title: Effects of OP-1 and PTH in a new experimental model for the study of metaphyseal bone healing.
abstract: The purpose of this study was to establish a reliable model of metaphyseal bone healing and to use this model to investigate the effect of recombinant human osteogenic protein 1 (rhOP-1; BMP-7) and parathyroid hormone fragment (PTH 1-34) on healing. A wedge-shaped osteotomy was created in the distal tibia of 16-week-old female New Zealand White rabbits (n = 20) and was bridged with a custom-made external fixator. Five experimental groups of four animals each were investigated. In groups 1-4 the osteotomy gap was filled with tricalcium phosphate (TCP), and the gap was left unfilled in group 5 ("normal healing"). In group 1, 200 microg OP-1 was mixed in with the TCP. Groups 2 and 3 received daily subcutaneous injections of 10 and 40 microg/kg PTH, respectively, beginning on postoperative day 1. Radiographs were taken weekly. Following sacrifice on postoperative day 28, peripheral quantitative computed tomography (pQCT), histology, and mechanical testing (axial compression and torsion) were performed. Only one animal failed to complete the full 4-week time course, and no infections were encountered. Bone healing occurred in all animals. OP-1 stimulated bone formation locally, while the lower dose of PTH enhanced bone formation systemically (p < 0.05). Tibiae treated with OP-1 exhibited higher torsional strength (p = 0.04) than those in the normal healing group. These results indicate that a reliable and reproducible surgical model of metaphyseal healing has been established. In addition, differences in systemic versus local effects of PTH and OP-1 in accelerating metaphyseal fracture healing were found.
authors.affiliation: Department of Orthopaedic Surgery, Boston University Medical Center, Laboratory of Orthopaedic Research, 715 Albany Street, R-205, Boston, Massachusetts 02118, USA.
authors.forename: Eleftherios
authors.initials: E
authors.lastname: Tsiridis
authors.forename: Elise F
authors.initials: EF
authors.lastname: Morgan
authors.forename: Jared M
authors.initials: JM
authors.lastname: Bancroft
authors.forename: Mike
authors.initials: M
authors.lastname: Song
authors.forename: Michael
authors.initials: M
authors.lastname: Kain
authors.forename: Louis
authors.initials: L
authors.lastname: Gerstenfeld
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Einhorn
authors.forename: Mary L
authors.initials: ML
authors.lastname: Bouxsein
authors.forename: Paul
authors.initials: P
authors.lastname: Tornetta
mesh_terms: D000818:Animals; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D001861:Bone Regeneration / Q000187:drug effects*; D019245:Compressive Strength; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D017102:Fracture Healing / Q000187:drug effects*; D006801:Humans; D007279:Injections, Subcutaneous; D010027:Osteotomy; D010446:Peptide Fragments / Q000494:pharmacology*; D011817:Rabbits; D011859:Radiography; D011994:Recombinant Proteins; D013314:Stress, Mechanical; D019379:Teriparatide / Q000031:analogs & derivatives* / Q000494:pharmacology; D013977:Tibia / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000293:injuries / Q000473:pathology; D014102:Torsion Abnormality
chemical_list: C525819:BMP7 protein, human; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D010446:Peptide Fragments; D011994:Recombinant Proteins; D019379:Teriparatide; C035748:parathyroid hormone (1-34)amide