ICCBH2013 Poster Presentations (1) (201 abstracts)
Craniofacial consequences of high dose zoledronic acid injections in onco-pediatric patients
Frederic Lezot 1 , Julie Chesneau 1 , Severine Battaglia 1 , Regis Brion 1 , Jean-Christophe Farges 2 , Dominique Heymann 1 & Francoise Redini 1
1INSERM UMR 957 – Université de Nantes EA 3822, Nantes, France; 2IGFL, CNRS UMR-5242, ENS de Lyon, Lyon, France.
Background: High doses of zoledronic acid (ZOL), one of the most potent inhibitors of bone resorption; is currently evaluated in a phase III clinical trial in Europe for the treatment of malignant pediatric primary bone tumors. The impact of such an intensive treatment on the craniofacial skeleton is a critical question in the context of patients with actively growing skeleton; in particular in the light of our previous studies evidencing that endochondral bone formation was transiently disturbed by high doses of ZOL.
Methods: Two protocols adapted from pediatric treatments were developed for newborn mice (A total of five or ten injections of ZOL 50 μg/kg every 2 days). Their impact on skull bones and teeth growth was analyzed by microCT and histology up to 3 months after the last injection.
Results: ZOL administrations induced a transient delay of skull bone growth and an irreversible delay in incisor and first molar eruption and root elongation. Other teeth eruption was affected, but most were erupted by 3 months. All molars root histogenesis was severely impacted and massive odontogenic tumor-like structures were observed in all mandibular incisors.
Conclusion: High doses of ZOL irreversibly disturbed teeth eruption and elongation, and delayed skull bone formation. These preclinical observations are essential for the follow-up of onco-pediatric patients treated with ZOL.
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