Systemic Regulation of Distraction Osteogenesis: A Cascade of Biochemical Factors

Authors

  • S. Weiss M.D.,

    Corresponding author
    1. Stiftung Orthopädische Universitätsklinik, Ruprecht-Karls-Universität Heidelberg, Schlierbacher Landstraβe 200a, Heidelberg-Schlierbach, Germany
    • Stiftung Orthopädische Universitätsklinik, Ruprecht-Karls-Universität Heidelberg, Schlierbacher Landstraβe 200a, 69118 Heidelberg-Schlierbach, Germany
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  • R. Baumgart,

    1. Chirurgische Klinik und Poliklinik, Klinikum Innenstadt Ludwig-Maximilians-Universität München, Nuβbaumstrasse 20, München, Germany
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  • M. Jochum,

    1. Abteilung für Klinische Chemie und Klinische Biochemie Chirurgische Klinik und Poliklinik, Klinikum Innenstadt, Ludwig-Maximilians-Universität München, Nuβbaumstrasse 20, München, Germany
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  • C. J. Strasburger,

    1. Medizinische Klinik, Klinikum Innenstadt Ludwig-Maximilians-Universität München, Ziemsenstrasse 1, München, Germany
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  • M. Bidlingmaier

    1. Medizinische Klinik, Klinikum Innenstadt Ludwig-Maximilians-Universität München, Ziemsenstrasse 1, München, Germany
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  • Presented in part at the 10th annual scientific meeting of the Association for the Study and Application of the Methods of Ilizarov-North America, Orlando, Florida, USA, 2000.

  • The authors have no conflict of interest.

Abstract

This study investigates the systemic biochemical regulation of fracture healing in distraction osteogenesis compared with rigid osteotomy in a prospective in vivo study in humans. To further clarify the influence of mechanical strain on the regulation of bone formation, bone growth factors (insulin-like growth factor [IGF] I, IGF binding protein [IGFBP] 3, transforming growth factor [TGF] β1, and basic FGF [bFGF]), bone matrix degrading enzymes (matrix-metalloproteinases [MMPs] 1, 2, and 3), human growth hormone (hGH), and bone formation markers (ALP, bone-specific ALP [BAP], and osteocalcin [OC]) have been analyzed in serum samples from 10 patients in each group pre- and postoperatively. In the distraction group, a significant postoperative increase in MMP-1, bFGF, ALP, and BAP could be observed during the lengthening and the consolidation period when compared with the baseline levels. Osteotomy fracture healing without the traction stimulus failed to induce a corresponding increase in these factors. In addition, comparison of both groups revealed a significantly higher increase in TGF-β1, IGF-I, IGFBP-3, and hGH in the lengthening group during the distraction period, indicating key regulatory functions in mechanotransduction. The time courses of changes in MMP-1, bone growth factors (TGF-β1 and bFGF), and hGH, respectively, correlated significantly during the lengthening phase, indicating common regulatory pathways for these factors in distraction osteogenesis. Significant correlation between the osteoblastic marker BAP, TGF-β1, and bFGF suggests strain-activated osteoblastic cells as a major source of systemically increased bone growth factors during callus distraction. The systemic increase in bFGF and MMP-1 might reflect an increased local stimulation of angiogenesis during distraction osteogenesis.

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