Pronounced Elevation of Undercarboxylated Osteocalcin in Healthy Children

Abstract

ABSTRACT:The vitamin K-dependent protein osteocalcin is thought to play an important role in bone metabolism. Osteocalcin contains glutamic acid (Gla) residues, which have a high affinity for calcium. Vitamin K acts as an indispensable cofactor for the formation of these residues. Inadequate dietary vitamin K intake results in the synthesis of undercarboxylated (i.e. inactive) osteocalcin (ucOC). In adults, low vitamin K status of bone is associated with low bone density and increased risk of osteoporotic fractures. Little is known about vitamin K status and bone health in children. We used a cross-sectional study design to compare the vitamin K status of bone in healthy children (n ϭ 86) with that of adults (n ϭ 30). In children, a marked elevation of the ratio of ucOC/carboxylated osteocalcin (cOC), indicative of a poor vitamin K status, was observed. This difference persisted after adjusting for age, gender, puberty, height, weight. Furthermore, a marked correlation between the bone markers for bone metabolism and ucOC and cOC was found in the children's group. These findings suggest a pronounced low vitamin K status of bone during growth. The question remains, however, whether children would benefit from higher vitamin K intake, for instance, by improved bone health or stronger bones. V itamin K and vitamin K-dependent proteins (also known as Gla proteins) are best known for their role in blood coagulation. However, Gla proteins are also involved in other physiologic processes (e.g. bone metabolism) (1,2). Osteocalcin is a bone Gla protein and synthesized by osteoblasts (3). It constitutes approximately 20% of the noncollagenous protein found in human bone (4).Vitamin K acts as a cofactor in the posttranslational carboxylation of all Gla proteins. In this process, glutamate residues are converted into ␥-carboxyglutamate (Gla) (5). Gla residues have a high affinity for calcium, and their complex formation with calcium ions was demonstrated to be essential for the function of all Gla proteins currently known.To adequately carboxylate osteocalcin, the osteoblast requires sufficient vitamin K (6). In case of vitamin K deficiency, ucOC will be produced. Bioavailable vitamin K is mainly derived from nutritional sources. The gut flora also produces vitamin K, but at the site of synthesis (colon) its absorption is negligible (7,8). The two most important forms of vitamin K are phylloquinone (vitamin K 1 ) and the group of K 2 vitamins (menaquinones). Dietary sources of phylloquinone are green vegetables (spinach, broccoli) and some plant oils (9). Menaquinones are found in meat and fermented foods like cheese (10). Hence, inadequate intake of vitamin K will lead to the production of undercarboxylated (i.e. inactive) Gla proteins.Methods have been developed to distinguish between cOC and ucOC fractions of osteocalcin (11,12). The ratio between ucOC and cOC (UCR) as well as circulating ucOC levels are used as indicators for the vitamin K status of bone (2,13,14). The UCR is probably the most sensitive marker for bone ...

Impact of skeletal maturation on bone metabolism biomarkers and bone mineral density in healthy Brazilian male adolescents

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Undercarboxylated Osteocalcin as an Indirect Marker of Vitamin K Status in Girls in Various Pubertal Stages

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