THE EFFECT OF RECOMBINANT HUMAN OSTEOGENIC PROTEIN-1 ON HEALING OF LARGE SEGMENTAL BONE DEFECTS

A rabbit ulnar non-union model was used to evaluate the effect of reco mbinant human osteogenic protein-1 on the healing of a large segmental osteoperiosteal defect. A 1.5-centimeter segmental defect was created in the mid-part of the ulnar shaft of adult rabbits. The defect was f illed with an implant containing either recombinant human osteogenic p rotein-1 or naturally occurring bovine osteogenic protein. The recombi nant human osteogenic protein-1 implants consisted of a carrier of 125 milligrams of demineralized, guanidine-extracted, insoluble rabbit bo ne matrix (the collagen carrier), reconstituted with 3.13, 6.25, 12.5, twenty-five, fifty, 100, 200, 300, or 400 micrograms of recombinant h uman osteogenic protein-1. Animals that received recombinant human ost eogenic protein-1 were compared with animals that received an implant of 250 micrograms of a preparation of naturally occurring bovine osteo genic protein mixed with the collagen carrier. Limbs that served as co ntrols received either the collagen carrier alone or no implant at all . The treated and the untreated defects were examined radiographically and histologically at eight or twelve weeks after implantation. Mecha nical testing was performed on six animals. All implants of recombinan t human osteogenic protein-1, except for those containing 3.13 microgr ams of the substance, induced complete radiographic osseous union with in eight weeks. The defects that were treated with an implant of bovin e osteogenic protein also healed within this time-period. The bone ind uced by both types of implants had new cortices with advanced remodeli ng and marrow elements. Histological evaluation of this new bone at ei ght weeks postoperatively revealed primarily lamellar bone, with the f ormation of new cortices and normal-appearing marrow elements. The ave rage torsional strength and energy-absorption capacity of the union in duced by recombinant human osteogenic protein-1 was comparable with th at of intact bone. The control defects that had been implanted with co llagen carrier alone and those with no implant showed no bridging of t he defect. CLINICAL RELEVANCE: Segmental bone loss and non-union are c hallenging problems for orthopaedic surgeons. The results of this stud y demonstrate that a highly purified recombinant human osteogenic prot ein is capable of inducing healing in a large bone defect in an animal model. The type of implant used in this study may provide an alternat ive to the use of autogenous graft and allograft bone in the reconstru ction of bone defects caused by trauma, neoplasia, or infection. The u se of osteogenic proteins to augment or replace bone grafts may reduce the number of operations needed to treat such conditions and may circ umvent the risk of transmission of infection that is associated with t he transplantation of allografts and autogenous grafts.