Echinomycin did not affect the safety of fracture healing: an experimental pilot study on a murine femur fracture model.

Thorsten Jentzsch,Hans-Peter Simmen,Flora Nicholls,Stefan M Zimmermann,Paolo Cinelli,Clément M L Werner

doi:10.1186/s13037-016-0094-9

Thorsten Jentzsch, Hans-Peter Simmen + Show 4 more

Open Access

https://doi.org/10.1186/s13037-016-0094-9

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Abstract

BackgroundThere is a need for effective drugs in the prevention and treatment of heterotopic ossifications (HO) after fractures. Echinomycin has been shown to prevent formation of HO in an animal model. However, before it may be considered as an option against HO, it needs to be studied whether it prevents fracture healing similar to non-steroidal anti-inflammatory drugs (NSAIDS). Therefore, the hypothesis was that echinomycin prevents fracture healing and callus formation.MethodsIn an experimental murine pilot study, standard blunt femur fractures were induced and retrograde intramedullary compression fixation of the femur was performed. The treatment group (n = 8) received echinomycin (0.3 mg/kg body weight) and the control group (n = 8) did not receive echinomycin. The fractures and implant positions were verified by conventional X-rays immediately postoperatively. As the primary outcome variable, fracture healing (osseous consolidation) was evaluated by conventional X-rays and micro-computed tomography (CT) scans after ten weeks and graded as healed, partial or complete pseudarthrosis. The secondary outcome, callus formation, was graded semi-quantitatively from 0 (mostly absent) to 3 (maximum).ResultsFracture healing was present in all living cases after ten weeks concerning the treatment group. Partial pseudarthrosis was seen in two cases, one in the treatment and another one in the control group. Complete pseudarthrosis was seen in one case of the control group after an open fracture. Callus formation was similar in both groups with a mean grade of 1.5 within each group. Two cases of the treatment group died.ConclusionAs a novel finding, echinomycin did not inhibit fracture healing or callus formation in this in vivo murine standard femur fracture model pilot study. Further studies involving a larger number of cases, quantitative assessment with CT scans and histopathological analysis are needed before generalizing the results of this pilot study.

Highlights

There is a need for effective drugs in the prevention and treatment of heterotopic ossifications (HO) after fractures
Partial pseudarthrosis was seen in two cases: one (12.5 %) in the treatment and another one (12.5 %) in the control group
Using micro-computed tomography (CT), some callus formation was visible in all (100 %) cases alive after 10 weeks indicating that the femoral fracture model resulted in an actual fracture in every (100 %) case. This pilot study represents the first investigation about the effects of echinomycin on fracture healing and callus formation

Summary

Introduction

There is a need for effective drugs in the prevention and treatment of heterotopic ossifications (HO) after fractures. Echinomycin has been shown to prevent formation of HO in an animal model. Before it may be considered as an option against HO, it needs to be studied whether it prevents fracture healing similar to non-steroidal anti-inflammatory drugs (NSAIDS). The hypothesis was that echinomycin prevents fracture healing and callus formation. Hypoxic stress may activate the deoxyribonucleic acid(DNA-)binding activity of hypoxia-inducible factors (HIF) [4] This may induce angiogenic stimulators, leading to the activation of vascular endothelial growth factor (VEGF) [5] and osteoprogenitor cells [6]. In comparison to normal callus formation, these events lead to the deposition of calcium and formation of HO [7]

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