Free radical scavengers have a preventive effect on heterotopic bone formation following manipulation of immobilized rabbit legs.

AIM: The pathogenesis of heterotopic ossification (HO) is still unclear and the preventive measures and therapies are usually insufficient. The authors compared free radical scavengers with placebo in order to assess the magnitude of their inhibitory effect on the development of HO. METHODS: A standard immobilization-manipulation model was used to induce HO in the hind legs of twenty female New Zealand albino rabbits. The animals were divided into two groups and received daily either placebo or a free radical scavenger (A/A) cocktail in a randomized double-blind fashion. Every four days an X-ray was taken and the thickness and length of new bone formation were measured at the thigh by two investigators independently. RESULTS: Fisher's exact test revealed a significant difference in the development of heterotopic ossification between the placebo group and the A/A group (70% versus none, respectively ; P=0.0031). CONCLUSION: The ischemia/reperfusion syndrome could be an important precipitating factor in the pathogenesis of heterotopic ossification and free radical scavengers were found to have a significant inhibitory effect on its development in a rabbit model. The results of this experimental model can be an impetus for further research into the prevention of heterotopic bone formation in humans.

Free radical scavengers are more effective than indomethacin in the prevention of experimentally induced heterotopic ossification.

The pathogenesis of heterotopic ossification is still unclear and the preventive therapies are usually insufficient. The present study was designed to investigate the possible preventive effect of free radical scavengers on the development of experimentally induced heterotopic ossification in a rabbit model and to compare free radical scavengers with indomethacin to determine whether they act synergistically. A standard immobilization-manipulation model was used to induce heterotopic ossification in the hind legs of 40 1-year-old female New Zealand albino rabbits. The animals were divided into four groups and received daily either placebo, a free radical scavenger cocktail [allopurinol and N-acetylcysteine (A/A)], indomethacin or the combination of A/A and indomethacin in a randomized double-blind fashion. Every 4 days an X-ray was taken and the thickness and length of new bone formation was measured at the thigh. A marked statistically significant difference was found between the four groups. In the groups that received A/A, either alone or combined with indomethacin, an inhibition of bone growth, both in thickness and in length was demonstrated. In this experimental model free radical scavengers had a superior inhibitory effect on heterotopic ossification than indomethacin. Free radicals could play an important role in the pathogenesis of heterotopic ossification.