Adverse effect of botulinum toxin-A injections on mandibular bone: A systematic review and meta-analysis

Botulinum toxin-A (BTX) is a potent neurotoxin that is emerging in the scope of dental practice for its ability to temporarily paralyse musculature and reduce hyperfunction. This may be desirable in diseases/disorders associated with hyperactive muscles such as the muscles of mastication, most implicated in painful temporomandibular disorders (TMDs). The use of BTX extends beyond its indications with off-label use in TMD's and other conditions, while potential adverse effects remain understudied. BTX is well-established hindlimb paralysis model in animals leading to significant bone loss with underlying mechanisms remaining unclear. The objective of this study is to systematically review the literature for articles investigating changes in mandibular bone following BTX injections and meta-analyse available data on reported bone outcomes.

Comprehensive search of Medline, Embase and Web of Science retrieved 934 articles. Following the screening process, 36 articles in animals and humans were included for quantitative synthesis. Articles in human individuals (6) and three different animal species (14) presented mandibular bone outcomes that were included in the meta-analysis.

The masseter and temporalis muscles were frequently injected across all species. In humans, we observe a decrease of about 6% in cortical thickness of mandibular regions following BTX injection with no evident changes in either volume or density of bone structures. In animals, bone loss in the condylar region is significantly high in both cortical and trabecular compartments.

Our analysis supports the concept of BTX-induced bone-loss model in animal mandibles. Further, bone loss might be confined to the cortical compartments in humans. Most studies did not address the reality of repeated injections and excessive dosing, which occur due to the reversible action of BTX. More rigorous trials are needed to draw a full picture of potential long-term adverse effects on bone.