Vascular Alterations in the Sprague-Dawley Rat Mandible During Intravenous Bisphosphonate Therapy
Long-term use of intravenous bisphosphonates, such as zoledronic acid (zoledronate), has been linked to bisphosphonate-related osteonecrosis of the jaw (BRONJ). Invasive dental surgery seems to trigger the bone necrosis in most cases. To determine the effects of zoledronic acid on the vascular structure of the rat mandible. Extracted of the mandibular first molar in rats that received 2 IV injections of zoledronate (20 μg/kg), 4 weeks apart. Zoledronate-treated rats (n = 18) were then compared to a control group of untreated rats (n = 18). At the fourth, eighth, and 12th week after molar extraction, 8 rat mandibles from each group were perfused with 35% radiopaque triphenylbismuth in methyl methacrylate via carotid artery perfusion. Mandibles were harvested and examined by micro-CT to assess the spatial and dimensional changes of the vasculature as a result of zoledronate treatment. The micro-CT analysis showed that zoledronic acid-treated rats had blood vessels that were thicker, less connected, and less ordered than control rats that were not exposed to zoledronic acid. This study demonstrated that treatment with zoledronic acid in rats is associated with vascular changes in alveolar bone. Further studies are underway to explore whether these vascular changes contribute to the pathogenesis of BRONJ.
Figure 1. Lateral (a) and medial (b) view of a decalcified right hemi-mandible. The bluish dye of the contrast material can be seen. Figure 2. Reconstructed micro-CT images from representative control (a) and zoledronic acid-treated (b) decalcified right hemimandibles after perfusion with methyl methacrylate containing triphenylbismuth. Vascular perfusion is diminished in the zoledronic acid-treated animals.
Micro-CT of an undecalcified right hemi-mandible taken from the initial pilot studies. The anterior region of interest, depicted by the red circle, was localized to the area of the first molar extraction socket while the posterior region of interest, depicted by the yellow circle, was localized to the area posterior to the extraction site.
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