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

Abstract

IntroductionBotulinum 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.MethodsComprehensive 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.ResultsThe 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.DiscussionOur 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.

Efficacy of botulinum toxin type A in bruxism: a scoping review

“…As a way of complementing the evidence on effectiveness, it is up to dental surgeons to evaluate the application of TxBA for bruxism, as new evidence, such as that of Balanta-Melo et al, (2019) and Moussa et al, (2023), despite being fragile and initial, indicates that the substance is capable of leading to bone resorption in the head of the jaw.…”

Unilateral Hypofunction of the Masseter Leads to Molecular and 3D Morphometric Signs of Atrophy in Ipsilateral Agonist Masticatory Muscles in Adult Mice

“…Recently, a meta-analysis from a systematic review suggested that bone loss has been mainly evaluated in the mandibular condyle in animal studies. In contrast, human studies are focused on the mandibular ramus (where the masseter muscle is inserted) [41]. However, due to a low number of human studies and small size samples, combined with short-term follow-ups and the lack of dose standardization, there is a need for more clinical research to determine if these bone changes may negatively impact structures such as the temporomandibular joint, which is vital for physiological processes [40,41].…”

“…In contrast, human studies are focused on the mandibular ramus (where the masseter muscle is inserted) [41]. However, due to a low number of human studies and small size samples, combined with short-term follow-ups and the lack of dose standardization, there is a need for more clinical research to determine if these bone changes may negatively impact structures such as the temporomandibular joint, which is vital for physiological processes [40,41]. A clinical study demonstrated that using the BoNTA intervention to manage myofascial pain in adult women resulted in thickness reduction of the injected muscles (both masseter and temporalis), and reduced bone volume in the mandibular condyle in a dose-dependent manner; nonetheless, non-injected muscles were not assessed [42].…”

Exploring botulinum toxin’s impact on masseter hypertrophy: a randomized, triple-blinded clinical trial

“…Furthermore, the replacement of type IIa muscle fibers (anti-fatigue) for type IIb muscle fibers (non-anti-fatigue) and the replacement of contractile tissue with fat have also been observed in animal studies 14 – 16 . In addition, animal literature has found that these muscular alterations could worsen if we consider repeated injections of the treatment in masticatory muscles and as consequence lead to changes in mandibular bone which have been also demonstrated in clinical trials 18 – 20 .…”