For Doctors in a Hurry
- Researchers investigated whether onabotulinumtoxinA injections for masseter muscle prominence cause adverse changes to mandibular bone structure and morphology.
- This 12-month, placebo-controlled, Phase 2 study evaluated 187 healthy adults receiving up to 96 units of onabotulinumtoxinA.
- Quantitative assessments of 150 treated participants showed no significant differences in cortical thickness or bigonial width compared to placebo.
- The authors concluded that one or two treatments for masseter prominence produced no detectable morphometric changes over one year.
- Clinicians may consider these findings as evidence for the structural safety of masseter injections, though long-term effects remain unknown.
Structural Integrity of the Mandible Following Masseter Chemo-denervation
Masseter muscle prominence is a benign enlargement of the masticatory muscles that creates a widened or square lower facial contour, often prompting patients to seek aesthetic refinement [1, 2, 3]. While onabotulinumtoxinA effectively reduces muscle volume to achieve a more ovoid facial shape, its application in these high-force muscles has raised concerns regarding potential secondary skeletal changes [4, 5]. Specifically, clinicians have questioned whether the prolonged reduction in mechanical loading might trigger localized osteopenia (reduced bone mineral density) or alterations in mandibular morphology, such as changes in the gonial angle or cortical thickness [6, 7]. In a previous Phase 3 trial of 376 participants, a 72 U dose achieved a mean lower-facial width reduction of 5.24 mm compared to 0.04 mm in the placebo group (P <.0001) [4]. Because maintaining these results often requires repeat injections, understanding the cumulative impact on the mandibular condyle and ramus is essential for long-term safety [8]. New longitudinal data from a 12-month, placebo-controlled study now provides a detailed radiological assessment of these morphometric parameters following multiple treatment cycles [6, 7].
Trial Design and Multidetector CT Protocols
To evaluate the safety and morphometric impact of repeated masseter injections, researchers conducted a 12-month, double-blind, placebo-controlled, Phase 2 trial. The study population consisted of 187 healthy adults presenting with bilateral masseter muscle prominence. To assess the dose-response relationship and cumulative effects, the 150 participants in the active treatment arm received either one or two onabotulinumtoxinA treatments at varying dosages of 24, 48, 72, or 96 U. These patients were compared against a control group of 37 participants who received a placebo injection. This structured approach allowed clinicians to observe whether higher cumulative neurotoxin exposure influenced bone density or shape over a full year.
To achieve high-resolution visualization of the mandibular architecture, the study utilized multidetector computed tomography (MDCT), an advanced imaging technique that uses multiple rows of detectors to rapidly capture thin-slice, three-dimensional data of bone structures. This modality is particularly useful for detecting subtle changes in bone surface and density that might be missed by standard radiography. The longitudinal protocol required participants to undergo MDCT scans at baseline, day 90, and day 360. By tracking these specific time points, the researchers could monitor for both acute changes following the initial injection and late-emerging effects after a second treatment cycle. This rigorous imaging schedule was designed to identify any potential remodeling of the mandibular condyle, glenoid fossa, or articular eminence throughout the 12-month observation period.
Quantitative Stability Across Morphometric Parameters
To evaluate the structural impact of masseter chemo-denervation, the researchers employed a suite of quantitative assessments focused on the primary landmarks of the lower jaw. These measurements included bigonial width (the linear distance between the lower angles of the jaw) and cortical thickness (the density and depth of the outer bone layer). Additionally, the study tracked mandibular flare, which is the outward curvature of the jaw, and gonial angles, the angle formed by the junction of the lower border of the mandibular body and the posterior border of the ramus. These parameters are essential for clinicians to monitor, as they provide an objective baseline for detecting any potential bone resorption or remodeling that might occur when the mechanical load of the masseter muscle is reduced through neurotoxin injections.
The longitudinal analysis of these morphometric parameters revealed that quantitative assessments found no differences between the participants who received onabotulinumtoxinA and those in the control group. Specifically, the data compared the 150 participants in the active treatment arm against the 37 participants in the placebo group. Throughout the 12-month study period, which included up to two treatment cycles, the researchers observed no statistically significant changes in bigonial width, cortical thickness, mandibular flare, or gonial angles. For the practicing clinician, these findings suggest that the aesthetic reduction of masseter muscle volume does not translate to measurable alterations in the underlying mandibular bone structure within a one-year timeframe, offering reassurance when counseling patients on the structural safety of the procedure.
Qualitative Assessment of the Temporomandibular Complex
Beyond the linear measurements of the jaw, the researchers conducted a detailed qualitative analysis to ensure the structural integrity of the temporomandibular joint and its surrounding architecture. These qualitative assessments evaluated the mandibular condylar head, specifically examining its shape, position, cortical surface, and cortical thickness. The study also scrutinized the glenoid fossa (the depression in the temporal bone that articulates with the mandible) and the articular eminence (the bony prominence of the temporal bone that limits the forward movement of the condyle). For these structures, the investigators focused on their overall appearance and the integrity of the cortical surface to detect any subtle signs of bone remodeling or joint degradation.
