Effects of high dose of zoledronic acid on superficial vascular network of membranous bone sites: an intravital study on rat calvarium.

Abstract

We evaluated the impact of high dose of zoledronic acid on the superficial vascular network parameters of a membranous bone site. During a 5-day follow-up, significant reduction of the vascular density is observed only in the treated group. The superficial vascularization is of great importance in membranous bone-healing process. A new rat calvarium intravital model was developed to study the short-term effect of a single high dose of zoledronic acid infusion on the superficial vascularization. Optical bone chambers were implanted in the bone tissue surface of Sprague-Dawley rats' calvarium. Nine rats were injected i.v. with 400 µg/kg of zoledronic acid (Z group), and nine rats were injected with vehicle (PSS group). A 5-day follow-up of the vascular network was made by the use of pictures analysis method. The vascular density significantly decreases only in Z group but there was no significant difference between groups at individual time points. The total length of the vascular network decreases significantly in Z group only (p=0.003) with a significant higher decrease at D3 (p=0.04) and D5 (p=0.02) compared with control. The vascular density related to the smaller vessels (width, 5-10 µm) decreases significantly between T0 and D5 in Z group only (p=0.002). With the help of an original intravital animal model a significant modifications on the total length of the vascular network and the vascular density of small vessels are highlighted on a membranous bone site.