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Treatments for TMD Clicking with Symptoms: An Evidence-Based Study of the Literature Tarun Bablani BSc, Jeanie Luong HBSc, Christine Magalhaes HBSc, Indervir Mann HBSc, Audrey McNamara BSc, and Victoria Ngo BSc

Department of Community Dentistry Faculty of Dentistry University of Toronto 124 Edward Street Toronto, ON M5G 1G6 Correspondence to: Audrey McNamara 124 Edward Street, Toronto, ON M5G 1G6 [email protected], 416.979.4750 ext. 3534 Word Count: 2,112

2 Abstract This evidence-based study of the literature investigated the most efficacious treatment options for TMJ clicking presenting with at least one other TMD symptom in adult populations over 21 years of age. The review was based on evidence from randomizedcontrolled trials found through 1) a search of several electronic bibliographic databases, a review of the reference lists from relevant articles, and hand-searches of relevant periodicals. A total of 20 unique articles were reviewed, and of these, 6 were critically appraised and scored according to the “checklist to assess evidence of efficacy of therapy” comprising 18 items. Four categories for TMD therapies were identified: occlusal splints, surgery, pharmacotherapy, and physical therapy/acupuncture. None of the studies achieved a score below 12 out of 18; however, the strength of the conclusions drawn from these reports was limited due to minor methodological flaws, small sample sizes and short-term results of less than 1 year. Therefore, long-term results and larger sample sizes are needed to demonstrate whether clicking is completely eliminated and if the findings can be generalized to the general adult population. Overall, the evidence suggests a fair recommendation for the use of intraarticular sodium hyaluronate injections for the treatment of anterior disc-displacement as well as use of therapeutic exercises of the jaw may be successful at reducing TMJ clicking in TMD patients.

MeSH key words: temporomandibular joint, clicking, temporomandibular joint disorder therapy/treatment

3 Introduction: Temporomandibular joint (TMJ) disorder is a broad term that encompasses several distinct pathological states of the TMJ. The origin of the TMJ disorder may be 1) extracapsular, involving primarily the muscles of mastication around the TMJ1, 2) intracapsular, as a result of abnormalities of the articular surfaces or the mechanical relationship of the joint2, or 3) a combination of extra- and intra-articular elements. Currently, our understanding of TMJ disorder etiology is limited3, and diagnostic classification is based on less objective signs and symptoms4. The most common symptoms are pain, dysfunction and joint sounds. In Canada, TMJ sounds are prevalent in 25.4% of the population5 and specifically TMJ clicking, which is the most common joint sound, is present in 21-40% of Swedish, American and Turkish TMD patient population and 4-28% of the general population6,7,8. It is also predominant in females6 and older individuals9. Clicking most commonly results from displacement of the articular disc and irregularities in the articular surface10,11. It is not known whether TMJ clicking alone represents a harmless condition or an indication of a joint that is predisposed to progressive pathology. The notion that untreated clicking in adolescence may lead to painful locked jaw in adulthood was investigated in a longidutinal study by Könönen12, and their findings did not substantiate this concern. Patients diagnosed with the condition disc-displacement with reduction that present with clicking have a better quality of life compared to patients with more severe forms of TMD (e.g. myofascial pain). However, despite having a better quality of life, some patients still find the clicking bothersome and may seek treatment to correct it13. In rare

4 cases, TMJ clicking is loud enough to be socially disturbing14,15. Most patients with TMJ clicking do not seek treatment until other TMJ symptoms, most commonly pain, develop16. Treatment modalities are generally classified into conservative measures, such as occlusal splints and masticatory exercise, non-conservative surgical interventions, such as condylectomy. Whether or not to exhaust all conservative treatments before proceeding to non-conservative even irreversible options at the risk of allowing the condition to worsen by not providing the most appropriate therapy in a timely manner, is fiercely debated in the literature17,18. The aim of this study was to evaluate the literature, and present the strongest evidence currently available to address the question: what are the most efficacious treatment options for TMJ clicking presenting with at least one other TMD symptom in adult populations over 21 years of age? Based on our findings, we offer our evidencebased recommendations for the management of patients seeking treatment for TMJ clicking and our suggestions for further research.

