Use of Imatinib in the Prevention of Heterotopic Ossification

Clément M. L. Werner, MD
Department of Traumatology, University Hospital, Zurich, Switzerland

Stefan M. Zimmermann, MD
Department of Traumatology, University Hospital, Zurich, Switzerland

Carola C. Würgler-Hauri, MD
Department of Traumatology, University Hospital, Zurich, Switzerland

Joseph M. Lane, MD
Attending Orthopaedic Surgeon, Hospital for Special Surgery
Professor of Orthopaedic Surgery, Weill Cornell Medical College

Guido A. Wanner, MD
Department of Traumatology, University Hospital, Zurich, Switzerland
Klinik fur Unfallchirurgie, UniversitatsSpital Surich, Switzerland

Hans-Peter Simmen, MD
Department of Traumatology, University Hospital, Zurich, Switzerland


Abstract

Background

Heterotopic ossification (HO) is a common complication following orthopedic and trauma surgery, which may have substantial negative effects on the postoperative outcome. Angiogenesis appears to play a critical role in heterotopic ossification. One of the involved signaling molecules is platelet-derived growth factor (PDGF) which may be inhibited by imatinib.

Questions/Purposes

Our goal was to prevent HO by pharmacologically interfering with the molecular signaling pathways involved in the developmental process. We hypothesized that by administering a proven inhibitor of PDGF expression, heterotopic bone formation may be prevented.

Methods

The effect of imatinib on HO formation was studied in a murine model which reliably produces islets of HO within the soft tissue following Achilles tenotomy. The control group underwent Achilles tenotomy only. The imatinib group received imatinib mesylate. After trial completion, the limbs were harvested and scanned by micro-CT. Heterotopic bone volume was then identified and quantified.

Results

The mean volume of heterotopic bone formed in the control group was 0.976mm3 compared to 0.221 mm3 in the imatinib group. The volume of HO in the treatment group was reduced by 85% compared to the control group.

Conclusions

The administration of imatinib was associated with a significantly reduced volume of HO. This may be due to the inhibitory effect of imatinib on the PDGF signaling pathway during development of HO.

Clinical Relevance

The successful reduction of HO formation following imatinib administration has led to further insight concerning the pathogenesis of HO which in the future may lead to new clinical approaches towards the prevention of HO.

This article appears in HSS Journal: Volume 9, Number 2.
View the full article at springerlink.com.

About the HSS Journal

HSS Journal, an academic peer-reviewed journal published three times a year, February, July and October. The Journal accepts and publishes peer reviewed articles from around the world that contribute to the advancement of the knowledge of musculoskeletal diseases and disorders.


^ Back to Top
Request an Appointment