|Year : 2020 | Volume
| Issue : 3 | Page : 216-221
Combination of trypsin, rutoside, bromelain and diclofenac sodium in the management of internal derangement of temporomandibular joint: A randomized clinical trial
Prashant Gupta1, Shantala R Naik1, L Ashok2, R Poornima2, Ranjani Shetty2
1 Department of Oral Medicine and Radiology, Dental Institute, RIMS, Ranchi, Jharkhand, India
2 Department of Oral Medicine and Radiology, Bapuji Dental College and Hospital, Davangere, Karnataka, India
|Date of Submission||19-Mar-2020|
|Date of Decision||09-Jul-2020|
|Date of Acceptance||23-Jul-2020|
|Date of Web Publication||29-Sep-2020|
Dr. Shantala R Naik
Dental Institute, RIMS, Ranchi - 834 009, Jharkhand
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Background: Internal derangement of temporomandibular joint (TMJ) is a chronic disease which causes a considerable amount of pain and reduced chewing ability and thus compromising patients eating ability and lifestyle. Aims: This study was carried out to evaluate the clinical effectiveness of enzymes like trypsin, rutoside, bromelain, and diclofenac combination against the use of diclofenac alone in the treatment of internal derangement (ID) of TMJ. Settings and Design: This study was done in the OPD of Oral Medicine and Radiology department at dental institute and is a randomized case-controlled clinical trial. Methods and Materials: 30 subjects were enrolled in the study by simple random sampling and were diagnosed clinically as ID and radiographically screened. They were divided into 2 groups of 15 each. Group I was given oral diclofenac sodium and group II was given an oral combination of trypsin, rutoside, bromelain, and diclofenac sodium for a span of 14 days. Statistical Analysis: It was done by comparing the mean, median, and standard deviation of each variable. Comparative analysis was done using the Mann–Whitney U test, Friedman's test, Chi-square test, Student's t-test, and ANOVA to find the P- value and confidence interval. Results: Both the groups had reduced pain, improved chewing ability and mouth opening, and reduction in joint noise and jerky mandibular movements. Group I, patients had better results when compared to group I and the differences were highly significant. Conclusion: We recommend the use of a combination of enzymes and diclofenac for the management of ID of TMJ.
Keywords: Diclofenac, oral enzymes, TMD
|How to cite this article:|
Gupta P, Naik SR, Ashok L, Poornima R, Shetty R. Combination of trypsin, rutoside, bromelain and diclofenac sodium in the management of internal derangement of temporomandibular joint: A randomized clinical trial. J Indian Acad Oral Med Radiol 2020;32:216-21
|How to cite this URL:|
Gupta P, Naik SR, Ashok L, Poornima R, Shetty R. Combination of trypsin, rutoside, bromelain and diclofenac sodium in the management of internal derangement of temporomandibular joint: A randomized clinical trial. J Indian Acad Oral Med Radiol [serial online] 2020 [cited 2022 Jun 30];32:216-21. Available from: https://www.jiaomr.in/text.asp?2020/32/3/216/296584
| Introduction|| |
Temporomandibular disorders (TMD) cause pain or discomfort of the temporomandibular joint (TMJ). Internal derangement (ID) is defined as a disruption within the internal aspects of TMJ in which there is a disruption of the disc from its normal functional relationship with the mandibular condyle and the articular portion of the temporal bone.
ID is the most common cause of TMD. It occurs due to a displaced disc. ID can be classified as disc displacement with reduction, disc displacement with reduction and intermittent locking, disc displacement without reduction, and disc displacement without reduction and perforation. ID with reduction has a possible minimum mouth opening. ID without reduction doesn't have any possible mouth opening. ID is the common cause for clicking and jaw locking. It manifests with chronic pain localized to the TMJ area and aggravates on jaw manipulation. It causes restricted mouth opening and deviation of the mandible.