Methods A systematic method was used to identify, select and critically appraise relevant studies. Search Strategy Three types of searches were conducted to locate potentially relevant published articles. First, electronic bibliographic databases were searched: PubMed (1996-present), MEDLINE (1966- present), Cochrane reviews, IADR Abstracts, Scopus, and Embase.

5 The following key words were used in the preliminary search: TMJ clicking, TMJ sounds, TMD, TMJ treatment, and TMJ therapy. The categories for TMD therapies were identified as 1) Occlusal splints, 2) Surgery, 3) Pharmacotherapy, and 4) Physical Therapy/Acupuncture. Using these treatment categories, the electronic databases were searched again using “TMD clicking” plus the following key words: splint, occlusal splint, splint therapy, oral appliance, surgery, arthroscopy, arthrocentesis, condylectomy, discectomy, anesthetic, botulinum toxin, hyaluronic acid, dental acupuncture, physical therapy, manual therapy and therapeutic exercise. Second, the reference lists from articles deemed relevant to the review (see explanation below) were examined. Thirdly, relevant periodicals (Evidence-Based Dentistry and Journal of Oral Maxillofacial Surgery) were hand-searched. These searches were limited to studies of human subjects published in peer-reviewed journals in English. Determination of Relevance All articles of interest to this study were available in the Dental Library at the University of Toronto, and no articles were excluded because of unavailability from the University library holdings. Articles were rejected systematically at the title, abstract, full-length article, and lastly, the critical appraisal stage. An article was considered relevant if it met the following criteria. 1) The study evaluated TMJ clicking, not crepitation, at baseline and after treatment intervention. 2) The article reported original research. Review articles, systematic reviews, meta-analyses, commentaries and expert opinion reports were excluded. 3) The study was a randomized controlled clinical trial

6 or randomized clinical outcome study. Prospective and retrospective studies as well as case series and case reports were excluded. A list of the excluded articles and the reasons for exclusion appears in Appendix 1. 4) The population studied was adults, defined as 21 years or older. This process yielded 22 potentially relevant articles to be evaluated at the critical appraisal stage. Validity Instrument After elimination of 2 duplicate articles, resulting from overlap between surgical and drug therapies, A total of 20 unique articles were retrieved and scored by two evaluators, independently, according to a “checklist to assess evidence of efficacy of therapy or prevention” developed by Leake19 (Table 1). The highest possible score was 18. Results The literature search produced six relevant articles20,21,22,23,24,25 addressing three treatment options for TMD clicking and symptoms which satisfied our search criteria, including surgical injections with sodium hyaluronate, occlusal splints and alternative therapies of acupuncture and therapeutic exercise (Table 2). Other possible treatments that were discovered in the initial search such as arthroscopic surgery, muscle relaxants (e.g. botox), or anti-inflammatory agents (e.g. corticosteroids) did not meet our search criteria in terms of study design and were excluded from this evidence-based report. As seen in the evidence table (Table 2), each treatment category has two articles: surgical injections (Bertolami et al. & Hepguler et al.), occlusal splints (Conti et al. &

7 Truelove et al.) and alternative treatments of acupuncture and therapeutic exercise (Smith et al. & Yoda et al. respectively). The studies originated from the United States, Turkey, Brazil, the UK and Japan. All studies were small in sample size and short in duration. Each paper presented more females than males in the sample size, however this was expected according to data on TMD prevalence, and both genders were evenly distributed amongst the groups. No study scored less than 12/18, which therefore met our checklist criteria. For surgical injections, the papers both focused on injecting sodium hyaluronate in the treatment group, and saline as a placebo in the control. Data from Bertolami et al. was only included from the DDR (displaced disc with reduction) group, because these subjects presented with joint clicking upon diagnosis. TMD clicking as an outcome was measured by visual analog scale (VAS) and electronic devices (e.g. accelerometer), and was noticeably reduced in the treatment group compared to the placebo in both studies during the 6 month follow-up. Bertolami et al. reports these findings first, and Hepguler et al. confirms the outcome nearly 10 years later in a similarly designed study. Occlusal splint therapy examined by Conti et al. compared bilaterally balanced splints and canine guided splints in the treatment group to non-occluding splints in the control. Joint clicking measured by VAS and palpation was significantly reduced in all groups during the 6 month duration; however, the results were not significant between the groups. Truelove et al. compared treatment groups using hard and soft splints with a control group that used the usual treatment (i.e. dentist-prescribed, reversible self-care

