ECTS2013 Poster Presentations Paediatric bone disease (7 abstracts)
Craniofacial consequences of high-dose zoledronic acid injections in onco-pediatric patients
Frédéric Lezot 1, , Julie Chesneau 1, , Séverine Battaglia 1, , Régis Brion 1, , Jean-Christophe Farges 3 , Géraldine Lescaille 4 , Beatriz Castaneda 4 , Perrine Marec-Berard 5 , Laurence Brugieres 6 , Nadège Corradini 7 , Dominique Heymann 1, & Françoise Redini 1,
1INSERM UMR957, Nantes, France; 2UNAM Université de Nantes, Nantes, France; 3IGFL, CNRS UMR5242, Lyon, France; 4Service Odontologie, Hôpital Pitié Salpétrière, Paris, France; 5Insitut d’Hémato-Oncologie Pédiatrique, Lyon, France; 6Département de Pédiatrie, Villejuif, France; 7Servoce d’Hémato-Oncologie Pédiatrique, Nantes, France.
Background: High zoledronic acid (ZOL) dose protocol, 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 growth is a critical question in the context of patients with actively growing skeleton, 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 10 injections of ZOL 50 μg/kg every 2 days). Their impact on skull bones and teeth growth was analyzed by micro computed tomography and histology up to 3 months after the last injection. In parallel, radiographies of patients from the French OS2006 protocol were analyzed for potential orofacial consequences.
Results: In mouse, ZOL administrations induced a transient delay of skull bone growth and an irreversible delay in incisor, first molar eruption, and root elongation. Other teeth were affected, but most were erupted by 3 months. Root histogenesis was severely impacted for all molars and massive odontogenic tumor-like structures were observed in all mandibular incisors. In younger pediatric patients a significant delay of tooth eruption was observed.
Conclusion: In mouse, high doses of ZOL irreversibly disturbed teeth eruption and elongation, and delayed skull bone formation. In human, the same treatment may impact the permanent teeth eruption. These preclinical and clinical observations are essential for the follow-up of onco-pediatric patients treated with ZOL.
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Bone Abstracts
ISSN 2052-1219 (online)
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