Literature Review: Bone Effects of Botulinum Toxin Injection to the Masseter Muscle

Introduction:

Botulinum toxin (BTX), a neurotoxic protein derived from Clostridium botulinum, functions by inhibiting the release of acetylcholine at the neuromuscular junction, leading to temporary muscle paralysis [1]. In recent years, BTX has found widespread use in aesthetic medicine, dentistry, and pain management, with a prominent application being the injection into the masseter muscle [1]. The masseter muscle plays a crucial role in jaw movement, and BTX is commonly used for treating conditions such as bruxism (teeth grinding), temporomandibular joint (TMJ) disorders, and for cosmetic purposes such as jaw slimming [2]. 

While the effects of BTX on the masseter muscle are well-documented, there is an increasing interest in exploring its potential impact on bone tissue, particularly in the mandible [3]. Changes in muscle activity following BTX injection could influence mechanical forces applied to bone, which in turn may affect bone remodeling and overall bone health [3]. This review aims to examine current research on the bone effects of BTX injections into the masseter, focusing on bone remodeling, bone density, and changes in mandibular morphology. 

Methodology 

To compile this review, a systematic search was conducted using databases such as PubMed, Google Scholar, and research gate. The search strategy included terms such as "Botulinum toxin masseter bone effects", "Botulinum toxin jawbone remodeling", "masseter muscle bone changes," and "Botulinum toxin impact on bone health". Only peer-reviewed studies published within the last 15 years were considered, with a focus on studies directly or indirectly examining the bone effects of Botulinum toxin in relation to the masseter muscle. 

Body of the Review 

Botulinum Toxin and Muscle-Bone Interactions 

The masseter muscle plays a key role in generating the mechanical forces required for chewing and other oral functions [2]. These forces are transmitted to the mandible, where they stimulate bone remodeling processes, helping to maintain bone density and strength [3,4]. When BTX is injected into the masseter, it reduces muscle activity and alters these mechanical forces [1,3,4]. This reduction in mechanical loading may have consequences for the bone, potentially affecting both the structure and density of the mandible [1,3,4]. 

Mechanism of Action of Botulinum Toxin 

Botulinum toxin works by inhibiting the release of acetylcholine at the neuromuscular junction, leading to a temporary paralysis of the injected muscle [1]. In the case of the masseter, this results in reduced contraction forces, which in turn decreases the mechanical stress exerted on the mandible [4]. Several animal studies have demonstrated significant bone loss in regions such as the mandibular condyle and alveolar bone following BTX injections into masticatory muscles [4]. These changes raise concerns about an increased risk of fractures, especially in patients receiving repeated BTX injections over time [4]. However, human studies investigating mandibular bone changes following BTX injection remain limited, though some evidence suggests that BTX can impact condylar bone density and volume [4]. 

Bone Remodeling and biomechanical signaling 

Bone remodeling is a continuous process involving the resorption of old bone and the formation of new bone [3]. Mechanical forces exerted by muscles during movement or activity stimulate osteocytes, which in turn signal osteoblasts and osteoclasts to regulate bone formation and resorption [3]. The absence or reduction of mechanical forces, as seen with BTX injections into the masseter, could disrupt this process [3]. Studies in animals have shown that BTX injection into the masticatory muscles leads to decreased cortical thickness and density in the temporomandibular joint (TMJ) condyles, which are key load-bearing regions of the mandible [3]. These findings suggest that BTX-induced muscle paralysis may influence bone metabolism by reducing mechanical loading, thus impairing normal bone turnover [3]. 

Clinical Observations of Bone Effects 

Several studies have explored the potential impact of Botox on bone, with a particular focus on the mandible and surrounding structures. While the research in humans is still developing, there is emerging evidence that BTX injections into the masseter muscle can affect mandibular bone morphology and density [5]. The observed changes include alterations in bone volume and shape, which may be linked to muscle atrophy and reduced mechanical stress on the bone [2,5]. 

Changes in Mandibular Bone Morphology 

Several studies have documented morphological changes in the mandible following repeated BTX injections into the masseter [5]. A common observation is a reduction in the width of the lower jaw as a result of muscle atrophy induced by BTX [5]. This slimming effect is most prominent in the lower third of the face. Whether this reduction in jaw width is due to muscle atrophy alone or whether it involves bone resorption is still debated [5]. Tsai et al. reported significant changes in mandibular morphology in rats following unilateral BTX injections into the masseter. Specifically, they observed a reduction in the mandibular ramus and an increase in the length of the mandible between the mandibular condyle and the incisor [5]. In humans, a clinical case report of a woman receiving repetitive BTX injections every three months for oromandibular dystonia revealed condylar bone resorption on the injected side, detected through dynamic magnetic resonance imaging [6]. These findings suggest that BTX injections may indeed contribute to changes in bone structure, particularly in the mandibular condyle. 

