BACKGROUND: Vascular calcification is an active process, sharing common molecular mechanisms with bone formation. Bisphosphonates are components, which inhibit calcification. The aim of the present study was to evaluate the safety and effectiveness of local delivery of the bisphosphonate zoledronate on inhibition of calcium formation in the arterial wall in an experimental animal model. METHODS: Sixteen New Zealand rabbits were placed on vitamin D enriched atherogenic diet for 3 weeks. Subsequently, all animals underwent angiography of abdominal aorta and common iliac arteries. A mixture containing 500 μg/l zoledronate was delivered on the vascular wall of the target iliac artery, using a dedicated balloon catheter. A placebo mixture was administered on the contralateral iliac artery of each animal, which was used as control. At 28 days all animals were sacrificed. Histologic sections of each common iliac artery were stained with hematoxylin-eosin and von Kossa. Computer-assisted histomorphometry was performed for the calcium content quantification of each section from the target and the control iliac artery. RESULTS: In all animals the local delivery of zoledronate and placebo mixtures was successful and uncomplicated. The mean percentage of the calcium content of the media was higher in the control artery segments compared to the target (2.66 ± 0.73 versus 1.08 ± 0.62 % of the area of the media, p<0.01). CONCLUSIONS: Inhibition of vascular calcification by local catheter-based delivery of bisphosphonate zolendronic acid is effective without evident short-term complications. These finding and its potential clinical implication remain to be confirmed in human studies.
BACKGROUND:Vascular calcification is an active process, sharing common molecular mechanisms with bone formation. Bisphosphonates are components, which inhibit calcification. The aim of the present study was to evaluate the safety and effectiveness of local delivery of the bisphosphonatezoledronate on inhibition of calcium formation in the arterial wall in an experimental animal model. METHODS: Sixteen New Zealand rabbits were placed on vitamin D enriched atherogenic diet for 3 weeks. Subsequently, all animals underwent angiography of abdominal aorta and common iliac arteries. A mixture containing 500 μg/l zoledronate was delivered on the vascular wall of the target iliac artery, using a dedicated balloon catheter. A placebo mixture was administered on the contralateral iliac artery of each animal, which was used as control. At 28 days all animals were sacrificed. Histologic sections of each common iliac artery were stained with hematoxylin-eosin and von Kossa. Computer-assisted histomorphometry was performed for the calcium content quantification of each section from the target and the control iliac artery. RESULTS: In all animals the local delivery of zoledronate and placebo mixtures was successful and uncomplicated. The mean percentage of the calcium content of the media was higher in the control artery segments compared to the target (2.66 ± 0.73 versus 1.08 ± 0.62 % of the area of the media, p<0.01). CONCLUSIONS: Inhibition of vascular calcification by local catheter-based delivery of bisphosphonatezolendronic acid is effective without evident short-term complications. These finding and its potential clinical implication remain to be confirmed in human studies.