Serum levels of the fetuin-mineral complex correlate with artery calcification in the rat.

The present studies were carried out to evaluate the possible association between the presence of the fetuin-mineral complex in serum and vitamin D-induced artery calcification. The first experiment shows that there is a fetuin-mineral complex in the blood of rats in which extensive calcification of the artery media has been induced by treatment with vitamin D for 96 h, and that there is no detectable fetuin-mineral complex in the blood of rats in which artery calcification has been inhibited by concurrent treatment with ibandronate or osteoprotegerin. The second experiment shows that the timing of vitamin D-induced artery calcification correlates with the timing of the maximal increase in serum fetuin-mineral complex levels. Whereas both results indicate that serum levels of the fetuin-mineral complex are indeed associated with vitamin D-induced artery calcification, the biochemical basis for this association is presently unclear. One possibility is that high levels of the fetuin-mineral complex cause defects in the ability of fetuin to prevent the growth of the mineral component, which then seeds artery calcification. Another possibility is that the fetuin-mineral complex is the downstream product of a pathway that begins with the true causative agent, and that the serum level of the fetuin-mineral complex is a marker for the activity of this agent in blood. An unexpected finding of the present studies is that vitamin D-induced artery calcification is also correlated with a 65 to 75% reduction in serum fetuin, a reduction that appears to be caused by the clearance of the fetuin-mineral complex from serum.