Effects of OP-1 and PTH in a new experimental model for the study of metaphyseal bone healing

Authors

  • Eleftherios Tsiridis,

    1. Department of Orthopaedic Surgery, Boston University Medical Center, Laboratory of Orthopaedic Research, 715 Albany Street, R-205, Boston, Massachusetts 02118
    Search for more papers by this author
  • Elise F. Morgan,

    Corresponding author
    1. Department of Orthopaedic Surgery, Boston University Medical Center, Laboratory of Orthopaedic Research, 715 Albany Street, R-205, Boston, Massachusetts 02118
    2. Department of Aerospace and Mechanical Engineering, Boston University, 110 Cummington Street, Boston, Massachusetts 02215
    • Department of Orthopaedic Surgery, Boston University Medical Center, Laboratory of Orthopaedic Research, 715 Albany Street, R-205, Boston, Massachusetts 02118 Telephone: 617-353-2791.
    Search for more papers by this author
  • Jared M. Bancroft,

    1. Department of Orthopaedic Surgery, Boston University Medical Center, Laboratory of Orthopaedic Research, 715 Albany Street, R-205, Boston, Massachusetts 02118
    Search for more papers by this author
  • Mike Song,

    1. Department of Orthopaedic Surgery, Boston University Medical Center, Laboratory of Orthopaedic Research, 715 Albany Street, R-205, Boston, Massachusetts 02118
    Search for more papers by this author
  • Michael Kain,

    1. Department of Orthopaedic Surgery, Boston University Medical Center, Laboratory of Orthopaedic Research, 715 Albany Street, R-205, Boston, Massachusetts 02118
    Search for more papers by this author
  • Louis Gerstenfeld,

    1. Department of Orthopaedic Surgery, Boston University Medical Center, Laboratory of Orthopaedic Research, 715 Albany Street, R-205, Boston, Massachusetts 02118
    Search for more papers by this author
  • Thomas A. Einhorn,

    1. Department of Orthopaedic Surgery, Boston University Medical Center, Laboratory of Orthopaedic Research, 715 Albany Street, R-205, Boston, Massachusetts 02118
    Search for more papers by this author
  • Mary L. Bouxsein,

    1. Orthopedic Biomechanics Laboratory, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, RN 115, Boston, Massachusetts 02215
    Search for more papers by this author
  • Paul Tornetta III

    1. Department of Orthopaedic Surgery, Boston University Medical Center, Laboratory of Orthopaedic Research, 715 Albany Street, R-205, Boston, Massachusetts 02118
    Search for more papers by this author

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 µg OP-1 was mixed in with the TCP. Groups 2 and 3 received daily subcutaneous injections of 10 and 40 µg/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. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 25:1193–1203, 2007

Ancillary