Bone Density Changes 

The impact of BTX on bone density remains controversial. Some studies suggest that multiple BTX injections into the masseter may lead to a reduction in bone volume, particularly in the mandibular angle area [7]. A study on human subjects who received repeated BTX injections found no change in the shape of the mandible after a single injection, but noted that repeated injections affected bone volume, consistent with findings from animal models [7]. Studies on rats and mice have demonstrated that BTX injection into the hind limb muscles resulted in decreased bone mineral content and reduced bone volume, further supporting the hypothesis that BTX can influence bone density in a dose-dependent manner [8]. However, fewer bone changes were observed in human subjects compared to animal models, suggesting that the effect of BTX on bone density may be more pronounced in animals or may depend on factors such as the frequency of injections [7]. 

Cosmetic Effects on Facial Structure 

BTX is widely used for its cosmetic effects, particularly in facial slimming through the reduction of masseter muscle size [1]. While the aesthetic results are well-documented, the long-term impact of BTX on facial structure, particularly the underlying bone, remains less understood. Some researchers have raised concerns that prolonged use of BTX may lead to changes in bone contour, potentially altering the shape of the jaw over time [5]. The long-term effects of BTX on bone, especially in patients seeking cosmetic jaw slimming, worth further investigation to assess whether these changes are reversible or if they may lead to permanent alterations in bone morphology [2]. 

Synthesis of the Literature 

The literature presents a mixed picture regarding the bone effects of BTX injections into the masseter muscle. While animal studies consistently show significant bone changes, including bone loss and altered bone density, the results in human studies are more variable [4]. The primary concern in the literature is the potential reduction in mechanical loading due to muscle paralysis, which could affect bone remodeling and lead to changes in bone turnover [4]. Despite the growing body of evidence, more longitudinal and well-controlled studies are needed to draw definitive conclusions regarding the long-term bone effects of BTX injections [4]. 

Conclusion 

While the use of botulinum toxin in the masseter muscle is well-established for therapeutic and aesthetic purposes, its potential impact on bone remains an area of active research. Current evidence suggests that BTX-induced muscle atrophy may lead to slight changes in bone density and mandibular morphology, particularly with repeated injections [5-7]. However, the long-term consequences of BTX on bone health, including the risk of bone loss or fractures, are not yet fully understood [4]. Further studies, particularly longitudinal trials, are required to assess the cumulative effects of BTX injections on the jawbone and to establish clearer guidelines for its safe use in patients with ongoing or frequent treatments.  

References 

1. Melo JB, Buvinic S. Mandibular bone loss: a hidden side effect of botulinum toxin type A injection in masticatory muscles. Journal of Oral Research. 2018;7(2):44-6. 

2. Balanta-Melo J, Toro-Ibacache V, Kupczik K, Buvinic S. Mandibular bone loss after masticatory muscles intervention with botulinum toxin: an approach from basic research to clinical findings. Toxins. 2019 Feb 1;11(2):84. 

3. Hong SW, Kang JH. Decreased mandibular cortical bone quality after botulinum toxin injections in masticatory muscles in female adults. Sci Rep. 2020; 10 (1): 3623 [Internet]. 

4. Kahn A, Kün-Darbois JD, Bertin H, Corre P, Chappard D. Mandibular bone effects of botulinum toxin injections in masticatory muscles in adult. Oral surgery, oral medicine, oral pathology and oral radiology. 2020 Feb 1;129(2):100-8. 

5. Tsai CY, Huang RY, Lee CM, Hsiao WT, Yang LY. Morphologic and bony structural changes in the mandible after a unilateral injection of botulinum neurotoxin in adult rats. Journal of oral and maxillofacial surgery. 2010 May 1;68(5):1081-7. 

6. Aziz J, Awal D, Ayliffe P. Resorption of the mandibular condyle after injections of botulinum toxin A. The British journal of oral & maxillofacial surgery. 2017 Nov;55(9):987-8. 

7. Lee HJ, Kim SJ, Lee KJ, Yu HS, Baik HS. Repeated injections of botulinum toxin into the masseter muscle induce bony changes in human adults: A longitudinal study. The Korean Journal of Orthodontics. 2017 Jul 1;47(4):222-8. 

8. Warner SE, Sanford DA, Becker BA, Bain SD, Srinivasan S, Gross TS. Botox induced muscle paralysis rapidly degrades bone. Bone. 2006 Feb 1;38(2):257-64.