Early apoptosis predicts orthodontically induced root resorption: inhibitory effects of lithium in a rat model

Mechanical compression of the periodontal ligament (PDL) is a key trigger of orthodontically induced root resorption (OIRR). Although PDL compression during the early phase of orthodontic force application correlates strongly with OIRR severity, associated cellular events remain insufficiently defined. This study aimed at elucidating mechanisms underlying the initiation of OIRR, focusing on PDL compression and associated cellular responses, and identifying cellular targets through which lithium exerts inhibitory effects.

Thirty-seven 10-week-old male Wistar rats were assigned to lithium-treated and saline groups. Daily intraperitoneal injections were administered, and a 25 cN mesial orthodontic force was applied to the maxillary first molar for 14 days. PDL thickness was evaluated using microcomputed tomography. Histological analyses quantified the OIRR area, apoptotic cell count, and odontoclast number.

In both groups, early PDL compression ratios showed strong positive correlations with OIRR area and early apoptotic cell counts. Lithium significantly reduced OIRR but did not alter PDL compression compared with saline. At comparable PDL compression ratios, the lithium group exhibited consistently smaller OIRR areas and fewer early apoptotic cells. The early odontoclast numbers remained low and showed no intergroup differences. These findings suggest that the protective effect of lithium was primarily mediated by the suppression of early apoptosis, cellular response to PDL compression.

Early PDL compression and apoptosis play pivotal roles in OIRR initiation and are potential predictive markers. Lithium attenuated OIRR by suppressing early apoptosis without altering PDL compression, highlighting early apoptosis as a promising therapeutic target for OIRR prevention.