Posterolateral lumbar intertransverse process spine arthrodesis with recombinant human bone morphogenetic protein 2/hydroxyapatite-tricalcium phosphate after laminectomy in the nonhuman primate.
METHODS
A nonhuman primate lumbar intertransverse process arthrodesis model was used to evaluate recombinant human bone morphogenetic protein 2 (rhBMP-2) in a hydroxyapatite-tricalcium phosphate (HA-TCP) carrier as a complete bone graft substitute.


OBJECTIVE
To assess the ability of a ceramic material to serve as a carrier for various doses of rhBMP-2 as a bone graft substitute in a primate model of posterolateral intertransverse process spinal fusion after laminectomy.


BACKGROUND
The reported non-union rates for posterolateral lumbar spine fusion with autogenous iliac crest bone range from 5-35%. Recombinant human bone morphogenetic protein 2 has shown potential to serve as a bone graft substitute for posterolateral intertransverse process spine fusion. Although a resorbable collagen sponge was a suitable carrier in rabbits and dogs, it was too compressible for the paraspinal muscles in rhesus monkeys. This failure of the collagen carrier has prompted evaluation of the feasibility of an alternative carrier material and the required dose of rhBMP-2.


METHODS
Twenty-one adult rhesus monkeys underwent a laminectomy at L4-L5 followed by bilateral intertransverse process arthrodesis via the same midline incision (n = 16) or a minimally invasive video-assisted posterolateral approach (n = 5). Bone graft implants on each side consisted of either 5 cm3 of autogenous iliac crest bone or 60:40 HA-TCP blocks (1.2 x 0.5 x 3.7 cm) loaded with a solution containing 0, 6, 9, or 12 mg of rhBMP-2 per side. The monkeys were killed 24 weeks after surgery. Inspection, manual palpation, radiography, and histology were used to assess fusion and to detect any bony growth into the laminectomy defect.


RESULTS
Fusion was not achieved in any of the monkeys treated with autogenous iliac crest bone graft. Both of the monkeys treated with the HA-TCP blocks with 0 mg rhBMP-2 achieved fusion. All 15 monkeys treated with the HA-TCP blocks and either of the three doses of rhBMP-2 achieved solid fusion. Two animals had extension of the fusion on one side because of malpositioned ceramic block. The results in animals fused via the minimally invasive video-assisted technique were the same as inthose fused with the open technique. Histologic analysis showed some ingrowth of bone into the ends but not-through the ceramic block in the absence of rhBMP-2. When the ceramic blocks were loaded with rhBMP-2 there was a dose-dependent increase in the amount and quality of bone throughout the ceramic carrier based on qualitative assessment. No significant bone encroachment on the exposed thecal sac through the laminectomy defect was observed in any of the monkeys.


CONCLUSIONS
Hydroxyapatite-tricalcium phosphate proved to be a suitable carrier for rhBMP-2 in the posterolateral spine fusion model in rhesus monkeys. Even in the presence of a laminectomy defect, there was no evidence of bone induction outside the confines of the ceramic carrier.
Boden
S D
SD
Department of Orthopaedic Surgery, Emory University School of Medicine, USA.
Martin
G J
GJ
Morone
M A
MA
Ugbo
J L
JL
Moskovitz
P A
PA
D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000627:therapeutic use*; D018786:Bone Substitutes / Q000627:therapeutic use*; D002130:Calcium Phosphates / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D006882:Hydroxyapatites / Q000627:therapeutic use*; D007085:Ilium / Q000637:transplantation; D007796:Laminectomy; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology / Q000601:surgery*; D008253:Macaca mulatta; D016348:Osseointegration / Q000187:drug effects; D011994:Recombinant Proteins / Q000627:therapeutic use; D013123:Spinal Fusion; D014057:Tomography, X-Ray Computed; D016212:Transforming Growth Factor beta
C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D018786:Bone Substitutes; D002130:Calcium Phosphates; D004337:Drug Carriers; D006882:Hydroxyapatites; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C094280:hydroxyapatite-tricalciumphosphate composite