External apical root resorption during orthodontic treatment implicates specific molecular pathways that orchestrate nonphysiologic cellular activation. To date, a substantial number of in vitro and in vivo molecular, genomic, and proteomic studies have supplied data that provide new insights into root resorption. Recent mechanisms and developments reviewed here include the role of the cellular component—specifically, the balance of CD68⁺, iNOS⁺ M1- and CD68⁺, CD163⁺ M2-like macrophages associated with root resorption and root surface repair processes linked to the expression of the M1-associated proinflammatory cytokine tumor necrosis factor, inducible nitric oxide synthase, the M1 activator interferon γ, the M2 activator interleukin 4, and M2-associated anti-inflammatory interleukin 10 and arginase I. Insights into the role of mesenchymal dental pulp cells in attenuating dentin resorption in homeostasis are also reviewed. Data on recently deciphered molecular pathways are reviewed at the level of (1) clastic cell adhesion in the external apical root resorption process and the specific role of α/β integrins, osteopontin, and related extracellular matrix proteins; (2) clastic cell fusion and activation by the RANKL/RANK/OPG and ATP-P2RX7-IL1 pathways; and (3) regulatory mechanisms of root resorption repair by cementum at the proteomic and transcriptomic levels.

Objective: To determine whether orthodontic treatment with removable aligners vs fixed orthodontic appliances is associated with a different frequency of orthodontically induced external apical root resorption (OIEARR) when genetic, radiographic, and clinical factors are accounted for. Materials and Methods: Three hundred seventy-two orthodontic patients treated with removable aligners (Invisalign) or fixed appliances were genetically screened for interleukin 1B gene ( IL1B ) ( rs1143634 ), interleukin 1 receptor antagonist gene ( IL1RN ) ( rs419598 ), and osteopontin gene ( SPP1 ) ( rs9138/rs11730582 ). Twelve clinical variables, potentially associated with OIEARR, were also considered. Subjects were divided according to the presence of radiographically determined OIEARR (>2 mm). The association between OIEARR and appliance type, and radiographic, clinical and genetic factors, was assessed using backward stepwise conditional logistic regression. Odds ratios (ORs) and 95% confidence intervals (CIs) were reported. Results: Reliability of the methods was adequate. Clinical case complexity (American Board of Orthodontics [ABO] Discrepancy Index) (OR: 1.032; 95% CI: 1.005–1.061; P = .021) and extent of incisor apical displacement in the sagittal plane (OR: 1.478; 95% CI: 1.285–1.699; P = .001) were associated with an increased OIEARR risk. After adjusting for associations between clinical/radiographic/genetic factors, there were no statistically significant differences with respect to OIEARR or type of orthodontic appliance used, whether removable aligners or fixed appliances (OR: 1.662; 95% CI: 0.945–2.924; P = .078). Only subjects homozygous for the T allele of IL1RN ( rs419598 ) were more prone to OIEARR during orthodontic treatment (OR: 3.121; CI: 1.93–5.03; P < .001). Conclusions: A similar OIEARR predisposition was identified using either removable aligners (Invisalign) or fixed appliances.