Use of recombinant human bone morphogenetic protein-2 to achieve posterolateral lumbar spine fusion in humans: a prospective, randomized clinical pilot trial: 2002 Volvo Award in clinical studies.
METHODS
A prospective randomized clinical study was conducted.


OBJECTIVE
To determine whether the dose and carrier that were successful in rhesus monkeys could induce consistent radiographic spine fusion in humans.


BACKGROUND
Preclinical studies have demonstrated that recombinant human bone morphogenetic protein-2 (rhBMP-2), an osteoinductive bone morphogenetic protein, is successful at generating spine fusion in rabbits and rhesus monkeys.


METHODS
For this study, 25 patients undergoing lumbar arthrodesis were randomized (1:2:2 ratio) based on the arthrodesis technique: autograft/Texas Scottish Rite Hospital (TSRH) pedicle screw instrumentation (n = 5), rhBMP-2/TSRH (n = 11), and rhBMP-2 only without internal fixation (n = 9). On each side, 20 mg of rhBMP-2 were delivered on a carrier consisting of 60% hydroxyapatite and 40% tricalcium phosphate granules (10 cm /side). The patients had single-level disc degeneration, Grade 1 or less spondylolisthesis, mechanical low back pain with or without leg pain, and at least 6 months failure of nonoperative treatment.


RESULTS
All 25 patients were available for follow-up evaluation (mean, 17 months; range 12-27 months). The radiographic fusion rate was 40% (2/5) in the autograft/TSRH group and 100% (20/20) with rhBMP-2 group with or without TSRH internal fixation ( = 0.004). A statistically significant improvement in Oswestry score was seen at 6 weeks in the rhBMP-2 only group (-17.6; = 0.009), and at 3 months in the rhBMP-2/TSRH group (-17.0; = 0.003), but not until 6 months in the autograft/TSRH group (-17.3; = 0.041). At the final follow-up assessment, Oswestry improvement was greatest in the rhBMP-2 only group (-28.7, < 0.001). The SF-36 Pain Index and PCS subscales showed similar changes.


CONCLUSIONS
This pilot study is the first with at least 1 year of follow-up evaluation to demonstrate successful posterolateral spine fusion using a BMP-based bone graft substitute, with radiographs and CT scans as the determinant. Consistently, rhBMP-2 was able to induce bone in the posterolateral lumbar spine when delivered at a dose of 20 mg per side with or without the use of internal fixation. Patients with spondylolisthesis classified higher than Meyerding Grade 1 or with more than 5 mm of translational motion may still require internal fixation. Some patients did smoke during the postoperative period, and all in the rhBMP-2 groups still obtained solid fusions.


CONCLUSIONS
Consistently, rhBMP-2 with the biphasic calcium phosphate granules induced radiographic posterolateral lumbar spine fusion with or without internal fixation in patients whose spondylolisthesis did not exceed Grade 1. Statistically greater and quicker improvement in patient-derived clinical outcome was measured in the rhBMP-2 groups.
Boden
Scott D
SD
Emory Spine Center, Atlanta, Georgia, USA.
Kang
James
J
Sandhu
Harvinder
H
Heller
John G
JG
D001363:Awards and Prizes; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000627:therapeutic use*; D018786:Bone Substitutes / Q000008:administration & dosage*; D016025:Bone Transplantation / Q000009:adverse effects; D002130:Calcium Phosphates / Q000008:administration & dosage; D004343:Drug Implants / Q000009:adverse effects; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007085:Ilium / Q000637:transplantation; D016268:Internal Fixators; D007405:Intervertebral Disc Displacement / Q000601:surgery*; D017116:Low Back Pain / Q000209:etiology; D008161:Lumbosacral Region; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000627:therapeutic use*; D012086:Reoperation; D013123:Spinal Fusion / Q000009:adverse effects / Q000379:methods*; D016212:Transforming Growth Factor beta; D016896:Treatment Outcome
C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D018786:Bone Substitutes; D002130:Calcium Phosphates; D004343:Drug Implants; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C485828:alpha-tricalcium phosphate; C499469:recombinant human bone morphogenetic protein-2; C485830:tetracalcium phosphate; C485838:calcium phosphate, monobasic, anhydrous; C020243:calcium phosphate; C485829:calcium phosphate, dibasic, anhydrous