Estudio comparativo entre tratamiento con infiltraciones intraarticulares de betametasona, hialuronato de sodio y plasma rico en plaquetas en pacientes con artralgia de la articulación temporomandibular

Laburpena

Introduction: Temporomandibular disorders (TMD) or Craniomandibular dysfunction are collective terms that cover a wide spectrum of clinical problems of the tempormandibular joint and the masticatory muscles in the orofacial area. These dysfunctions are mainly characterized by pain, sounds in the joint and limited and irregular function of the jaw. TMD are considered a subgroup apart from musculoskeletal and rheumatic disorders, and represent a major cause of orofacial pain of non-dental origin. (1-3). Temporomandibular disorders are highly prevalent in the general population. According to several studies, and based on the populations studied, the rates and criteria used for the diagnosis, the prevalence of TMD varies from 16 to 45 per cent of the population. (4,5) It is widely accepted that temporomandibular disorders are a group of highly prevalent, often poorly or late diagnosed pathologies which mainly affect adults, young people and women. The temporomandibular joint (TMJ) is the joint that connects the mandible through its condyle to the temporal bone of the skull. It is in an anterior position of the ear bilaterally and is highly significant, because it is responsible for the movements of the mouth and, therefore, chewing, phonation and facial expression. It is a joint with very special characteristics, but obviously has a similar behavior to that of other joints in our body. The etiology of temporomandibular disorders is complex and multifactorial. Biomechanical, neuromuscular, biopsychosocial and biological factors may be present. On the other hand, under different circumstances, there are individual factors that interfere with an individual's risk of developing or not developing dysfunction. Data from the National Health Interview Survey show that 5% of the US population reported orofacial pain in the last 3 months. Other studies have shown that Temporomandibular disorders are essentially a condition affecting young and middle-aged people, to the detriment of children and the elderly, and is approximately twice more common among women than in men. (6) According to Diagnostic Criteria for Temporomandibular Disorders (DC/TMD), the TMD can be divided into three large groups: the muscular group, disc displacements and osteoarthritis/osteoarthritis. The success of any treatment requires a correct diagnosis and all treatment plans must take into account the patient's individual needs and expectations for correct outcomes. A transversal therapeutic attitude to almost all types of TMD is cognitive-behavioral therapy and muscle relaxation measures. (7-10) There is still a great variety of treatments that we must choose depending on each case and patient. The most important are: cognitive behavioral therapy, physical therapy, dry needling, occlusal adjustments, surgery, bite splints, pharmacotherapy, and intraarticular injections that were the object of this study. The products administered were Betamethasone, sodium hyaluronate and platelet-rich plasma. Intraarticular drug injections are a common therapy, mainly in orthopedic and/or rheumatological disorders associated with pain, and cartilaginous, bone and joint capsule inflammation, as well as fibrous adhesions. Intraarticular infiltrations with corticosteroids have been used with very good results for the treatment of different temporomandibular joint pathologies (11-15), despite the presence of some adverse effects such as the progression of a pre-existing joint injury (13). Sodium hyaluronate, a high molecular weight polysaccharide, which is a sodium salt of hyaluronic acid, a physiological component of the synovial fluid, responsible for joint lubrication, has also been used in the temporomandibular joint, either to promote increased viscosupplementation or as anti-inflammatory, and the results have been very promising (12,13,16-20). Platelet-rich plasma is a therapeutic agent composed of a platelet concentrate and associated growth factors, taken and centrifuged from a patient's own blood sample. It was initially introduced in the field of Dentistry/Oral and Maxillofacial Surgery/ Plastic and Reconstructive Surgery in the 90's, and their clinical use is due to its wound healing properties potentially by the recruitment, proliferation, and differentiation of cells and, therefore, tissue remodeling. (21-23) Material and Methods: Patients: A sample of 80 patients who had been diagnosed with TMJ arthralgia according to the original version of the diagnostic criteria for temporomandibular disorders (DC/TMD) was recruited from consultations framed in the Course of Occlusal Rehabilitation at the University of Coimbra organized by the School of Medicine at the said university (FMUC). All of them agreed to participate in the research and signed the informed consent form. This study was conducted