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ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #58975
Title: UNDERCARBOXYLATED OSTEOCALCIN: DEVELOPMENT OF A METHOD TO DETERMINE VITAMIN K STATUS

Author
item SOKOLL, LORI - TUFTS-HNRCA
item O'BRIEN, MAUREEN - TUFTS-HNRCA
item CAMILO, MARIA - UNIVERSITY OF LISBON
item SADOWSKI, JAMES - TUFTS-HNRCA

Submitted to: Clinical Chemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/1/1995
Publication Date: N/A
Citation: N/A

Interpretive Summary: Until recently the only known function for vitamin K was in the regulation of blood clot formation. However, it is now known that the vitamin has a much larger role and is involved in the synthesis of many proteins throughout the body. One of these proteins, osteocalcin, is found in bone and thought to play a role in the maintenance of healthy bones. Vitamin K acts on the bone protein to make it bind to the calcium present in bone. When vitamin K is absent or antagonized by the blood thinner Warfarin, the bone protein cannot bind to the calcium in bone. We capitalized on this observation and developed a test that can distinguish between the bone protein that can bind to bone and that which cannot bind to bone. We studied the effect of the blood thinner (1mg/day) on the bone protein's ability to bind to calcium in nine healthy elderly subjects aged 60 to 80. The percentage of the bone protein that failed to bind to bone calcium increased almost 200% after treatment with the blood thinner. This dose of the blood thinner is so low that it has no effect on any laboratory tests for blood clotting. However, the binding test for the bone protein was very responsive and promises to be a very good laboratory test for the determination of vitamin K nutritional status. We are conducting further experiments to determine whether or not this test will be a predictor of vitamin K status.

Technical Abstract: A radioimmunoassay was developed utilizing a polyclonal antibody against bovine osteocalcin which has a carboxy terminal epitope and can recognize both native and descarboxy osteocalcin. Dis- crimination of these two forms of osteocalcin was achieved using adsorption to barium sulfate,taking advantage of the calcium binding properties of the vitamin K-dependent gla domain. To test the clinical application of undercarboxylated osteocalcin, the effect of minidose warfarin on this measure was examined in 9 healthy subjects ages 60 to 80 years. The percentage of under- carboxylated osteocalcin increased 170 +/- 36% (mean +/- SEM) after 7 days treatment with 1 mg/day warfarin. The effectiveness of undercarboxylated osteocalcin as a sensitive measure of vitamin K nutritional status was further established when levels dropped to 17 +/- 14% below baseline with 2 days of repletion with 5 mg/day of vitamin K1 while prothrombin times did not leave the normal range.