Repair of calvarial nonunions by osteogenin, a bone-inductive protein

Efforts were taken to determine the dose of bovine osteogenin (OG) that would induce more bone than that induced by 20 mg of rat particulate demineralized bone matrix (DBM), the amount allowed by the confines of an 8-mm rat craniotomy defect. Dose-response studies were performed for demineralized bone matrix alone and osteogenin, partially purified from bovine demineralized bone matrix, plus rat insoluble collagenous bone matrix (M). Demineralized bone matrix alone (2.5, 5.0, 10, 20, or 40 mg) or osteogenin (0.0625, 0.125, 0.250, 0.50, or 1.0 mg) plus 25 mg insoluble collagenous bone matrix was implanted into the pectoralis muscle for 3, 5, and 7 weeks. Both materials induced time- and dose-dependent formation of bone. The three highest dosages of osteogenin (plus insoluble collagenous bone matrix) induced more bone than 20 mg demineralized bone matrix and seemed to accelerate bone repair. However, when implanted into the 8-mm rat craniotomy defect for 4 weeks, 20 mg demineralized bone matrix and 0.5 mg osteogenin (plus insoluble collagenous bone matrix) induced comparable amounts of bone. These results suggest different mechanisms for bone formation in heterotopic and orthotopic sites.