title: Use of new targeted cancer therapies in children: effects on dental development and risk of jaw osteonecrosis: a review.
abstract: New targeted cancer therapies such as bisphosphonates, denosumab, and bevacizumab are routinely used in adult for the past decades. Their introduction into pediatric medicine is more recent that means there is a paucity of data on long-term effects on dental development and on the risk of osteonecrosis of jaw. This study aimed to outline adverse effects of new targeted cancer therapies on oral cavity including dental abnormalities observed in pediatric population treated with these molecules and the risk of osteonecrosis of the jaw (ONJ). The impact of bisphosphonates and denosumab on bone remodeling (inhibition of osteoclasts) could interfere with teeth exfoliation and eruption processes, causing a tooth eruption delay. This hypothesis was confirmed, bisphosphonate-treated rats presented tooth eruption delay, and bisphosphonate therapy was associated with a mean delay of 1.67 years in tooth eruption in children with osteogenesis imperfecta. Another study showed that the inhibition of RANK/RANKL by denosumab was associated with a lack of tooth eruption in animals. Several animal studies reported that bisphosphonate could also induce dental abnormalities including defective amelogenesis and dentinogenesis in rats, but there is no evidence of such effects in children; only one case of enamel hypoplasia in a child treated for idiopathic arterial calcification with bisphosphate was reported. To date, there has been no reported case of ONJ in children treated with bisphosphonates, denosumab, or bevacizumab.
authors: Pediatric Dentistry Department, CHRU of Nancy, Vandoeuvre-les-Nancy, France.|Pediatric Dentistry Department, Faculty of Dentistry, Nancy, France.
authors: Magali
authors: M
authors: Hernandez
authors: Head and Neck Surgery and Dental Units, Oncology Surgery Department, Institute of Cancerology of Lorraine, Vandoeuvre-lès-Nancy, France.|Oral Surgery Department, Faculty of Dentistry, Nancy, France.
authors: Bérengère
authors: B
authors: Phulpin
authors: Pediatric Oncology Department, CHRU of Nancy, Vandoeuvre-les-Nancy, France.
authors: Ludovic
authors: L
authors: Mansuy
authors: Pediatric Dentistry Department, CHRU of Nancy, Vandoeuvre-les-Nancy, France.|Pediatric Dentistry Department, Faculty of Dentistry, Nancy, France.
authors: Dominique
authors: D
authors: Droz
mesh_terms: D000818:Animals; D000969:Antinematodal Agents / Q000009:adverse effects* / Q000627:therapeutic use; D000068258:Bevacizumab / Q000009:adverse effects / Q000627:therapeutic use; D059266:Bisphosphonate-Associated Osteonecrosis of the Jaw; D001859:Bone Neoplasms / Q000188:drug therapy*; D002648:Child; D000069448:Denosumab / Q000009:adverse effects / Q000627:therapeutic use; D004164:Diphosphonates / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D014070:Tooth / Q000187:drug effects / Q000254:growth & development*; D014078:Tooth Eruption / Q000187:drug effects
chemical_list: D000969:Antinematodal Agents; D004164:Diphosphonates; D000068258:Bevacizumab; D000069448:Denosumab
keywords: bevacizumab; bisphosphonates; buccal effects; children; denosumab