated osteocalcin measured with a specific immunoassay predicts hip fracture in elderly women: the EPIDOS Study. Journal of Clinical Endocrinology and Metabolism 82(3): 719–724. — PubMed PMID: 9062471
21. Shea MK, Booth SL (2016). Concepts and controversies in evaluating vitamin K status in population-based studies. Nutrients 8(1): 8. — PubMed PMID: 26729160
22. Schurgers LJ, Teunissen KJ, Hamulyák K, Knapen MH, Vik H, Vermeer C (2007). Vitamin K-containing dietary supplements: comparison of synthetic vitamin K1 and natto-derived menaquinone-7. Blood 109(8): 3279–3283. — PubMed PMID: 17158229
23. Harshman SG, Finnan EG, Barger KJ, Bailey RL, Haytowitz DB, Gilhooly CH, Booth SL (2017). Vegetables and mixed dishes are top contributors to phylloquinone intake in US adults: data from the 2011–2012 NHANES. Journal of Nutrition 147(7): 1308–1313. — PubMed PMID: 28566528
24. Gage BF, Birman-Deych E, Radford MJ, Nilasena DS, Binder EF (2006). Risk of osteoporotic fracture in elderly patients taking warfarin: results from the National Registry of Atrial Fibrillation 2. Archives of Internal Medicine 166(2): 241–246. — PubMed PMID: 16432096
25. Fiordellisi W, White K, Schweizer M (2019). A systematic review and meta-analysis of the association between vitamin K antagonist use and fracture. Journal of General Internal Medicine 34(2): 304–311. — PubMed PMID: 30511289
26. Avenell A, Grey A, Gamble GD, Bolland MJ (2020). Concerns about the integrity of the Yamaguchi Osteoporosis Prevention Study (YOPS) report, Am J Med. 2004;117:549-555. American Journal of Medicine 133(6): e311–e314. — PubMed PMID: 32532372
27. Ishida Y, Kawai S (2004). Comparative efficacy of hormone replacement therapy, etidronate, calcitonin, alfacalcidol, and vitamin K in postmenopausal women with osteoporosis: the Yamaguchi Osteoporosis Prevention Study. American Journal of Medicine 117(8): 549–555. — PubMed PMID: 15465502 — Retracted (retraction notice: PubMed PMID: 40222753)
28. Sato Y, Kanoko T, Satoh K, Iwamoto J (2005). Menatetrenone and vitamin D2 with calcium supplements prevent nonvertebral fracture in elderly women with Alzheimer's disease. Bone 36(1): 61–68. — PubMed PMID: 15664003 — Retracted (retraction notice: PubMed PMID: 29150013)
29. Sato Y, Honda Y, Umeno K, Hayashida N, Iwamoto J, Takeda T, Matsumoto H (2011). The prevention of hip fracture with menatetrenone and risedronate plus calcium supplementation in elderly patients with Alzheimer disease: a randomized controlled trial. Kurume Medical Journal 57(4): 117–124. — PubMed PMID: 21778673 — Retracted (retraction notice: PubMed PMID: 28408729)
30. Iwamoto J, Takeda T, Sato Y (2004). Effects of vitamin K2 on osteoporosis. Current Pharmaceutical Design 10(21): 2557–2576. — PubMed PMID: 15320745 — Retracted (retraction notice: PubMed PMID: 34264184)
31. Iwamoto J, Sato Y (2013). Menatetrenone for the treatment of osteoporosis. Expert Opinion on Pharmacotherapy 14(4): 449–458. — PubMed PMID: 23346882 — Retracted (retraction notice: PubMed PMID: 31437064)

PubMed Topic Searches

1. PubMed: Vitamin K2 (menaquinone), bone density, and fracture
2. PubMed: Undercarboxylated osteocalcin and hip fracture risk
3. PubMed: MK-7 and postmenopausal bone loss
4. PubMed: Warfarin, bone density, and fracture risk
5. PubMed: Phylloquinone/menaquinone and osteoporosis (meta-analyses)

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Connections

• All Vitamins
• Vitamin K Overview
• Vitamin K Deficiency: Bleeding & Easy Bruising
• Vitamin K Deficiency: Newborn Bleeding (VKDB)
• Vitamin K2 and Bone Health
• MK-7 vs MK-4
• Vitamin K2 and Arterial Calcification
• Vitamin K Food Sources
• Osteoporosis
• Calcium
• Hypocalcemia and Bone Loss
• Magnesium
• Vitamin D (25-OH) Test
• Comprehensive Metabolic Panel
• Coagulation Panel
• Natto
• Kale

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