The etiology for ID could be mechanical or psychogenic causes. Nonsurgical management is still the gold standard treatment for over 90% of the population. The clinical assessment of ID is done by detailed history, clinical examination, and investigations. There are three cardinal features of ID: orofacial pain, joint noise, and restricted jaw function. Patients also have reduced laterotrusive movements, an intermittent lock of joint, deflection, or deviation of the mandible and accompanied myalgia. The patient complains of joint noise, which is a common finding in an asymptomatic individual. Unless joint noise becomes painful, the absence of pain makes this joint noise of little clinical significance. Pain anterior to tragus, projecting to ear, temple, cheek, and along mandible are all diagnostic of ID. It may be accompanied by clicks in the preauricular area.
Proteolytic enzymes are being used since 1960 and their main mechanism of action is to facilitate tissue repair. The combination of trypsin and chymotrypsin provides quick recovery. Combination of bromelain, rutoside, and trypsin has analgesic, anti-inflammatory, anti-edematous, and antioxidant properties.,
This combination has been used in the treatment of other joints of the body. The fact that these enzymes help in tissue repair, and ID has inflammation of synovial membrane, hence combination of proteolytic enzymes with painkillers could be beneficial. This study aimed to study the efficacy of trypsin, bromelain, rutoside trihydrate, and diclofenac sodium in the ID of TMJ.
| Methodology|| |
All patients included in the study were from the OPD of the Dental Institute. Simple random sampling was done to avoid selection bias. Those cases of ID, which fulfilled the criteria for ID, as discussed above, were included.
Group I included 15 patients with ID who were given diclofenac sodium 50mg (Dilona D, Mapra) twice daily for 14 days and were advised jaw exercises and moist heat application.
Group II included 15 patients with ID who were given a combination of Trypsin 48mg, Bromelain 90mg, Rutoside trihydrate BP 100mg, and Diclofenac sodium 50mg (Zymoflam D, Aristo Pharma) twice daily for 14 days along with jaw exercises and moist heat application.
Jaw exercises like slow guided opening and closing of jaws, lateral movements of the lower jaw, open the mouth, and touch the tip of the tongue to the palate and then slowly close the mouth. This was done at least 4 times a day. Moist heat application for painful TMJ was done 4 times a day. These exercises and moist heat applications were advised for the next 14 days and could be carried on if mild symptoms persisted. Patients were also advised to support jaw while widely opening the mouth, like when yawning, avoiding to eat larger chunks of food and rather eat smaller bites, and avoiding to eat hard food and follow soft diet pattern as long as symptoms persisted.
All the patients were evaluated clinically and screened radiographically (orthopantomogram) and scores were recorded on day 1. A detailed history was the key for the diagnosis of ID, and functional classification of ID was used. OPG was done to rule out arthritic changes or degenerative joint diseases. They were recalled after day 5, day 7, and day 14. Scores were recorded on these consecutive days.
All the patients were evaluated for the following parameters:
- Pain score was assessed subjectively by a numerical rating scale from 1to 10 (0 for no pain, 10 for most intense pain imaginable)
- Mouth opening assessed by interincisal mouth opening
- Chewing ability assessed subjectively by numerical rating score from 1to 10 (0 for normal, 10 for unable to chew)
- Joint noise assessed subjectively by history taking
- Jerky mandibular movements evaluated clinically by palpating jaw movements
Scoring was tabulated for each of the above parameters.
Any patient who fulfills the criteria for ID of TMJ, were part of the study:
- Pain in the TMJ region
- The decrease in mouth opening (the normal values of maximum interincisal mouth opening are between 35 and 50 mm) and laterotrusive movements (the normal values of the ipsi and contralateral movements of the joint are between 5 and 10 mm)
- TMJ noise
- Intermittent lock of the joint
- Deflection or deviation of the mandible during mouth opening
TMJ pain which does not fulfill the above mentioned criteria was excluded from the study.
- Radiographic evidence of degenerative joint disease
- A positive history of major trauma.
