Bone Quality in Children may be Compromised by Therapy With Vitamin K-Antagonists

PL Thomas and its partner NattoPharma would like to make known a new publication by Avgeri et al. (J Pediatr Hematol Oncol) link, about the association of long-term oral anticoagulant therapy (OAC) resulting in a remarkable reduction in bone mineral density and significant impairment in other bone health parameters.

"This study provides an interesting insight into the effect of blocking vitamin K activity in the body, with potential long term ramifications for bone health," said Vitamin K expert Leon J Schurgers, senior scientist from VitaK, at the Maastricht University in the Netherlands.

The major outcome of the study was that children undergoing long-term oral anticoagulant therapy presented higher levels of inactive osteocalcin, indicative of poor vitamin K status. Moreover, bone resorption markers were enhanced whereas bone formation markers and vitamin D levels were lower in comparison to the control group. Additionally, more than half of the examined children in the patients group showed signs of osteopenia, which means their bone mineral density was lower than normal.

Dr. Schurgers continued, "Previous research by our group and others looking at OAC therapy in patients showed a significant increase in arterial calcification. The inactivation of the vitamin K-dependent protein matrix Gla-protein leads to impaired protection against arterial calcification. However, also in the apparently healthy population, some 40% impaired matrix Gla-protein is present. This would explain the Rotterdam study, showing that high intake of vitamin K2 reduced cardiovascular disease by some 50%. Clearly, given the role vitamin K plays in bone and cardiovascular health, we recommend increasing vitamin K intake from food and dietary supplements for all people. Individuals on OAC treatment should consult with their physician."

Oral anticoagulants, which inhibit vitamin K recycling, thereby create vitamin K-deficiency. As a result, this will lead to impaired carboxylation of osteocalcin, a vitamin K-dependent bone protein. As osteocalcin is fully dependent upon vitamin K to function optimally, long-term deficiency may lead to reduced bone density and quality of bone.

Results from the Avgeri study confirm previous findings that bone mineral density was significantly lower in adult stroke patients using long-term warfarin treatment compared to untreated patients. In this study osteopenia was ascribed as an effect of warfarin-induced inhibition of vitamin K-dependent protein activity.(1)

Numerous studies investigated the association between the impairment of vitamin K-dependent protein and excessive calcium accumulation in soft tissues. It was shown that calcification occurs more readily in cases where vitamin K recycling is inhibited. Indeed, though anticoagulants are usually instituted to avoid life-threatening cardiac diseases, the development of arterial calcification arises more readily in patients receiving such treatment. In men and women submitted to the OAC treatment, a two-fold increase in arterial calcification was found as compared to patients not receiving vitamin K-antagonists(2) (3). This is important since the survival rate was found to be associated with the amount of calcium present within the vasculature. Results published by Shaw et al. showed that significant calcification makes one older than the chronological age indicates; while an older person with little or no calcification can deduct up to 10 years from his or her actual age.(4)

Several studies had previously suggested the strongly protective effect of vitamin K2 on vascular calcium deposition. The Rotterdam Study (Geleijnse et. al., 2004) (5) found high dietary intake of vitamin K2 contributing to heart health. Research conducted on a group of 4807 elderly men and women indicated that eating large quantities of natural vitamin K2 (the optimal dose was 45 µg per day) reduces the risk of both arterial calcification and cardiovascular mortality by 50%, with no side effects. Also the outcomes from a new study carried on by Beulens et al.(6) supported the hypothesis of crucial role played by vitamin K2 (menaquinones) in the prevention of heart diseases: research discovered that high intakes of K2 were associated with decreased coronary calcification (meaning healthy and flexible vasculature).

MenaQ7 is the only dietary supplement providing the natural menaquinone-7 extracted from Japanese dish natto which at the dose of 45 µg will not likely interfere with "thinning" medicines, and does not provoke any additional risk of clot formation inside blood vessels.

(1) Sato Y, Honda Y, Kunoh H, Oizumi K. Long-term oral anticoagulation reduces bone mass in patients with previous hemispheric infarction and nonrheumatic atrial fibrillation. Stroke. 1997;28(12):2390-4. link

(2) Schurgers LJ, Aebert H, Vermeer C, Bültmann B, Janzen J. Oral anticoagulant treatment: friend or foe in cardiovascular disease? Blood. 2004 15;104(10):3231-2. link

(3) Koos R, Mahnken AH, Mühlenbruch G, Brandenburg V, Pflueger B, Wildberger JE, Kühl HP. Relation of oral anticoagulation to cardiac valvular and coronary calcium assessed by multislice spiral computed tomography. Am J Cardiol. 2005;96(6):747-9. link

(4) Shaw LJ, Raggi P, Berman DS, Callister TQ. Coronary artery calcium as a measure of biologic age. Atherosclerosis. 2006;188(1):112-9 link

(5) Geleijnse JM., et al. Dietary Intake of Menaquinone Is Associated with a Reduced Risk of Coronary Heart Disease: The Rotterdam Study. Nutritional Epidemiology 2004; 134: 3100-3105. link

(6) Beulens, JW, et. al., High dietary menaquinone intake is associated with reduced coronary calcification. Atherosclerosis 2008 (10.1016/j.atherosclerosis.2008.07.010) link

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About MenaQ7
MenaQ7 provides Natural Vitamin K2 as an extract of natto, a fermented soy food from Japan. Natto is particularly rich in the highly bio-available form of vitamin K2, menaquinone-7 (MK-7). MenaQ7 is the best documented commercially available Natural Vitamin K2 with guaranteed actives and stability, clinical substantiation and international patents awarded and pending.
For more information on the health benefits of MenaQ7, please visit

About NattoPharma
NattoPharma, Norway is the exclusive international supplier of MenaQ7, the natural Vitamin K2. NattoPharma has entered into a multi-year research and development program to substantiate and discover the health benefits of natural vitamin K2 for applications in the exciting marketplace for functional food and health food supplements.
For more information, please visit our website

About PL Thomas
PL Thomas, a New Jersey-based ingredient supplier offers fifty years of innovation in securing reliable, high quality raw materials for the food/functional food and nutrition industries. PLT is a one-stop resource for application solutions, current industry information and technical service, and specializes in water-soluble gums and clinically-supported botanical extracts.

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