They found children who took anticoagulants long-term for thromboembolic events could inhibit vitamin K recycling, disturbing the equilibrium between bone formation and resorption.
Thrombotic events are less frequent among children than adults, but the incidence is rising among children, said the researchers at Maastricht University in the Netherlands.
The rise was due to “augmented occurrence and recognition of thromboembolic events in this age group” by increasingly aware pediatricians.
“It seems that long-term use of coumarin derivatives (coagulants such as warfarin) may cause osteopenia in children with the risk of developing osteoporosis later in life,” they concluded.
K block
The study compared 23 children taking anticoagulants with a control group of 25. Values of coagulation factors were lower in patients than in controls, because of oral anticoagulant (OAC) therapy.
The study group were aged between five and 18 years (median age of 11) and had all undergone OAC therapy with 16 being given warfarin and seven acenocoumarol. None had any history of bone disease.
Bone mass density of the lumbar spine (L1-L4) was assessed using Dual Energy x-ray Absorptiometry (DEXA Scanning) and was expressed as z score. A healthy z score is zero. The median z score of the study group was -1.065.
While none of the patients suffered from osteoporosis, 12 (52%) displayed signs of osteopenia.
A previous study that found monkeys that displayed normal bone density after being given warfarin could not be extrapolated to humans, “who are different organisms”.
Two other studies with children had noted a reduction in bone mass density.
"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 Leon J Schurgers, senior scientist from VitaK, at Maastricht University.
Dr Schurgers added: "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 per cent impaired matrix Gla-protein is present."
“This would explain [another] study, showing that high intake of vitamin K2 reduced cardiovascular disease by some 50 per cent. 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."
The researchers said studies were needed to indicate whether a single bone marker could be used to predict osteoporosis in children.
It would be reasonable to closely monitor bone status of children on coumarin treatment using a combination of bone markers and other techniques to “intervene when necessary with appropriate nutritional or pharmacologic regimens.”
“Multicenter studies are needed to indicate whether a single bone marker could be used to predict osteoporosis in children,” they wrote.
Source:
Journal of Pediatric Hematology/Oncology
30(8):592-597, August 2008.Authors: Avgeri, Maria MD; Papadopoulou, Anna PhD; Platokouki, Helen MD, PhD; Douros, Kostas MD; Rammos, Spyridon MD, PhD; Nicolaidou, Polyxeni MD, PhD; Aronis, Sophia MD, PhD.