Safety Outcomes and Related Tolerability and Biological Responses of Vibration-Assisted Orthodontic Tooth Movement: A Harm-Focused Systematic Review of RCTs.

Vibration-assisted orthodontic tooth movement (VA-OTM) has been promoted as an adjunct with the potential to accelerate treatment, yet its safety profile-together with related tolerability and biological responses-remains uncertain. This harm-focused systematic review of randomized controlled trials (RCTs) primarily appraised clinical safety end points of VA-OTM, while explicitly distinguishing these from tolerability/acceptability outcomes and biological response/surrogate markers. The protocol was prospectively registered in PROSPERO (CRD420251166672). Reporting followed the PRISMA-Harms extension and Cochrane guidance for harms. Major databases and gray literature were searched through August 2025 without restrictions. Eligible RCTs compared intraoral vibration with no adjunct or sham during fixed-appliance or clear-aligner therapy. Outcome-level risk of bias was assessed using RoB 2 and certainty of evidence with Grading of Recommendations Assessment, Development, and Evaluation (GRADE); heterogeneity precluded meta-analysis, so synthesis was narrative. Twenty-three RCTs (902 participants) were included. For clinical safety end points, root resorption during canine retraction, including severe resorption (>2 mm), was similar between groups, although one of two premolar tipping studies reported smaller resorption crater volumes with vibration (p = 0.003). Periodontal indices and tooth mobility generally did not differ between groups (p > 0.05). For tolerability/acceptability outcomes, vibration did not consistently reduce pain. During fixed-appliance alignment, one RCT reported lower pain scores with vibration (~1.0-2.3/10 vs. 4.5-6.8/10; p < 0.001), whereas four RCTs showed no significant difference (p > 0.05). In clear-aligner therapy, two RCTs showed early reductions in pain (p < 0.05; p = 0.006) and two did not (p > 0.05). Oral health-related quality of life and analgesic use showed no clear benefit (p > 0.05). Biomarker findings were inconsistent: four RCTs reported higher IL-1β and/or PGE2 levels with vibration (p = 0.001, p < 0.05, p ≤ 0.03, and p < 0.001), whereas three found no meaningful change. Most outcome-level RoB 2 judgments raised some concerns (about 89%), and the certainty of evidence was low to very low for most outcomes. Within these limitations and short follow-up, adjunctive low-intensity intraoral vibration appears unlikely to compromise root integrity, periodontal health, or tooth stability, but does not justify routine use primarily for pain control, quality-of-life improvement, or root-resorption prevention; larger, long-term harm-focused RCTs with standardized safety outcomes are needed before extrapolating findings to untested devices or dosing regimens.