gms | German Medical Science

Joint German Congress of Orthopaedics and Trauma Surgery

02. - 06.10.2006, Berlin

Cytokine activity in sera of patients with delayed fracture healing

Meeting Abstract

  • G. Zimmermann - BG-Unfallklinik Ludwigshafen Unfallchirurgie, Universität Heidelberg, Ludwigshafen, Germany
  • C. Wagner - BG-Unfallklinik Ludwigshafen Unfallchirurgie, Universität Heidelberg, Ludwigshafen, Germany
  • S. Weiss - Orthopädische Universitätsklinik Heidelberg-Schlierbach, Universität Heidelberg, Heidelberg, Germany
  • M. Hänsch - Institut für Immunologie, Universität Heidelberg, Heidelberg, Germany
  • A. Wentzensen - BG-Unfallklinik Ludwigshafen Unfallchirurgie, Universität Heidelberg, Ludwigshafen, Germany
  • S. Zimmermann - Institut für Immunologie, Universität Heidelberg, Heidelberg, Germany

Deutscher Kongress für Orthopädie und Unfallchirurgie. 70. Jahrestagung der Deutschen Gesellschaft für Unfallchirurgie, 92. Tagung der Deutschen Gesellschaft für Orthopädie und Orthopädische Chirurgie und 47. Tagung des Berufsverbandes der Fachärzte für Orthopädie. Berlin, 02.-06.10.2006. Düsseldorf, Köln: German Medical Science; 2006. DocE.4.1-1132

The electronic version of this article is the complete one and can be found online at:

Published: September 28, 2006

© 2006 Zimmermann et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.



Background: Transforming growth factor beta (TGFß) and bone morphogenic proteins (BMP) are crucial for fracture healing. In a previous study we showed that systemic TGFß levels were decreased in patients with delayed fracture union; BMPs, in contrast, were not detected in the serum by ELISA. In the present study we addressed the question whether serum of patients treated with BMP 7 with fractures of long bones contained a proliferation-inducing activity.

Patients and methods:From patients with either normal (group 1) or delayed fracture healing (group 2), or from patients with non-healing fractures, who were treated with local implantation of BMP-7 (group 3) serum samples were collected 1,2,4,8 and 12 weeks after the fracture, and again after 1 year; the latter serving as baseline values. There were 10 patients in each group matched for age, sex, fracture localisation and fixation. The functional activity of the serum samples was tested using a model cell line CCL64, which either proliferates in response to certain cytokines, or differentiates, as seen by growth arrest. The cells were kept in minimal medium for growth arrest and synchronisation and then suspended in cell culture medium supplemented with 10 % patients serum and cell proliferation was measured after 72 h by incorporation of 3H-thymidine. TGFß was measured in the serum samples by ELISA.


Determination of TGFß serum levels of the patients:

Without substantial variation, in all patients, the systemic TGFß level was enhanced within the first two weeks when compared to baseline; then the TGFß level declined prominently in patients with delayed union (p=0,002). After that the levels approached base line levels in all groups. The BMP-7 treated group showed the same serum levels as the union group.

Functional testing of serum of the patients:

In the same serum samples the functional activity was tested. Corresponding to the high TGFß serum levels the proliferation of the cells was reduced in the first and second week and approached normal levels. In patients with delayed fracture healing and BMP-7 treatment the effect was more pronounced and lasted longer.

Summary and conclusion:

  • In patients with non healing fractures, the TGFß serum levels are decreased.
  • BMP-7 restores the TGFß level in patients with non-healing fractures.
  • Serum of patients with non healing fractures treated with BMP-7 inhibits proliferation of a model tumor cell, compatible with the induction of cell differentiation

We conclude that the local application of BMP-7 induces the generation of TGFß which can be found systemically. Because of it´s proliferation and differentiation activities TGFß could participate in the restoration of fracture healing in patients with delayed union.