EFFECT OF RECOMBINANT HUMAN OSTEOGENIC PROTEIN-1 ON HEALING OF SEGMENTAL DEFECTS IN NONHUMAN-PRIMATES

The effect of recombinant human osteogenic protein-1 on the healing of segmental bone defects was studied in twenty-eight African green monk eys (Cercopithecus aethiops). A 2.0-centimeter osteoperiosteal defect was created in the middle of the ulnar shaft in fourteen animals and i n the diaphysis of the tibia in the other fourteen. The ulnar defect w as filled with an implant consisting of 1000 micrograms of recombinant human osteogenic protein-1 in 400 milligrams of bovine bone-collagen carrier in six animals, with collagen carrier alone in two animals, an d with autogenous cancellous bone graft from the contralateral tibia a nd femur in six animals. The tibial defect was filled with 250, 500 (t wo tibiae), 1000, or 2000 micrograms of recombinant human osteogenic p rotein-1 in 400 milligrams of collagen carrier in five animals, with c ollagen carrier alone in one animal, and with autogenous cancellous bo ne graft in sis animals; in the two remaining animals (controls), the tibial defect was left unfilled. The tibial defects were stabilized wi th an intramedullary Steinmann pin. All animals were killed at twenty weeks postoperatively Healing of the defects was evaluated with biweek ly radiographs, with histological examination, and with mechanical tes ting. Radiographically, all of the defects that had been treated with recombinant human osteogenic protein-1 exhibited new-bone formation, b ut they differed in the degree of healing and remodeling. Five of the six ulnae treated with recombinant human osteogenic protein-1 and four of the five tibiae treated with this substance exhibited complete hea ling at six to eight weeks, with bridging of the defect by new bone fi rst observed at four weeks. The two unheated defects both exhibited ne w-bone formation but incomplete union, which precluded mechanical test ing, No defect that had been filled with collagen carrier or that had been left unfilled exhibited any signs of healing or major new-bone fo rmation. None of the sis ulnae that had been filled with autogenous bo ne graft exhibited complete healing, compared with five of the six tib iae that had been so treated. Histological evaluation of the defects t reated with recombinant human osteogenic protein-1 revealed the format ion of new cortices with areas of woven and lamellar bone and normal-a ppearing marrow elements at twenty weeks postoperatively. The tibial d efects that had been treated with autogenous bone graft had a similar appearance. All control ulnar and tibial defects and all ulnar defects that had been treated with autogenous bone graft had fibrous union wi th little new-bone formation. Almost complete resorption of the autoge nous bone graft was noted. Mechanical testing of the ulnae and tibiae treated with recombinant human osteogenic protein-1 revealed an averag e torsional strength to failure of 92 per cent and 69 per cent that of the contralateral, intact ulnae and tibiae, respectively. No ulnar de fect that had been treated with autogenous bone graft healed sufficien tly for mechanical testing. The average torsional strength of the tibi ae that had been treated with autogenous bone graft was only 23 per ce nt that of the contralateral, intact tibiae. CLINICAL RELEVANCE: The r ecombinant human osteogenic protein-1 implants used in this study elic ited healing in large segmental bone defects that was as good as or be tter than that achieved with autogenous bone grafts. New-bone formatio n was noted in all defects treated with recombinant human osteogenic p rotein-1. The use of osteoinductive implants to augment or replace bon e grafts in the treatment of segmental bone loss and non-union should reduce the amount of operative intervention and the number of inherent complications associated with autogenous bone-grafting. It should als o circumvent the risk of rejection and infection associated with the u se of allogeneic tissue.