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

Osteoporos Int. 2010 Nov;21(11):1919-25. doi: 10.1007/s00198-009-1146-0. Epub 2009 Dec 18.

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.

Introduction: 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.

Methods: 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.

Results: 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).

Conclusions: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Vessels / anatomy & histology
  • Blood Vessels / drug effects
  • Bone Density Conservation Agents / pharmacology*
  • Diffusion Chambers, Culture
  • Diphosphonates / pharmacology*
  • Drug Evaluation, Preclinical / methods
  • Image Processing, Computer-Assisted / methods
  • Imidazoles / pharmacology*
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Skull / blood supply*
  • Skull / drug effects
  • Skull / physiology
  • Wound Healing / drug effects
  • Wound Healing / physiology
  • Zoledronic Acid

Substances

  • Bone Density Conservation Agents
  • Diphosphonates
  • Imidazoles
  • Zoledronic Acid