gms | German Medical Science

127. Kongress der Deutschen Gesellschaft für Chirurgie

Deutsche Gesellschaft für Chirurgie

20.04. - 23.04.2010, Berlin

Heterotopic Ossification – new approaches

Meeting Abstract

  • Clement Werner - Universitätsspital Zürich, Unfallchirurgie, Zürich, Schweiz
  • Carola Würgler-Hauri - Unfallchirurgie, Unfallchirurgie, Zürich, Schweiz
  • Stefan Zimmermann - Unfallchirurgie, Unfallchirurgie, Zürich, Schweiz
  • Guido Wanner - Universitätsspital Zürich, Unfallchirurgie, Zürich, Schweiz
  • Hans-Peter Simmen - Universitätsspital Zürich, Unfallchirurgie, Zürich, Schweiz

Deutsche Gesellschaft für Chirurgie. 127. Kongress der Deutschen Gesellschaft für Chirurgie. Berlin, 20.-23.04.2010. Düsseldorf: German Medical Science GMS Publishing House; 2010. Doc10dgch588

doi: 10.3205/10dgch588, urn:nbn:de:0183-10dgch5884

Veröffentlicht: 17. Mai 2010

© 2010 Werner et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen ( Er darf vervielfältigt, verbreitet und öffentlich zugänglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.



Introduction: Heterotopic ossification of soft tissue is a significantly disabling problem in orthopaedic surgery. Severe joint contracture, ankylosis, spasticity, neurovascular compression, pressure ulcers leading to significant disability may be due to heterotopic ossification.

Therapeutical options include NSAID's and local radiation as well as bisphosphonates, all of which inherently carry major disadvantages such as delayed fracture healing and impairing ossification.

Hypoxia reportedly stimulates the secretion of HIF-1α. This leads to an increased VEGF production, which acts as a main stimulus for angiogenesis and formation of heterotopic ossification. The inhibition of this pathway could be an essential therapeutical approach. Echinomycin as an antibiotic agent allegedly inhibits the production of VEGF. Therefore we used an established animal model and examined the heterotopic ossification after treatment with Echinomycin.

Materials and methods: Male CD-1 mice (n=20) were used in this study as approved by the relevant Swiss authorities. All mice underwent bilateral Achilles tendon tenotomy and were divided into groups: Control (n=10), Echinomycin (n=10). The control group underwent Achilles tenotomy only. The Echinomycin group received 10 mcg Echinomycin subcutaneously for 4 weeks, followed by 6 weeks of rest and cage activity only. After 10 weeks the limbs were harvested and Micro CT was performed with a nominal resolution of 30micrometers. Heterotopic bone volume was then identified in 3d images. Statistical analysis was performed using the Wilcoxon rank sum test.

Results: In 12% of the samples no heterotopic ossifications were found. In all other samples, heterotopic ossifications with a bone volume ranging from 0.000–1.649 mm3 were found. The mean bone volume in the control group was 0.976 mm3 whereas the mean bone volume in the Echinomycin group was 0.092 mm3. Range: 0.00–0.488 mm3 (p 0.003).

(Figure 1 [Fig. 1])

Conclusion: A significant reduction in bone volume (roughly 90%) could be observed in the group treated with Echinomycin (p=0.003). Although a significant decrease in bone volume could be achieved, it was not possible to completely prevent the occurrence of heterotopic ossification. Further trials will be done to investigate the clinically disabling problem of heterotopic ossification and its treatment.