8 strategies such as NSAIDs and thermal packs). For all three groups, joint clicking did not change from baseline during the 12 month follow-up. Acupuncture therapy assessed by Smith et al. compared real acupuncture with a placebo group using a park sham device (a blunt needle that looks like a real needle), however, the study presented no improvements in joint clicking for either group measured by VAS. Physical therapy exercises by Yoda et al. compared the therapeutic exercises with a no treatment group. It was observed that there was a 61.9% success rate in decreased clicking in the treatment compared to the control group.

Discussion There are few studies that report on the therapeutic outcome for TMJ clicking alone, but rather, studies tend to look at all TMD symptom outcomes, which may or may not include joint clicking16. Some individuals postulate that clicking may not even be pathologic26, and consequently, treatments target TMD symptoms as a whole or its more pathological symptoms (e.g. pain or minimal jaw opening). Because of the lack of studies that focused solely on TMJ clicking as an outcome, papers were selected that evaluated TMD patients with clicking at baseline, and following treatment. Sodium hyaluronate is a high-molecular-weight polysaccharide that is a natural component of synovial fluid, playing an important role in lubricating and maintaining the joint environment27. TMD clicking is reduced in subjects injected with short-term therapy of sodium hyaluronate compared to the saline placebo, however, long-term effects are not known. It also is not known whether there is a dose-dependent

9 relationship between sodium hyaluronate and the reduction of clicking and symptoms since neither investigator measured this. Nevertheless, the results are reliable since Hepguler et al. was able to reproduce the results by Bertolami et al. nearly a decade later. Sodium hyaluronate is reported as safe20, and treatment subjects presented with mild adverse symptoms that were short in duration which were no different from the placebo’s adverse effects. Occlusal splint therapy is the most common form of TMD treatment used22. The mechanism of action is unclear, however, some suggest that splints may increase the vertical dimension of occlusion, achieve the “ideal” occlusion, relax the muscles or have a cognitive effect23. The use of occlusal splints as a major treatment option for TMD pain has been shown to be effective; however, the same cannot be said for TMD clicking. In the study by Conti et al., the control groups (non-occluding splints) were just as effective as the intervention groups (occluding splints) in mildly decreasing clicking prevalence. The findings by Truelove et al., were similar suggesting that the treatment intervention was not effective. The mild decrease in clicking in these groups could be explained in part by the ‘placebo effect’. Also, the positive relationship between the dental practitioner and the patient’s feeling of being treated may also influence the final results23. Acupuncture involves the insertion of fine needles at specific “acupuncture points” on the body surface, which are thought to be near the area where pain is experienced28, however it is not known how acupuncture may influence TMJ clicking. In the study by Smith et al., acupuncture did not significantly reduce joint clicking in the

10 treatment group. However, the results may not be validly measured, as all subjects were reassessed for outcome measurements only one week after treatment, therefore, later effects are not known. The authors note that the park sham credibility is high because none of the patients believed that they were treated with the sham needle. Therapeutic exercises performed by subjects in the study by Yoda et al., involves the movement of the jaw in protrusive, opening and closing positions. Movement of the jaw is thought to decrease joint noises because the exercises increase the joint space, which allows for smoother condylar translation without clicking24. Yoda et al. reports a moderate success rate in reducing clicking in the therapeutic exercise group in the short-term. In addition to the positive results, therapeutic exercises may be considered the most cost-effective treatment option for TMD clicking.

