Effect of recombinant human osteogenic protein-1 on the healing of a freshly closed diaphyseal fracture

• Published in: Bone (New York, N.Y.) Vol. 31; no. 1; pp. 158 - 164
• Main Authors: Den Boer, F.C, Bramer, J.A.M, Blokhuis, T.J, Van Soest, E.J, Jenner, J.M.G.T, Patka, P, Bakker, F.C, Burger, E.H, Haarman, H.J.T.M
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01-07-2002; Elsevier Science
• Subjects: Absorptiometry, Photon - methods; Animals; Biological and medical sciences; Bone morphogenetic protein (BMP); Bone Morphogenetic Protein 7; Bone Morphogenetic Proteins - therapeutic use; Bone repair; Bones, joints and connective tissue. Antiinflammatory agents; Diaphyses - diagnostic imaging; Diaphyses - injuries; Female; Fracture healing; Goats; Growth factors; Humans; Medical sciences; Osteogenic protein-1 (OP-1); Pharmacology. Drug treatments; Recombinant Proteins - therapeutic use; Tibial Fractures - diagnostic imaging; Tibial Fractures - drug therapy; Tissue engineering; Tomography, X-Ray Computed - methods; Transforming Growth Factor beta; Bone repair; Bone morphogenetic protein (BMP); Fracture healing; Tissue engineering; Growth factors; Osteogenic protein-1 (OP-1); Animal model; Hindlimb; Diseases of the osteoarticular system; Fracture; Diaphysis; Consolidation; Three dimensional representation; Tibia; Goat; Ungulata; Biomedical engineering; Evaluation; Treatment efficiency; Induced fracture; Mechanical properties; Histology; Radiography; Vertebrata; Chemotherapy; Mammalia; Bone morphogenetic protein; Treatment; Computerized axial tomography; Artiodactyla; Bone
• ISSN: 8756-3282; 1873-2763
• DOI: 10.1016/S8756-3282(02)00816-5

Osteogenic protein-1 (OP-1), or bone morphogenetic protein-7, is an osteoinductive morphogen that is involved in embryonic skeletogenesis and in bone repair. In bone defect models without spontaneous healing, local administration of recombinant human OP-1 (rhOP-1) induces complete healing. To investigate the ability of rhOP-1 to accelerate normal physiologic fracture healing, an experimental study was performed. In 40 adult female goats a closed tibial fracture was made, stabilized with an external fixator, and treated as follows: (1) no injection; (2) injection of 1 mg rhOP-1 dissolved in aqueous buffer; (3) injection of collagen matrix; and (4) injection of 1 mg rhOP-1 bound to collagen matrix. The test substances were injected in the fracture gap under fluoroscopic control. At 2 and 4 weeks, fracture healing was evaluated with radiographs, three-dimensional computed tomography (CT), dual-energy X-ray absorptiometry, biomechanical tests, and histology. At 2 weeks, callus diameter, callus volume, and bone mineral content at the fracture site were significantly increased in both rhOP-1 groups compared with the no-injection group. As signs of accelerated callus maturation, bending and torsional stiffness were higher and bony bridging of the fracture gap was observed more often in the group with rhOP-1 dissolved in aqueous buffer than in uninjected fractures. Treatment with rhOP-1 plus collagen matrix did not result in improved biomechanical properties or bony bridging of the fracture gap at 2 weeks. At 4 weeks there were no differences between groups, except for a larger callus volume in the rhOP-1 plus collagen matrix group compared with the control groups. All fractures showed an advanced stage of healing at 4 weeks. In conclusion, the healing of a closed fracture in a goat model can be accelerated by a single local administration of rhOP-1. The use of a carrier material does not seem to be crucial in this application of rhOP-1.