A histomorphometric study of necrotic femoral head in rabbits treated with extracorporeal shock waves.

[Purpose] This study aimed to determine the effectiveness and mechanisms of extracorporeal shock wave therapy in the treatment of femoral head osteonecrosis. [Subjects and Methods] Histomorphometric analysis of necrotic femoral head in rabbits treated with shock waves was performed. Bilateral osteonecrosis of femoral heads was induced with methylprednisolone and lipopolysaccharide in eight rabbits. The left limb (study side) received shock waves to the femoral head. The right limb (control side) received no shock waves. Biopsies of the femoral heads were performed at 12 weeks after shock wave therapy. [Results] Necrotic femoral heads treated with shock waves, compared with controls, had higher bone volume per tissue volume, trabecular thickness, trabecular number, osteoblast surface/bone surface, osteoid surface/bone surface, osteoid thickness, mineralizing surface/bone surface, mineralizing apposition rate, and bone formation rate. However, trabecular separation was lower in shock wave-treated femoral heads than in controls. Eroded surface/bone surface and osteoclast surface/bone surface did not differ significantly between groups. [Conclusion] The bone mass of necrotic femoral heads treated with shock waves increases. Extracorporeal shock wave may promote bone repair in necrotic femoral heads through the proliferation and activation of osteoblasts.

Temporal and spatial expression of BMP-2 in sub-chondral bone of necrotic femoral heads in rabbits by use of extracorporeal shock waves.

BACKGROUND AND PURPOSE: Extracorporeal shock wave treatment has been used successfully for the treatment of avascular necrosis of the femoral head. The pathway of biological events by which this is accomplished has not been fully elucidated. BMP-2 is a key mediator of bone development and repair, and is uniquely required for bone formation. We therefore examined the effect of extracorporeal shock waves on induction of BMP-2 in necrotic femoral heads. METHODS: Femoral head necrosis was induced in rabbits by treatment with methylprednisolone and lipopolysaccharide. BMP-2 expression was assessed by immunohistochemistry, quantitative real-time PCR, and western blot analysis. Histomorphometric analysis was performed to evaluate the rate of bone formation in femoral heads treated with extracorporeal shock waves. RESULTS: Extracorporeal shock wave treatment was associated with a significant increase in expression of BMP-2 protein and mRNA in the subchondral bone of the necrotic femoral heads. Moreover, the most intensive immunostaining of BMP-2 was observed in the proliferative zone above the necrotic zone. Histomorphometric analysis showed that extracorporeal shock wave treatment significantly increased the rate of bone formation in the subchondral bone. INTERPRETATION: We conclude that extracorporeal shock wave treatment significantly upregulates the expression of BMP-2 in necrotic femoral heads. The process of repair of femoral head necrosis is accelerated by the use of extracorporeal shock waves.

Upregulation of VEGF in subchondral bone of necrotic femoral heads in rabbits with use of extracorporeal shock waves.

Extracorporeal shock wave treatment appears to be effective in patients with avascular necrosis of the femoral head. However, the pathway of biological events whereby this is accomplished has not been fully elucidated. The purpose of this study was to investigate the effect of extracorporeal shock waves on vascular endothelial growth factor (VEGF) expression in necrotic femoral heads of rabbits. VEGF expression was assessed by immunohistochemistry, quantitative real-time PCR, and Western blot analysis. The degree of angiogenesis was also assessed, as determined by the microvessel density (MVD), the assessment of which was based on CD31-expressing vessels. Bilateral avascular necrosis of femoral heads was induced with methylprednisolone and lipopolysaccharide in 30 New Zealand rabbits. The left limb (the study side) received shock wave therapy to the femoral head. The right limb (the control side) received no shock wave therapy. Biopsies of the femoral heads were performed at 1, 2, 4, 8, and 12 weeks. Western blot analysis and real-time PCR showed that shock wave therapy significantly increased VEGF protein and mRNA expression, respectively, in the subchondral bone of the treated necrotic femoral heads. Compared with the contralateral control without shock wave treatment, the VEGF mRNA expression levels increased to a peak at 2 weeks after the shock wave treatment and remained high for 8 weeks, then declined at 12 weeks, whereas the VEGF protein expression levels increased to a peak at 4 weeks after the shock wave treatment and remained high for 12 weeks. The immunostaining of VEGF was weak in the control group, and the immunoreactivity level in the shock-wave-treated group increased at 4 weeks and persisted for 12 weeks. The most intensive VEGF immunoreactivity was observed in the proliferative zone above the necrotic zone. At 4, 8, and 12 weeks after the shock wave treatment, MVD in subchondral bone from treated femoral heads was significantly higher than that in subchondral bone from untreated femoral heads. These data clearly show that extracorporeal shock waves can significantly upregulate the expression of VEGF. The upregulation of VEGF may play a role in inducing the ingrowth of neovascularization and in improving the blood supply to the femoral head.