The present study was carried out to characterize the fetuin-mineral complex (FMC), a high molecular weight complex of calcium phosphate mineral and the proteins fetuin and matrix Gla protein (MGP) that was initially discovered in serum of rats treated with etidronate, and appears to play a critical role in inhibiting calcification in vivo. Fetuin purified from the FMC contains 3.3 moles of protein-bound phosphate. There is 1.3mg FMC per ml serum 6h after etidronate injection, and the FMC is

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... fetuin and 53% mineral by weight. Formation of the FMC in the first 6h after etidronate injection does not increase serum fetuin in spite of the fact that 50% of serum fetuin is associated with the FMC, and clearance of the FMC in the 9 to 24h interval lowers total serum fetuin by 50%. These observations suggest that the fetuin component of the FMC is derived from fetuin initially in serum, and that clearance of the FMC removes the associated fetuin from circulation. One additional protein was consistently present in all preparations of the FMC, secreted phosphoprotein 24 (spp24). This 24kDa protein is similar in domain structure to fetuin and, like fetuin and MGP, contains several residues of phosphoserine and accumulates in bone. Exogenous spp24 associated strongly with the FMC when added to serum containing it. These observations suggest that spp24 may, like fetuin and MGP, play a role in inhibiting calcification.