Pathways in external apical root resorption associated with orthodontia

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66 Scopus citations


To review studies investigating if genetic factors play a role in external apical root resorption (EARR) during orthodontic treatment. Heritability estimation in human sibpairs, comparison of multiple inbred mouse strains, human sib-pair linkage and parents-child trio association studies, and two gene (II-1b, and P2rx7) knock out mouse models. Heritability for EARR of the maxillary central incisors concurrent with orthodontic treatment is 0.8. DBA/2J, BALB/cJ, and 129P3/J inbred mouse strains are highly susceptible (p < .05) to histological root resorption (RR) associated with orthodontic force (RRAOF), whereas A J, C57BL 6J and SJL J mice are resistant. Non-parametric sibling pair linkage analysis identified evidence of linkage (LOD = 2.5; p = 0.02) of EARR with microsatellite D18S64 (tightly linked to TNFRSF11A, also known as RANK). There is significant linkage disequilibrium of IL-1B (p = 0.0003), and OPG (p = 0.003) with EARR. RRAOF increases in Il1b KO (p < 0.013), and increases in P2rx7 KO (p < 0.02) mice compared to wild-type. Genetic factors play a marked role in EARR concurrent with orthodontic force, accounting for one-half to two-thirds of the variation. Two pathways for this may involve: 1) activation control of osteoclasts through the ATP/P2XR7/IL-1B inflammation modulation pathway; and 2) RANK/RANKL/OPG osteoclast activation control. Histological RR occurs and is typically healed. If resorption outpaces healing, then EARR develops. Normal and parafunctional forces, as well as orthodontic forces, may add to or interact with the individual's susceptibility to pass the threshold of developing EARR.

Original languageEnglish
Pages (from-to)236-242
Number of pages7
JournalOrthodontics and Craniofacial Research
Issue number3
StatePublished - Aug 2009


  • Interleukin-1beta
  • Orthodontics
  • Osteoprotegerin
  • P2XR7
  • Root resorption

ASJC Scopus subject areas

  • Orthodontics
  • Surgery
  • Oral Surgery
  • Otorhinolaryngology


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