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The Journal of Bone and Joint Surgery, Vol 77, Issue 5 734-750, Copyright © 1995 by Journal of Bone and Joint Surgery, Inc
Effect of recombinant human osteogenic protein-1 on healing of segmental defects in non-human primates
SD Cook, MW Wolfe, SL Salkeld and DC Rueger
Department of Orthopaedic Surgery, Tulane University School of Medicine, New Orleans, Louisiana 70112-2699, USA.
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)
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