Effects of prophylactic tadalafil use in a rabbit model of femoral head osteonecrosis

Introduction: Femoral head osteonecrosis secondary to high dose steroid use for childhood malignancies or rheumatological diseases in the pediatric and adolescent population is a serious problem. Currently, there are no evidence-based prophylactic methods in the literature for these patients. Phosphodiesterase inhibitors have the potential to be used in prophylaxis and treatment due to their mechanism of action. We aimed to assess the radiological, histopathological, and molecular biologic effects of prophylactic tadalafil use in a rabbit femoral osteonecrosis model using high dose corticosteroids and lipopolysaccharide. Material and method: 24 New Zealand rabbits were divided into three equal groups. 8 were designated as the control group (G0) and no further intervention was made. Rabbits in group 1 (G1) received 0.1 mg/kg E. coli lipopolysaccharide (LPS) intravenously. Then starting on the same day, 40 mg/kg methylprednisolone sodium succinate (MP) was given intramuscularly (IM) for three days consecutively. Rabbits in group 2 (G2) were given 5 mg/kg tadalafil orally for ten consecutive days. Starting on the eighth day, 0.1 mg/kg LPS was given followed by three days of 40 mg/kg MP injections as in rabbits in G1. All animals were sacrificed 3 weeks after the final MP injection. Magnetic resonance imaging (MRI) was performed and bilateral femora were harvested. Halves of the femoral heads were saved for VEGF examination with Western blot analysis. The remaining parts were examined histopathologically for the presence of osteonecrosis. Results: In G1, 15 out of 16 hips (93%) of 8 rabbits had osteonecrosis compared to 8 out of 12 hips (67%) of 6 rabbits in G2 (p>0.05). VEGF expression in G2 was significantly higher than G0 and G1 (p<0.05 and p<0.0004, respectively). VEGF expression was not significantly different between G0 and G1. Conclusions: Lipopolysaccharide and corticosteroid combination achieved a very high rate of osteonecrosis in the rabbits. Prophylactic tadalafil use did not decrease the occurrence of osteonecrosis significantly. On the other hand, it increased VEGF expression in the femoral head significantly, independent from the effects of steroids and lipopolysaccharide. Keywords: steroid-induced osteonecrosis, prophylaxis, rabbit osteonecrosis model, lipopolysaccharide, vascular endothelial growth factor, phosphodiesterase inhibitors, tadalafil