Immune Changes Induced by Orthodontic Forces: A Critical Review

Orthodontic tooth movement (OTM) is generated by a mechanical force that induces an aseptic inflammatory response in the periodontal tissues and a subsequent coordinated process of bone resorption and apposition. In this review, we critically summarize the current knowledge on the immune processes involved in OTM inflammation and provide a novel insight into the relationship between classical inflammation and clinical OTM phases. We found that most studies focused on the acute inflammatory process, which ignites the initial alveolar bone resorption. However, the exact mechanisms and the immune reactions involved in the following OTM phases remain obscure. Recent studies highlight the existence of a typical innate response of resident and extravasated immune cells, including granulocytes and natural killer (NK), dendritic, and gamma delta T cells. Based on few available studies, we shed light on an active, albeit incomplete, process of resolution in the lag phase, supported by continuously elevated ratios of M1/M2 macrophage and receptor activator of nuclear factor kappa B ligand/osteoprotegerin ratio. This partial resolution enables tissue formation and creates the appropriate environment for a transition between the innate and adaptive arms of the immune system, essential for the tissue's return to homeostasis. Nevertheless, as the mechanical trigger persists, the resolution turns into a low-grade chronic inflammation, which underlies the next, acceleration/linear OTM phase. In this stage, the acute inflammation dampens, and a simultaneous process of bone resorption and formation occurs, driven by B and T cells of the adaptive immune arm. Excessive orthodontic forces or tooth movement in periodontally affected inflamed tissues may hamper resolution, leading to "maladaptive homeostasis" and tissue loss due to uncoupled bone resorption and formation. The review ends with a brief description of the translational studies on OTM immunomodulation. Future studies are necessary for further uncovering cellular and molecular immune targets and developing novel strategies for controlling OTM by local and sustained tuning of the inflammatory process.