title: rhBMP-2 injected in a calcium phosphate paste (alpha-BSM) accelerates healing in the rabbit ulnar osteotomy model.
abstract: This study evaluated the ability of recombinant human bone morphogenetic protein-2 (rhBMP-2) delivered in an injectable calcium phosphate carrier (alpha-BSM) to accelerate healing in a rabbit ulna osteotomy model compared to untreated surgical controls. Healing was assessed by radiography, histology and biomechanics. Bilateral mid-ulnar osteotomies were created in 16 skeletally mature rabbits. One limb in each animal was injected with either 0.1 mg rhBMP-2/alpha-BSM (BMP) (N=8) or buffer/alpha-BSM (BSM) (N=8). Contralateral osteotomies served as untreated surgical controls (SXCT). Gamma scintigraphy showed 75%, 45% and 5% of the initial 125I-rhBMP-2 dose was retained at the osteotomy site at 3 h, 1 week and 3 weeks. The biological activity of rhBMP-2 (alkaline phosphatase activity from bioassay) extracted from alpha-BSM incubated in vitro up to 30 days at 37 degrees C was unchanged. Radiographs demonstrated complete bridging of the BMP limbs at 4 weeks whereas none of the BSM or SXCT limbs were bridged. Post-mortem peripheral quantitative computed tomography determined mineralized callus area was 62% greater in BMP limbs compared to SXCT limbs. Torsional stiffness and strength were 63% and 103% greater in BMP limbs compared to SXCT limbs. There was no difference in torsional properties between BSM and SXCT limbs. Failure occurred outside the osteotomy in four out of seven of the BMP limbs. All BSM and SXCT limbs failed through the osteotomy. Histology showed bony bridging of the osteotomy and no residual carrier in the BMP limbs. BSM and SXCT groups showed less mature calluses composed of primarily fibrocartilaginous tissue and immature bone in the osteotomy gap. These data indicate rhBMP-2 delivered in alpha-BSM accelerated healing in a rabbit ulna osteotomy model compared to BSM and SXCT groups.
authors.affiliation: Wyeth Research, 200 Cambridge Park Drive, Cambridge, MA 02140, USA. rli@wyeth.com
authors.forename: R H
authors.initials: RH
authors.lastname: Li
authors.forename: M L
authors.initials: ML
authors.lastname: Bouxsein
authors.forename: C A
authors.initials: CA
authors.lastname: Blake
authors.forename: D
authors.initials: D
authors.lastname: D'Augusta
authors.forename: H
authors.initials: H
authors.lastname: Kim
authors.forename: X J
authors.initials: XJ
authors.lastname: Li
authors.forename: J M
authors.initials: JM
authors.lastname: Wozney
authors.forename: H J
authors.initials: HJ
authors.lastname: Seeherman
mesh_terms: D000818:Animals; D001843:Bone Cements / Q000494:pharmacology*; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D002146:Bony Callus / Q000187:drug effects / Q000473:pathology; D002130:Calcium Phosphates / Q000494:pharmacology*; D004195:Disease Models, Animal; D004337:Drug Carriers; D004548:Elasticity / Q000187:drug effects; D017102:Fracture Healing / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D010027:Osteotomy / Q000379:methods; D011817:Rabbits; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D013718:Tensile Strength / Q000187:drug effects / Q000502:physiology; D014102:Torsion Abnormality / Q000503:physiopathology; D016212:Transforming Growth Factor beta; D014457:Ulna / Q000187:drug effects* / Q000503:physiopathology; D014458:Ulna Fractures / Q000188:drug therapy / Q000503:physiopathology
chemical_list: C525718:BMP2 protein, human; D001843:Bone Cements; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D002130:Calcium Phosphates; D004337:Drug Carriers; 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