[New-bone formation by osteogenic protein-1 and autogenic bone marrow in a critical tibial defect model in sheep].
OBJECTIVE
Osteogenic Protein-1 (OP-1) is known to be a very potent osteoinductive growth factor. However, experimental studies using critical-size defect models in the weight-bearing lower extremity show non-uniform results. Therefore, we studied the osteoinductivity of OP-1 in a tibial worst-case defect model in sheep. Potential improvement of OP-1 induced new bone formation using a composite graft with autogenous bone marrow was to be investigated.


METHODS
In 19 sheep a 5 cm segmental defect of the tibial diaphysis was treated by intramedullary nailing and filled with the following implants: 5 mg OP-1 + inactivated demineralized bone matrix (group 1; n = 6); 5 mg OP-1 + inactivated demineralized bone matrix + 5 ml autogenous bone marrow (group 2; n = 5); autogenous cancellous bone (group 3; n = 4), or inactivated demineralized bone matrix + 5 ml autogenous bone marrow (group 4; n = 4).


RESULTS
In total, 3 out of 10 defect sites treated with OP-1 were completely bridged radiographically by 12 weeks. Initially, x-rays showed accelerated new bone formation by use of the composite grafts containing OP-1 and autogenous bone marrow. However, 12 weeks post surgery 3D-CT-volumetry could not detect significant differences of new bone formation within the defect sites treated by OP-1 with or without bone marrow, while new bone formation by autogenous cancellous bone was better than by OP-1.


CONCLUSIONS
In our worst case defect model, the osteoinductive potential of OP-1 is initially accelerated but 12 weeks post surgery not increased when combined with autogenous bone marrow transplantation. So far, critical segmental bone defects of the weight-bearing lower extremity can not be bridged regularly in our model by use of OP-1. Therefore, for the treatment of such critical defects with rotational instability the examined application device of OP-1 can not yet be recommended.
Regauer
M
M
Chirurgische Klinik und Poliklinik Innenstadt, München.
Jürgens
I
I
Kotsianos
D
D
Stützle
H
H
Mutschler
W
W
Schieker
M
M
D000818:Animals; D016026:Bone Marrow Transplantation; D001857:Bone Matrix / Q000637:transplantation; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000008:administration & dosage*; D018786:Bone Substitutes; D016025:Bone Transplantation; D005500:Follow-Up Studies; D005594:Fracture Fixation, Intramedullary / Q000295:instrumentation / Q000379:methods*; D017102:Fracture Healing; D020007:Implants, Experimental; D016348:Osseointegration; D010012:Osteogenesis; D010027:Osteotomy; D012756:Sheep; D013234:Stem Cells / Q000502:physiology; D013978:Tibial Fractures / Q000000981:diagnostic imaging / Q000601:surgery*; D013997:Time Factors; D036542:Tomography, Spiral Computed; D016212:Transforming Growth Factor beta / Q000008:administration & dosage*
D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D018786:Bone Substitutes; D016212:Transforming Growth Factor beta