Statistical analysis was done by comparing, mean, median, and standard deviation of each variable. Comparative analysis was done using the Mann–Whitney U test, Friedman's test, Chi-square test, Student's t-test, and ANOVA to find the P- value and confidence interval.
| Results|| |
[Table 1] and [Figure 1] reveals a comparative evaluation of the pain score of TMJ between groups I and II patients of ID of TMJ at different follow-up. The normalcy of data was checked by Kolmogorov and Smirnov test and it showed data distribution was skewed, so a nonparametric test was applied to find a significant difference. At baseline, there was statistically no significant difference found between groups I and II. At first and second follow-up, there was a statistically significant difference found between groups I and II. There was a statistically highly significant reduction found in mean pain score from baseline to third follow-up (P- value 0.001).
|Table 1: Comparative evaluation of pain score in TMJ between groups I and II patients of Internal derangement of TMJ|
Click here to view
|Figure 1:Comparative evaluation of pain score in TMJ between groups I and II patients of internal dearangement of TMJ at different follow-up|
Click here to view
[Table 2] and [Figure 2] reveals comparative evaluation of chewing ability score of TMJ between groups I and II patients of ID of TMJ at different follow-up. At baseline, there was statistically no significant difference found between groups I and II in the chewing score. At first and second follow-up, there was a statistically significant difference found between groups I and II. There was a statistically highly significant improvement found in mean chewing ability from baseline to third follow-up (P = 0.00).
|Table 2: Comparative evaluation of Chewing ability score between groups I and II patients of Internal derangement of TMJ|
Click here to view
|Figure 2: Comparative evaluation of chewing ability score between groups I and II patients of internal dearangement of TMJ at different follow-up|
Click here to view
[Table 3] reveals the comparative evaluation of mouth opening between groups I and II patients of ID of TMJ. There was statistically no significant difference found in mean mouth opening between groups I and II at all follow-up. But there was statistically significant improvement found in both the groups from baseline to the last follow-up.
|Table 3: Comparative evaluation of mouth opening between groups I and II patients of Internal derangement of TMJ|
Click here to view
[Table 4] reveals comparative evaluation of TMJ noise between groups I and II patients of ID of TMJ. Joint noise significantly reduced at second and third follow-up. There was statistically significant difference found in joint noise between groups I and II at second and third follow-up.
|Table 4: Comparative evaluation of TMJ joint noise between groups I and II patients of Internal derangement of TMJ|
Click here to view
[Table 5] reveals the comparative evaluation of TMJ jerky movement between groups I and II patients of ID of TMJ. Jerky movement significantly reduced at second and third follow-ups. There was a statistically significant difference found in joint noise between groups I and II at the second and third follow-up.
|Table 5: Comparative evaluation of TMJ Jerky movement between groups I and II patients of Internal derangement of TMJ|
Click here to view
| Discussion|| |
TMD is a collective term used for TMJ-related disorders. Most commonly we encounter masticatory muscle pain which could limit TMJ movement. Maxillary sinusitis could also result in TMJ pain and limit the chewing ability of patients. Odontogenic cause also exists. Maxillary and mandibular posterior tooth pain could also radiate to TMJ. Then comes the ID of TMJ. Chronic occlusal irregularities and long-term orthodontic treatment are few of the causes to be listed. These irregularities could alter the disc eminence relationship and thereby cause discal changes and hence ID.
Oral enzymes are called as unsung heroes of the body. Life would be impossible without them. There are about 50,000 different types of enzymes in the human body. They have a very important role in inflammation and other functions related to the immune system. Inflammation is the body's key mechanism for protecting the body from danger. This is how our body tries to defend the long-term health of our body.,
Proteolytic enzymes like bromelain, papain, pancreatin, trypsin, chymotrypsin, and rutin are essential regulators and modulators of inflammatory response. It increases the activity of macrophages and potentiality of natural killer cells by several folds. Enzymes also disintegrate pathogenic complexes that could inhibit normal immune function. These immune complexes are part of the regular immune response. Also, when these immune complexes occur in excess, they become the principal cause for several diseases like kidney disease, nerve inflammation, and rheumatologic disease. The proteolytic enzymes help to break up existing pathogenic immune complexes and it also prevents their formation, enhancing lymphatic drainage. This provides a regulatory or stimulatory effect on the immune system.
