The effect of osteogenic protein-1 dosing regimen on ectopic bone formation

Osteogenic protein-1 (also known as bone morphogenetic protein-7) is a member of the bone morphogenetic protein family. Several of the bone morphogenetic proteins, including osteogenic protein-1, have been shown to form bone at an ectopic site. However, optimal dosing regimens for the use of osteogenic protein-1 and other bone morphogenetic proteins in large bone defects have not been determined conclusively. We investigated the influence of osteogenic protein-1 (at doses of 0.1, 1, and 10 microg) with dosing regimens of single bolus, continuous infusion (alone), or bolus and continuous infusion in the rat ectopic subcutaneous bone formation assay (alkaline phosphatase units per microgram protein) in the presence of demineralized bone matrix. The biochemical results showed that the single bolus dosing regimen was significantly more effective than the continuous infusion alone and as effective as the bolus and continuous infusion regimens. The quality of the bone histologically confirmed the biochemical results. These data show that osteogenic protein-1 given as a single bolus is more effective in forming bone at an ectopic site than a continuous infusion of this protein.