Bone and cartilage changes after injection of botulinum toxin.

Abstract

I hope that readers opening the December 2015 issue were not surprised to find that unilateral paralysis of masseter muscles in growing rabbits should have an effect on hard tissue structures (Matthys T, Dang HA, Rafferty KL, Herring SW. Bone and cartilage changes in rabbit mandibular condyles after 1 injection of botulinum toxin. Am J Orthod Dentofacial Orthop 2015;148:999-1009). However, the 60% to 98% reduction in masseter muscle activity that was prescribed by the authors1Matthys T. Dang H.A. Rafferty K.L. Herring S.W. Bone and cartilage changes in rabbit mandibular condyles after 1 injection of botulinum toxin.Am J Orthod Dentofacial Orthop. 2015; 148: 999-1009Abstract Full Text Full Text PDF Scopus (23) Google Scholar, 2Rafferty K.L. Liu Z.J. Ye W. Navarrete A.L. Nguyen T.T. Salamati A. et al.Botulinum toxin in masticatory muscles: short- and long-term effects on muscle, bone, and craniofacial function in adult rabbits.Bone. 2012; 50: 651-662Abstract Full Text Full Text PDF PubMed Scopus (68) Google Scholar is vastly different from what would be considered appropriate therapeutic treatment with botulinum neurotoxin type A (BoNtT/A). Botulinum toxin injections are performed for clinical conditions when muscular function is aberrant, such as masseter hyperplasias, muscular dystonias, and dyskinesias. Dose selection is designed to provide precise control over the pathologically functioning muscles and return them to a healthy state, but not beyond. This is not what was evaluated in the study, and the authors' conclusions must be approached with significant reservations. The authors' calculations using muscle mass to correlate their selected doses for rabbits with those commonly prescribed for human subjects has no scientific basis. In fact, marked species differences exist in the relative potencies of various botulinum toxin serotypes and in their latency of action.3Schwartz J. Focus on biodiversity research. Nova Science Publishers, Hauppauge, NY2007Google Scholar, 4Agoston S. The origin and functions of biodiversity in infectious and non-infectious diseases.in: Kharkevich D.A. New neuromuscular blocking agents: basic and applied aspects. Springer Science & Business Media, New York2012Google Scholar Thus, attempting to correlate doses across species on the basis of muscular mass is simply improper. Herbivores, such as rabbits, “are highly sensitive to botulinum toxins of all types for which tests have been performed.”3Schwartz J. Focus on biodiversity research. Nova Science Publishers, Hauppauge, NY2007Google Scholar Their response would be disproportionate compared with that of humans. Such considerations are extremely important if we are to apply any findings to human subjects. The authors did not acknowledge or discuss any circumstances in which it would be appropriate to reduce the functional loading of the temporomandibular joint. Tissue degradation and joint effusion resulting from excessive loading conditions are as important to discussions of condylar health and joint disease as deliberate underloading. Additionally, many well-established orthodontic treatment modalities—eg, bite plates and functional appliances—operate by unloading the joint in the same fashion and without long-term negative effects. The authors' suggestion that these treatments produce lasting joint changes is extremely premature based on the length of their study. The recoveries of both bony changes and masseter volumes lag behind the reestablishment of full neuromuscular function; at 12 weeks, this had admittedly not yet occurred in their subjects. I am also puzzled by their claim regarding the possibility of BoNT/A's “direct toxicity for skeletal cells.” No such effects have been identified in the literature, and BoNT/A is currently used as a treatment for osteoarthritic conditions via intra-articular injections.5Chou C.L. Lee S.H. Lu S.Y. Tsai K.L. Ho C.Y. Lai H.C. Therapeutic effects of intra-articular botulinum neurotoxin in advanced knee osteoarthritis.J Chin Med Assoc. 2010; 73: 573-580Abstract Full Text PDF PubMed Scopus (21) Google Scholar Unfortunately, I feel that this study adds more to the myths and misunderstandings surrounding BoNT/A treatments than it does to draw attention to why proper training, case selection, and dosing are important. Bone and cartilage changes in rabbit mandibular condyles after 1 injection of botulinum toxinAmerican Journal of Orthodontics and Dentofacial OrthopedicsVol. 148Issue 6PreviewTemporary paralysis of the masseter muscle caused by botulinum toxin is a common treatment for temporomandibular disorders, bruxism, and muscle hypertrophy. Loss of masseter force is associated with decreased mandibular mineral density. Our objectives were (1) to establish whether bone loss at the mandibular condyle is regionally specific and (2) to ascertain whether the treatment affects the condylar cartilage. Full-Text PDF Authors' responseAmerican Journal of Orthodontics and Dentofacial OrthopedicsVol. 149Issue 4PreviewThe letter from Dr Frey raised several points worthy of discussion. First was the question of differential species sensitivity to botulinum toxins and whether rabbits are an appropriate model for humans, and specifically whether our rabbits were overdosed relative to typical human usage. Second, the letter noted that we failed to mention the advantages of unloading the temporomandibular joint. Third, it pointed out that our study period of 3 months was not long enough to justify our claim of lasting joint changes. Full-Text PDF