in compliance with the Declaration of Helsinki and was approved by the ethics committee of the School of Medicine of the University of Coimbra (Coimbra, Portugal). Inclusion criteria: Patients who met all the following requirements were included in the study: a clinical history of over 6 months of TMJ pain that modifies with mandibular movement in function or parafunction; pain present in clinical examination at opening, laterality or palpation and no previous treatment. Exclusion criteria: - Patients who had received previous treatment for temporomandibular disorders. -Patients suffering from any rheumatic pathology such as rheumatoid arthritis, psoriatic arthritis, and juvenile arthritis, pregnant or breastfeeding women - Patients who were under 18 years old. Patients were randomly assigned to four groups, each of them including 20 patients (n=20): patients receiving bite splint therapy only (BS); patients using a bite splint and receiving betamethasone (BS+B); patients using a bite splint and treated with sodium hyaluronate (BS+SH); and patients using a bite splint and undergoing PRP treatment (BS+PRP). Treatments: A bite splint was made for each patient, with contact points in all teeth and canine guidance in laterality and protrusion movements. The splints were worn during the night and the occlusal readjustment visits took place with the following periodicity: one week, two weeks, one month after the beginning of treatment, and thereafter every month. The control group was made up of patients who were treated with bite splint therapy only. For groups BS+B and BS+HS, in addition to the bite splint, the following protocol was followed: after disinfection of the pre-auricular area, they were injected with 1 ml of articaine (40mg/ml) and adrenaline (10µg/ml). A 23 gauge needle was used to inject 1 ml of betamethasone – (Diprofos Depot 7 mg/ml) or 1 mL of sodium hyaluronate - Hyalart 10 mg/mL. The exact puncture point was determined by drawing the canthal-tragus line and measuring 10 mm from the tragus and 2 mm below the line. The zygomatic arch was palpated and the patient was asked to open his mouth to move the condyle anteriorly. The position of the needle should be from the outside in, from top to bottom and from back to front. Patients were evaluated one week after the beginning of the treatment, one month later and six months later and were informed that they could experience discomfort in the region. In the BS+PRP group, the injections were preceded by the collection of the patient's peripheral blood from the ulnar vein into a glass tube with sodium citrate as an anticoagulant. After mixing the blood with the citrate using rotating movements, the tubes were centrifuged at 3200 rpm for 12 minutes. After careful aspiration of platelet-rich plasma into a syringe, 2mL of PRP were injected into the TMJ following the previously described procedure for BS+B and BS+HS injections. Pain and mouth opening measurements Pain was evaluated using a visual analogue scale. In brief, this method consists of a 10-cm line that represents the continuous spectrum of the painful experience: the left end means "no pain" and the right "the worst pain imaginable." On this scale, patients must indicate the degree of pain they feel. Values range from 0 to 10, where 0 is no pain, 1-3 a little, 4-7 much, and 8-10 unbearable. To assess the mouth opening variable, a ruler was used to measure the distance between incisors and the results were entered in an Excel datasheet. Statistics The descriptive statistics of the demographic data were carried out according to the groups studied. Gender was described in terms of absolute and relative frequency and age using the mean and standard deviation from the mean. Differences between groups were assessed using repeated ANOVA measurements with an independent factor. Subsequently, linear regression was adjusted to each group to compare the yield of each curve. Statistical analysis was carried out on the IBM SPSS v24 platform adopting a significance level of p<0.05. Results Patient description The average age of the sample population was of 43.1 ± 17.7, whereas gender proportion was 20% men and 80 % women. Gender distribution and age in the treatment groups yielded no significant differences. Treatment BS BS+B BS+SH BS+PSP Gender (M/W) 4/16 (20%/80%) 4/16 (20%/80%) 4/16 (20%/80%) 4/16 (20%/80%) Age (x ̅ ±SEM) 41.3 ± 4 40.8 ± 3.7 37.4 ± 3.1 36.7 ± 2.9 Treatments to reduce pain The aim of the study was to test whether the different applied treatments could reduce pain and improve mouth opening in patients with TMDs. Thus, pain intensity was analysed at 1 week, 1 month and 6 months after the intervention. There were no differences in pain intensity among the groups at the beginning of the study. However, we found that at all these points after beginning therapy there was a highly significant pain reduction (p<0.01). Subsequently, regression analysis evaluating pain variation over time showed that pain decreased significantly in all