Conclusion The evidence from the literature is weak to suggest the most effective treatment for TMJ clicking. All six papers in this literature review had small sample sizes, thus, it is difficult to apply these results to the general population because of the weak external validity. Another major weakness of all the papers was the short-term duration of the studies, hence, the long-term effects of the therapeutic interventions examined on TMD clicking are not known. Nevertheless, the promising short-term results from sodium hyaluronate injections suggests that the therapy may have long-term value if the injections are given serially, every 3 to 6 months as required. Therefore, to further determine which therapy is most effective at reducing TMD clicking, studies of larger

11 sample size and longer in duration (>2 years) are recommended. As well, future studies should also strive to compare different treatment options in the same population by utilizing strongly designed RCTs in order to accurately propose the best therapy to reduce TMD clicking. The evidence suggests that therapeutic exercises of the jaw would be successful at reducing clicking in TMD symptom patients, and that intraarticular sodium hyaluronate injections may be successful for treatment of TMJ clicking in anterior disc-displacement. Sodium hyaluronate and therapeutic exercises are also considered safe therapies, and the therapeutic exercises are presumably the most costeffective therapy for TMD clicking. Therefore, we recommend sodium hyaluronate injections and therapeutic exercises for short-term use in reducing clicking in patients that are considered problematic or bothersome.

12 Acknowledgment The authors wish to thank Dr. D. Ito for his guidance and feedback throughout the course of this study and preparation of this manuscript. Conflict of Interest The authors declare no financial interests.

13 References 1. Clark GT, Merrill RT. Diagnosis and non-surgical treatment of masticatory muscle pain and dysfunction. In: The Temporomandibular joint: a biological basis for clinical practice 1996 (eds BG Sarnat and DM Laskin)pp. 346-356. PA saunders, Philedelphia. 2. Guralnick W, Kaban LB, Merrill RG. Temporomandibular-joint afflictions. New Eng J Med 1978; 299(3):123-9. 3. Greene CS. The etiology of temporomandibular disorders: Implications for Treatment. J Orofacial Pain 2001; 15(2):93-105. 4. Reston JT, Turkleson CM. Meta-analysis of surgical treatments for temporomandibular articular disorders. J Oral Maxillo Surg 2003; 61:3-10. 5. Locker D, Slade G. Association of symptoms and signs of TM disorders in an adult population. Comm Dent Oral Epidemiol 1989;17(3):150-3. 6. Elfving L, Helkimo M, Magnusson T. Prevalence of different temporomandibular joint sounds, with emphasis on disc-displacement, in patients with temporomandibular disorders and controls. Swed Dent 2002; 26(1):9-19. 7. LeResche L. Epidemiology of temporomandibular disorders: Implications for the investigation of etiologic factors. Crit Rev Oral Biol Med 1997; 8(3): 291-305. 8. Nekora-Azak A, Evlioglu G, Ordulu M, Işsever H. Prevalence of symptoms associated with temporomandibular disorders in a Turkish population. J Oral Rehab 2006;33(2):81-4. 9. Schmitter M, Rammelsberg P, Hassel A.The prevalence of signs and symptoms of TMD in very old subjects. J Rehab 2005; 32(7): 46-73. 10. Miller TL, Katzberg RW, Tallents RH, Bessette RW, Hayakawa K. Temporomandibular joint clicking with nonreducing anterior displacement of the meniscus. Radiology 1985; 154(1):121-4. 11. Widmalm SE, Westesson PL, Brooks SL, Hatala MP, Paesani D. Temporomandibular joint sounds: correlation to joint structure in fresh autopsy specimens. Am J Orthod Dentofacial Orthop 1992;101(1):60-9. 12. Könönen M, Waltimo A, Nyström M. Does clicking in adolescence lead to painful temporomandibular joint locking? Lancet 1996; 347:1080-1081.