The longitudinal data revealed that 94% of participants showed no qualitative changes to the mandibular condylar head, glenoid fossa, or articular eminence throughout the one-year study period. While the vast majority of the cohort remained stable, the researchers maintained a high threshold for safety by conducting further investigation into any radiographic anomalies. Specifically, repeated qualitative assessments were performed in 12 participants who initially presented with findings suggestive of post-baseline osteopathic change, a term referring to potential alterations in bone structure or density. Following this rigorous review, the authors determined that no clinically significant changes were identified in these 12 participants. For the practicing clinician, these results provide evidence that repeated onabotulinumtoxinA injections for masseter prominence do not appear to induce pathological changes in the critical articulating surfaces of the jaw, preserving normal joint mechanics.
Safety Profile and Clinical Considerations
Throughout the 12-month study period, the researchers maintained rigorous surveillance of adverse events to characterize the safety profile of repeated chemo-denervation in the masticatory space. The most frequently reported treatment-related adverse event was mastication disorder, which occurred in 6.0% of participants. This condition, which typically manifests as a temporary decrease in chewing force or efficiency, is a localized safety event entirely consistent with the known pharmacological mechanism of onabotulinumtoxinA in muscle tissue. These observed rates of mastication disorder align with prior reports following onabotulinumtoxinA masseter treatment for masseter muscle prominence, suggesting that the functional impact on the jaw remains predictable and limited to the targeted musculature.
Ultimately, the study concluded that the administration of 1 or 2 onabotulinumtoxinA treatments for masseter muscle prominence over a 1-year period resulted in no detectable differences in predefined mandibular morphometric measures when compared to placebo. While these multidetector computed tomography findings provide evidence of skeletal stability over a 12-month horizon, the researchers included a necessary caveat for long-term clinical management. Because bone remodeling is a gradual process influenced by chronic changes in mechanical loading, late-emerging effects beyond the 12-month study window cannot be excluded. This highlights the importance of continued clinical monitoring for patients receiving masseter injections over multiple years, ensuring that the lack of structural change observed in this trial persists over longer durations of treatment.
References
1. Liew S, Jones D, Dayan S, et al. A Controlled Phase 2b Trial to Assess the Efficacy and Safety of a Single Intervention of OnabotulinumtoxinA for Treating Masseter Muscle Prominence. Aesthetic Surgery Journal. 2025. doi:10.1093/asj/sjaf042
2. Carruthers J, Liew S, Rivers JK, et al. Reduction of masseter muscle prominence after treatment with onabotulinumtoxinA: Primary results from a randomized phase 2 study. Journal of the American Academy of Dermatology. 2024. doi:10.1016/j.jaad.2024.10.064
3. Liew S, Rivers JK, Humphrey S, et al. Improvement of Lower Facial Shape after Treatment with OnabotulinumtoxinA: Secondary Results from a Phase 2 Dose Escalation Study.. Plastic and reconstructive surgery. 2026. doi:10.1097/PRS.0000000000012345
4. Sun J, Wang L, Wu Y, et al. OnabotulinumtoxinA Treatment for Masseter Muscle Prominence: 6-Month Safety and Efficacy Results, Including Patient-Reported Outcomes, From a Phase 3, Randomized, Placebo-Controlled, Multiregional Trial. Aesthetic Surgery Journal. 2025. doi:10.1093/asj/sjaf204
5. Fabi S, Jones DK, Biesman B, et al. 34952 Efficacy and safety of 2 doses of onabotulinumtoxin A for the treatment of masseter muscle prominence: 6-month results from a randomized, phase 2b placebo-controlled study. Journal of American Academy of Dermatology. 2022. doi:10.1016/j.jaad.2022.06.676
6. Kostenuik PJ, Mallya SM, Hopfinger R, et al. Longitudinal Computed Tomography Indicates No Negative Impact of OnabotulinumtoxinA on Mandibular Bone Density in a 12-Month, Double-Blind, Randomized, Repeat Treatment, Placebo-Controlled Study in Healthy Adults With Masseter Muscle Prominence. Aesthetic Surgery Journal. 2025. doi:10.1093/asj/sjaf167
7. Mallya SM, Kostenuik P, Hopfinger R, et al. Longitudinal Computed Tomographic Evaluation of Mandibular Bone Morphology Following OnabotulinumtoxinA Treatment of Masseter Muscle Prominence: Results of a 12-Month, Repeat-Treatment, Placebo-Controlled Study in Healthy Adults.. Aesthetic surgery journal. 2026. doi:10.1093/asj/sjag080
8. Kassir M, Babaei M, Hasanzadeh S, Rezaei–Tavirani M, Razzaghi Z, Robati RM. Botulinium toxin applications in the lower face and neck: A comprehensive review. Journal of Cosmetic Dermatology. 2023. doi:10.1111/jocd.16116
