Effect of recombinant human osteogenic protein-1 on healing of segmental defects in non-human primates.
The effect of recombinant human osteogenic protein-1 on the healing of segmental bone defects was studied in twenty-eight African green monkeys (Cercopithecus aethiops). A 2.0-centimeter osteoperiosteal defect was created in the middle of the ulnar shaft in fourteen animals and in the diaphysis of the tibia in the other fourteen. The ulnar defect was 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, and with autogenous cancellous bone graft from the contralateral tibia and femur in six animals. The tibial defect was filled with 250, 500 (two tibiae), 1000, or 2000 micrograms of recombinant human osteogenic protein-1 in 400 milligrams of collagen carrier in five animals, with collagen carrier alone in one animal, and with autogenous cancellous bone graft in six animals; in the two remaining animals (controls), the tibial defect was left unfilled. The tibial defects were stabilized with an intramedullary Steinmann pin. All animals were killed at twenty weeks postoperatively. Healing of the defects was evaluated with biweekly radiographs, with histological examination, and with mechanical testing. Radiographically, all of the defects that had been treated with recombinant human osteogenic protein-1 exhibited new-bone formation, but 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 healing at six to eight weeks, with bridging of the defect by new bone first observed at four weeks. The two unhealed defects both exhibited new-bone formation but incomplete union, which precluded mechanical testing. No defect that had been filled with collagen carrier or that had been left unfilled exhibited any signs of healing or major new-bone formation. None of the six ulnae that had been filled with autogenous bone graft exhibited complete healing, compared with five of the six tibiae that had been so treated. Histological evaluation of the defects treated with recombinant human osteogenic protein-1 revealed the formation of new cortices with areas of woven and lamellar bone and normal-appearing marrow elements at twenty weeks postoperatively. The tibial defects 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 with little new-bone formation.(ABSTRACT TRUNCATED AT 400 WORDS)
Cook
S D
SD
Department of Orthopaedic Surgery, Tulane University School of Medicine, New Orleans, Louisiana 70112-2699, USA.
Wolfe
M W
MW
Salkeld
S L
SL
Rueger
D C
DC
D000818:Animals; D001846:Bone Development / Q000187:drug effects; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D016723:Bone Remodeling / Q000187:drug effects; D002417:Cattle; D002522:Chlorocebus aethiops; D003094:Collagen; D004337:Drug Carriers; D011506:Proteins / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D011859:Radiography; D011994:Recombinant Proteins / Q000627:therapeutic use; D013718:Tensile Strength; D013977:Tibia / Q000000981:diagnostic imaging / Q000293:injuries / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000627:therapeutic use*; D014182:Transplantation, Autologous; D014457:Ulna / Q000000981:diagnostic imaging / Q000293:injuries / Q000502:physiology; D014945:Wound Healing / Q000187:drug effects*
C525819:BMP7 protein, human; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D004337:Drug Carriers; D011506:Proteins; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D003094:Collagen