14 13. Reissmann DR, John MT, Schierz O, Wassell RW. Functional and psychosocial impact related to specific temporomandibular diagnoses. J Dent 2007; 35: 643-50. 14. Homlund A. Disc derangements of the temporomandibular joint: A tissue-based characterization and implications for surgical treatment. Int J Oral Maxillofac Surg 2007; 36:571-576. 15. Yoda T, Imai H, Shinjyo Y, Sakamoto I, Abe M, Enomoto S. Effect of arthrocentesis on TMJ disturbance of mouth closure with loud clicking: A preliminary study. Cranio 2002; 20(1):18-22. 16. Spruijt RJ, Wabeke KB. Psychological factors related to the prevalence of temporomandibular joint sounds. J Oral Rehab 1995; 22:803-808. 17. Dimitroulis G. The role of surgery in the management of disorders of the Temporomandibular Joint: a critical review of the literature. Part 1. Int J Oral Maxillofac Surg 2005; 34(2):107-13. 18. Dimitroulis G. The role of surgery in the management of disorders of the temporomandibular joint: a critical review of the literature. Part 2. Int J Oral Maxillofac Surg 2005; 34(3):231-7. 19. Leake JL, Department of Biological and Diagnostic Sciences, Faculty of Dentistry, University of Toronto. Unpublished document. Course notes DENT 300Y 2007. The checklist was adapted from Fletcher RH, Fletcher SW, Wagner EH. Clinical epidemiology. The essentials. 3rd ed. Baltimore: Williams and Wilkins, 1996; and Sackett DL, Richardson WS, Rosenberg W, Haynes RB. Evidence-based medicine: how to practice and teach. EBM. 2nd ed. New York: Churchill Livingstone, 1997. 20. Bertolami CN, Gay T, Clark GT, Rendell J, Shetty V, Liu C, Swann DA. Use of sodium hyaluronate in treating temporomandibular joint disorders. J Oral Maxillofac Surg 1993; 51: 232-242. 21. Hepguler S, Akkoc YS, Pehlivan M, Ozturk C, Celebi G, Saracoglu A, Ozpinar B. The efficacy of intra-articular sodium hyaluronate in patients with reducing displaced disc of the temporomandibular joint. J Oral Rehab 2002;29: 80-86. 22. Truelove E, Huggins KH, Mancl L, Dworkin SF. The efficacy of traditional, low-cost nonsplint therapies for temporomandibular disorder. J Amer Dent Assoc 2006; 137: 10991107.

15 23. Conti PC, dos Santos CN, Kogawa EM, de Castro Ferreira Conti AC, de Araujo Cdos R. Treatment of painful temporomandibular joint clicking with oral splints. J Amer Dent Assoc 2006; 137: 1108-1114. 24. Yoda T, Sakamoto I, Imai H, Honma Y, Shinjo Y, Takano A, Tsukahara H, Morita S, Miyamura J, Yoda Y, Sasaki Y, Tomizuka K, Takato T. A randomized controlled trial of therapeutic exercise for clicking due to anterior disk displacement with reduction in the temporomandibular joint. Cranio 2003; 21(1): 10-16. 25. Smith P, Mosscrop D, Davies S, Sloan P, Al-Ani Z. The efficacy of acupuncture in the treatment of temporomandibular joint myofascial pain: a randomized control trial. J Dent 2007; 35(3): 259-267. 26. Kurita H, Kurashina K, Kotani A. Clinical effect of full coverage occlusal splint therapy for specific temporomandibular disorder conditions and symptoms. J Prosth Dent 1997;78(5):506-10. 27. Shi Z, Guo C, Awad M. Hyaluronate for temperomandibular joint disorders (review). The Cochrane Library. 2007, Issue 4. 28. Wong J. A manual of neuro-anatomical acupuncture. 1st ed. Toronto, Ontario: The Toronto Pain and Stress Clinic Inc.; 1999.

16 Table 1

Checklist for assessing evidence of efficacy of therapy or prevention19.

General questions 1. Was the study ethical? 2. Was a strong design used to assess efficacy? 3. Were outcomes (benefits and harms) validly and reliably measured? 4. Were the interventions validly and reliably measured? Questions about the results of the study 5. Was the treatment effect large enough to be clinically important? 6. Was the estimate for the treatment effect beyond chance and relatively precise? 7. If the findings were ‘no difference’, was the power of the study 80% or better? Questions about the validity of the results 8. Was the assignment o patients to treatments randomized? 9. Were all patients who entered the trial properly accounted for and attributed at its conclusion? 10. Was loss to follow-up less than 20% and balanced between test and controls? 11. Were patients analyzed in the groups to which they were randomized? 12. Was the study of sufficient duration? 13. Were patients, health care workers and study personnel “blind” to treatment? 14. Were the groups similar at the start of the trial? 15. Aside from the experimental intervention, were the groups treated equally? 16. Was care received outside the study identifies and controlled for? Clinical relevance of the results 17. Were all clinically important outcomes considered? 18. Are the likely benefits of treatment worth the potential harms and costs?