Proteolytic enzymes regulate the inflammatory process in many ways, which include a reduction in swelling of the mucous membrane, decrease the capillary permeability, and dissolve the blood clot, fibrin deposits, and microthrombi. It also reduces the viscosity of blood, thereby improves circulation. This increases the supply of oxygen and nutrients to the traumatized tissues and also the transport of harmful waste products away from traumatized tissue. It also helps to break down plasma proteins and cellular debris at the site of injury into small fragments that could be drained into the lymphatic system, thereby reducing swelling, pain, and discomfort.
Research has found proteolytic enzymes to be equal or superior to powerful steroids and nonsteroidal anti-inflammatory drugs, like phenylbutazone, hydrocortisone, indomethacin, and acetylsalicylic acid. Although individual proteolytic enzymes are also useful, their combination doubles the effects.
For decades TMDs have been treated with a lot of options that include physiotherapy and ultrasonography like modalities. ID could be managed by pharmacotherapy and surgically too (either minor or major surgery). We studied the efficacy of oral diclofenac 50 mg in group I patients and a combination of Trypsin 48mg, Bromelain 90mg, Rutoside trihydrate BP 100mg, and Diclofenac sodium 50mg in group II patients. Since these enzymes cause tissue repair and tissue injury or rather a discal injury or inflammation or degeneration is the main feature of ID. This clinical trial found the combination to be very effective.
Our study found a highly significant reduction in pain in both groups on subsequent follow-up. We also found a highly significant difference between pain reductions on the first and second follow-up of groups 1 and 2 patients suggesting group II patients had faster pain relief when compared to group I. We also found patients chewing ability to be improving on subsequent follow-ups in both groups. But group II patients had improved chewing ability faster than group I and it was statistically highly significant too.
Mouth opening improved in both groups on subsequent follow-ups. There was no significant difference in follow-up between the study groups. This probably suggests that even painkillers could sufficiently act on the pain producing substance of masticatory muscles and relieve the mouth opening. We also found the joint noise to be reduced significantly on the second and third follow-up between groups I and II patients. Suggesting enzymes could significantly improve the tissue condition and hence reduce the joint noise. We also found jerky mandibular movements which improved significantly in group II patients when compared to group I patients.
A study by Jayachandran, who studied the effectiveness of oral bromelain, trypsin, rutoside trihydrate enzymes, and diclofenac sodium combination therapy over diclofenac sodium for the treatment of TMJ osteoarthritis, found the combination of painkillers and enzymes to be very effective in osteoarthritis of TMJ.
A study by Akhtar compared the efficacy of oral enzymes with that of diclofenac in patients with osteoarthritis of the knee and they found enzyme combination to be a good alternative than NSAIDs. A review of 10 studies suggests the potential use of Bromelain in treating osteoarthritis. A study by Bolten who evaluated the safety and efficacy of proteolytic enzyme combination in osteoarthritis of the knee found similar pain improvement score in subjects treated with proteolytic enzymes or diclofenac and concluded that proteolytic enzymes were comparable to NSAID diclofenac in relieving pain and increasing functions in adults with osteoarthritis. A study by Klein who compared enzyme therapy with NSAID diclofenac in patients with osteoarthritis found enzyme to be an effective and safe alternative to NSAIDs.
All the above findings suggest use of pain killers along with enzymes for ID of TMJ. Our study found a significant result after the use of this combination for 14 days. All these patients were recalled after 6 months. Only one female patient reported recurrent pain. They were advised regular TMJ exercises and moist heat application and asked to avoid hard food substances for a few months.
