Use of Imatinib in the Prevention of Heterotopic Ossification

Abstract

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. 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. 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. The mean volume of heterotopic bone formed in the control group was 0.976mm(3) compared to 0.221mm(3) in the imatinib group. The volume of HO in the treatment group was reduced by 85% compared to the control group. 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. 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.