17

18

19

20 Appendix 1 List of articles excluded and reasons for exclusion Articles Homlund and others 2001; Politi and others 2007; Alpaslan and Alpaslan 2001

Yoda and others 2002 Fridrich and others 1996

Wassell and others 2004; Wassell and others 2006 Alvarez-Arenal and others 2002; Jagger 1991 Bjornland and others 2007; Schiffman and others 2007; Alpaslan and others 2000 Raustia and others 1985; Johansson and others 1991

Reason for exclusion Patients did not have TMJ click at baseline Major flaws in methodology. Joints assessed not always in different patients (i.e. some patients had bilaterally affected TMJ). Accuracy of the diagnosis at baseline is questionable as closed lock should not present with clicking. Lack of detailed description of how outcome measurements were made. Non-randomized controlled trial Major flaws in methodology. Study personnel conducting follow-up evaluation were not blinded, joints assessed were not all in different patients (i.e. some patients had bilaterally affected TMJs) and objective data regarding joint noises pre- and post-operatively was collected from patients but not reported in the study. Loss to follow-up greater than 20%, and the study was a unilateral rather than bilateral cross-over design. No control group Did not examine TMJ clicking no placebo for acupuncture; drop-out rate not specified.

Alpaslan GH, Alpaslan C. Efficacy of temporomandibular joint arthrocentesis with and without injection of sodium hyaluronate in treatment of internal derangements. J Oral Maxillofac Surg 2001;59(6):613-8. Alvarez-Arenal A, Junquera LM, Fernandez JP, Gonzalez I, Olay S. Effect of occlusal splint and transcutaneous electric nerve stimulation on the signs and symptoms of temporomandibular disorders in patients with bruxism. J Oral Rehab 2002; 29(9):858863.

21 Bjornland T, Gjaerum AA, Moysta A. Osteoarthritis of the temporomandibular joint: an evaluation of the effects and complications of corticosteroid injection compared with injection with sodium hyaluronate. J Oral Rehab 2007;34:583-589. Fridrich KL, Wise JM, Zeitler DL. Prospective comparison of arthroscopy and arthrocentesis for temporomandibular joint disorders. J Oral Maxillofac Surg 1996; 54(7):816-820 Holmlund A, Axelsson S, Gynther GW. A comparison of discectomy and arthroscopic lysis and lavage for the treatment of chronic closed lock of the temporomandibular joint: A randomized outcome study. J Oral Maxillofac Surg 2001;59(9):972-977. Jagger RG. Mandibular manipulation of anterior disc displacement without reduction. J Oral Rehab 1991; 18:373-382. Johnasson A, Wenneberg B, Wagerstern C, Haraldson T. Acupuncture in treatment of facial muscular pain. Acta Odontol Scand 1991; 49:153-158. Politi M, Sembronio S, Robiony M, Costa F, Toro C, Undt G. High condylectomy and disc repositioning compared to arthroscopic lysis, lavage, and capsular stretch for the treatment of chronic closed lock of the temporomandibular joint. OOOOE 2007;103(1): 27-33. Raustia AM, Pohjola RT, Virtanen KK. Acupuncture compared with stomatognathic Treatment for TMJ dysfunction. Part I: A randomized study. J Prosthet Dent 1985; 54:581-585. Schiffman EL, Look JO, Hodges JS, Swift JQ, Decker KL, Hathaway KM, Templeton RB, Fricton JR. Randomized Effectiveness Study of Four Therapeutic Strategies for TMJ Closed Lock. J Dent Res 2007; 86(1):58-63. Wassell RW, Adams N, Kelly PJ. Treatment of temporomandibular disorders by stabilising splints in general dental practice: results after initial treatment. Brit Dent Jour 2004; 197:35–41. Wassell RW, Adams N, Kelly PJ. The treatment of temporomandibular disorders with stabilizing splints in general dental practice: One-year follow-up. J Am Dent Assoc 2006; 137(8): 1089-1098. Yoda T, Imai H, Shinjyo Y, Sakamoto I, Abe M, Enomoto S. Effect of arthrocentesis on TMJ disturbance of mouth closure with loud clicking: a preliminary study. Cranio 2002; 20(1):18-22.