Studies related to the use of enzymes for the ID of TMJ are very limited. Only one study till date has reported the benefits of using the above combination in osteoarthritis of TMJ. Rest of the studies have found similar results but the study was done for the knee joint.,,,,, Our study is the first to report the use of proteolytic enzymes in the ID of TMJ in the Indian population. No study so far has reported the use of oral enzymes and its efficacy in ID or disc displacement. The limitation of our study was that the post-treatment recall was of shorter duration, and since this disease is chronic, the longer review period is desirable. Our study would form a basis for more studies on the use of proteolytic enzymes in ID of TMJ with different combinations of proteolytic enzymes with longer review periods.
| Conclusion|| |
ID could be encountered commonly in our day-to-day practice and diagnosing them would not be difficult. But these cases have to be managed well. We recommend the use of a combination of trypsin, bromelain, rutoside, and diclofenac for IDs of TMJ rather than using diclofenac alone.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient (s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Permission from the institutional ethical board was obtained.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Dolwick MF, Katzberg RW, Hams LA. Internal derangement of TMJ: Fact or fiction? J Prosthetic Dent 1983;49: 415-8.
Tatli U, Machon V. Internal Derangements of the Temporomandibular Joint: Diagnosis and Management, Temporomandibular Joint Pathology-Current Approaches and Understanding, Yusuf Emes, Buket Aybar and Gühan Dergin. IntechOpen.doi: 10.5772/intechopen. 72585. Available from: https://www.intechopen.com/books/temporomandibular-joint-pathology-current-approaches -and-understanding/internal-derangements-of-the-temporomandibular- joint-diagnosis-and-management.
Young AL. Internal derangements of the temporomandibular joint: A review of the anatomy, diagnosis, and management. J Indian Prosthodont Soc 2015;15:2-7.
] [Full text]
Kotiranta U, Suvinen T, Forssell H. Tailored treatments in temporomandibular disorders: Where are we now? A systematic qualitative literature review. J Oral Facial Pain Headache 2014;28:28-37.
Dimitroulis G. Management of temporomandibular joint disorders: A surgeon's perspective. Aus Dent J 2018;63 (1 Suppl):S79-90.
Shah D, Mital K. The role of trypsin and chymotrypsin in tissue repair. Adv Ther 2018;35:31-42.
Jayachandran S, Khobre P. Efficacy of bromelain along with trypsin, rutoside trihydrate enzymes and diclofenac sodium combination therapy for the treatment of TMJ osteoarthritis-A randomised clinical trial. J Clin Diagn Res 2017;11:09-11.
Singer F, Singer C, Oberleitner H. Phlogenzyme versus diclofenac in the treatment of activated osteoarthritis of the knee: A double- blind prospective randomized study. Int J Immunotherapy 2001;17:135-4.
Tilwe GH, Beria S, Turakhia NH, Daftary GV, Schiess W. Efficacy and tolerability of oral enzyme therapy as compared to diclofenac in active osteoarthrosis of knee joint: an open randomized controlled clinical trial. J Assoc Physicians India 2001;49:617-21.
Akhtar NM, Naseer R, Farooqi AZ, Aziz W, Nazir M. Oral enzyme combination versus diclofenac in the treatment of osteoarthritis of the knee – a double-blind prospective randomized study. Clin Rheumatol 2004;23:410-15.
Sarah B, George L, Ann W, Hicks SM, Dick M. Bromelain as a treatment for osteoarthritis: A review of clinical studies. Evid Based Complement Alternat Med 2004;1:251-7.
Bolten WW, Glade MJ, Raum S, Ritz BW. The safety and efficacy of an enzyme combination in managing knee osteoarthritis pain in adults: A randomized, double-blind, placebo-controlled trial. Arthritis 2015;2015:251521.
Klein G, Kullich W. Short-term treatment of painful osteoarthritis of the knee with oral enzymes. Clin Drug Invest 2000;19:15-23.
Lotz-Winter H. On the pharmacology of bromelain: An update with special regard to animal studies on dose-dependent effects. Planta Med1990;56:249-53.
Lane L, Jim E. Controlling Inflammation with Proteolytic Enzymes. Nutrition Review.org April 24, 2013;32:142027.
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]