Background: This longitudinal prospective study aimed to assess orthodontic patients’ immune system response to metal ion release in saliva. Methods: Thirty adult patients (18–35 years) were equally divided into three groups: groups at the end (G1) and beginning (G2) of multibracket appliances (MBA) treatment and a non-treated control group (G3). Participants were evaluated at four timepoints within 21 days, with saliva samples being analyzed for metal ion concentrations and blood for the lymphocyte transformation test (LTT). Results: There were no significant differences between groups or timepoints for saliva. LTT analyses revealed hypersensitivity in one-third of all patients and 50% of G2 for nickel, with three developing sensitizations after MBA insertion. All nickel-sensitized patients exhibited varying elevated saliva nickel concentrations. The most nickel-sensitized patients had low ion saliva loads. In borderline nickel-sensitization cases, saliva ion concentrations were up to 20 times higher than the reference. Hypersensitivity to palladium, gold, and mercury was also observed. Conclusions: These findings indicate that increased MBA ion release was not inherently linked to the immune response (Type-IV sensitization), as reactions occurred even with ion levels below thresholds. This underlines the need for a comprehensive evaluation of the immune response to metal ion release in orthodontic patients.

Objective: The aim of this systematic review was to evaluate the skeletal and dental effects of skeletally‐anchored (SA) maxillary protraction compared with conventional facemask (FM) therapy in growing patients with Class III malocclusion, while controlling for the confounding effect of rapid maxillary expansion (RME). Materials and Methods: A systematic literature search (MEDLINE, Cochrane Library, Virtual Health Library, Web of Science, Google Scholar), which involved two screening stages, was performed until January 2026 and identified prospective clinical trials comparing SA with conventional tooth‐borne FM therapy. Only studies in which expansion protocols were applied uniformly across groups were included. Risk of bias was assessed with RoB 2 and ROBINS‐I tools, and random effects meta‐analyses were conducted for cephalometric outcomes. The certainty of the evidence was evaluated according to the grading of recommendations, assessment, development, and evaluation (GRADE) approach. Results: Five prospective trials (3 RCTs, 2 CCTs; n = 194 participants) met the inclusion criteria. Random‐effects meta‐analyses showed a modest but significant greater increase in SNA for SA (MD 0.65°; 95% CI 0.18–1.13, I ² = 0.0%) and consistently fewer dental side effects with SA: upper‐molar mesialization (−1.14 mm; −2.12 to −0.17, I ² = 10.3%), molar extrusion (−0.74 mm; −1.07 to −0.40, I ² = 0.0%), and maxillary incisor proclination (−2.47°; −4.14 to −0.80, I ² = 0.0%). The mandibular plane rotation did not differ significantly (−0.38°; −1.67 to 0.91, I ² = 45.6%). Risk of bias was assessed as “some concerns” in RCTs and “serious” in non‐randomized studies. The certainty of evidence ranged from very low to moderate according to GRADE. Conclusions: Within the limitations of the available short‐term evidence, and given the low‐to‐moderate certainty of the pooled estimates, SA was associated with fewer dental side effects and a statistically significant, though not clinically relevant, gain in skeletal efficacy. Future long‐term, age‐stratified randomized trials are needed to confirm the long‐term stability of these findings.