Effect of multiple injections of botulinum toxin into painful masticatory muscles on bone density in the temporomandibular complex

Abstract

Background Adverse effects of masticatory muscle injections of Botulinum Toxin (Btx) have been noted in animal and, less dramatically, human studies. Objective Among women treated in multiple community‐based private practices, to compare TMJ bone density and mandibular condylar volume between patients with myofascial TMJD receiving multiple masticatory muscle Btx treatments and similarly diagnosed women not receiving such treatment. Methods Cohorts consisted of women whose treatment charts indicated a diagnosis of myofascial TMJD: 35 received at least 2 Btx treatment cycles; 44 received none. Bone density at pre‐specified regions of interest (ROI) was defined by grey scale values from Cone Beam CT, adjusting for a fixed density phantom included in each scan. Mean bone density and mandibular condyle volume were compared between groups. Dose‐response effects were tested within the Btx‐exposed group. Results The mean density of primary and secondary ROIs was similar between exposure groups, as was condylar volume. Among Btx‐exposed women, increasing dose of Btx to the temporalis muscle was inversely proportional to the density of the trabecular area of the mandible body. Many Btx‐exposed women received smaller doses of Btx to the masseter muscles than in most TMJD Btx clinical trials. Conclusion Masticatory muscle injections of Btx failed to produce clinically significant TMJ bone‐related changes. Should Btx receive regulatory approval for treatment of myofascial TMJD, a phase IV study is recommended to evaluate potential adverse effects of Btx on bone and muscle when administered at higher doses and/or for more treatment cycles.

Muscle-Bone Crosstalk in the Masticatory System: From Biomechanical to Molecular Interactions

“…In adult women with myofascial pain, a randomized clinical trial demonstrated a significant reduction of the volume of the mandibular condylar process at 3 months, after a high BoNTA dose injection in both the temporalis (25 U) and the masseter (75 U) muscles but not at lower doses (20 U and 50 U, respectively) ( 193 ). These results are consistent with a cohort study, which showed no bone loss at the mandibular condylar process in adult women with myofascial pain that underwent BoNTA interventions under 40 U in the masseter muscles when compared to match control population ( 194 ). These results support the hypothesis that masticatory muscle hypofunction negatively impacts mandibular bone homeostasis in humans, especially at the condylar process, when high doses of BoNTA are used.…”

Impact of botulinum toxin injection into the masticatory muscles on mandibular bone: A systematic review

“…Raphael et al 31 was a cohort study assessing bony change following at least two series of BoNTA injection into the masticatory muscles within the past year for ‘myofascial TMJD’. Of note, a portion of this group also received concurrent BoNTA injections for frequent migraine therapy into various muscles of the head, face and neck, as is standard protocol for chronic migraine 32 .…”

“…This effect is arguably to be expected, as menopause is concurrent with a decrease in oestrogen production, and oestrogen inhibits osteoclastic activity 42 . BoNTA dose appears to influence bony change, with higher doses leading to greater bone loss or decreased trabecular density 26,31 . Dose frequency also appears to influence bony change, as Lee et al showed that a second BoNTA injection series 4 months after the initial series led to greater bone loss than a single series 29 .…”

“…While the results were not unanimous, 25,31 the majority of articles reviewed did report that the injection of botulinum toxin into the muscles of mastication resulted in significant bony changes to one or more areas of the mandible 26–30 . Of the measured effects, the most frequent were a decrease in bony volume, 26,29 decrease in cortical thickness 27 and a decrease in cortical or trabecular density 27,28,30,31 . The most frequently reported areas of mandibular bony change were the condylar head, the coronoid process and the mandibular ramus 26–30 .…”

Intramuscular Injections and Dry Needling within Masticatory Muscles in Management of Myofascial Pain. Systematic Review of Clinical Trials

“…However, it is worth highlighting that application of low doses of BTX did not cause any bone-related damage and is a treatment recommended by the authors [ 52 ]. On the contrary, in 2020, Raphael et al, based on a cohort consisting of 35 patients, stated that multiple Botox injections failed to produce clinically significant bone changes [ 53 ]. Nevertheless, those studies indicate that multiple BTX treatments might be a cause of some significant adverse effects, and there is a need to monitor the patients undergoing BTX therapy, especially when high doses of the toxin are applied.…”