the groups treated with injections [(3.75)=402.6; p<0.001)], a decrease that was lower in the bite splint group, with an average rate of 0.05 values in the pain scale per week, and higher in the splint+PRP group, with an average rate of 0.172 values per week. Regression analysis values are shown in the table and figure below. Pain values Regression analysis Group Start 1 week 1 month 6 months p R2aj B [IC95%] BS 6.4 ± 0.5 4.8 ± 0.7 4.3 ± 0.7 4.3 ± 0.7 0.128* 0.017 0.219 [-0.065; 0.503] BS+B 7.1 ±0.4 2.5 ± 0.4 1.4 ± 0.4 0.7 ± 0.3 0.001 0.219 0.546 [0.316; 0.776] BS+SH 5.8 ± 0.5 1.6 ± 0.5 1.4 ± 0.5 0.9 ± 0.5 0.001 0.204 0.418 [0.237; 0.598] BS+PRP 5.9 ± 0.6 3.3 ± 0.5 1.9 ± 0.4 0.2 ± 0.1 0.001 0.372 0.676 [0.482; 0.871] Data are shown as mean±SEM. BS: Bite splint; BS+B: Bite splint and betamethasone; BS+SH: Bite splint and sodium hyaluronate; BS+PRP: Bite splint and plasma-rich platelet. R2aj: Adjusted coefficient of determination; B: regression coefficient.* The fact that the bite splint group’s model has not been statistically significant could be due to the large dispersion of observed values. Treatments to increase mouth opening Next, variations in patients’ maximum mouth opening over time with the different treatments were analysed. At the beginning of the treatment, there were no significant differences regarding mouth opening capacity. Subsequently, according to our linear correlation analysis, mouth opening increases over time in a significant way in all four groups [F(3.75)=7,874; p<0.001)], this being smaller in the bite splint group and larger in the splint+PRP group, as shown by the regression coefficients. Mouth opening values (mm) Regression analysis Group Start 1 week 1 month 6 months p R2aj B IC95% BS 26.8±2.3 32.8±2.6 34.7±3.0 35.6±2.9 0.128 0.017 0.129 [-0.065; 0.503] BS+B 22.2±2.1 37.1±1.9 40.6±1.3 43.6±1.2 <0.001 0.219 0.546 [0.316; 0.776] BS+SH 26.1±1.6 40.3±1.3 41.7±1.0 44.0±0.7 <0.001 0.204 0.418 [0.237; 0.598] BS+PRP 25.8±2.0 33.6±2.0 39.5±1.6 46.8±0.5 <0.001 0.372 0.676 [0.482; 0.871] Data are shown as mean±SEM in mm. BS: Bite splint; BS+B: Bite splint and betamethasone; BS+SH: Bite splint and sodium hyaluronate; BS+PRP: Bite splint and plasma-rich platelet. R2aj: Adjusted coefficient of determination; B: regression coefficient. Therefore, mouth opening gradually increases over time, being lower in the bite splint group with an average rate of 0.219 per week, and higher in the splint+PRP group with an average rate of 0.676 per week. Based on these data and according to this study, we can confirm that all four treatments succeed in reducing pain intensity and in improving mouth opening over time. Discussion: The aim of this research was to assess the effectiveness of treatment with intra-articular injections of betamethasone, hyaluronic acid and platelet-rich plasma in combination with the nocturnal use of a bite splint compared with the isolated use of the splint. The data analysed were maximum unaided and painless mouth opening (distance measured in millimetres) and pain intensity using a 0 to 10 visual analogue scale. Whereas there is evidence of the effectiveness of bite splint therapy, there is much debate around the kind of oral devices that should be used (24) and around the use of intra-articular injections of betamethasone, hyaluronic acid, and platelet-rich plasma (11-15,25-27). All the patients were evaluated on the day the treatment was started, one week later, one month later and six months later. Our results agree with other studies where similar methodologies were applied (28-30). Bite splint therapy is among the four therapeutic approaches included in this study, being the most common and long-term treatment used worldwide for patients with TMD, yielding favourable responses in many patients and reporting low rates of failure (31) In this study, the group that only used the bite splint was the one that showed the least improvement compared to their initial condition in terms of maximum mouth opening and reduction in pain intensity. Regarding pain, values started at an average of 6.4 and ended with 4.3 after six months, which represents an average decrease of 0.05 per week, the most marked period of pain reduction taking place, precisely, in the first week, with an average value of 4.8. Regarding mouth opening, the results are very similar to those obtained for pain intensity, beginning from an average value of 26.8 mm and ending with 35.6 mm. Thus, a 6-mm increase in the mean was achieved at the end of the first week. Concerning the combined treatment of splint and betamethasone and splint and hyaluronic acid infiltration, several studies report similar results in the treatment of TMJ arthralgia. However, it is very difficult to establish a comparison with this research because almost all the studies use such technique as complementary to a more invasive one such as arthrocentesis (26,27,32). In this work, we found that treatment with sodium hyaluronate and betamethasone reported similar effectiveness. In terms of pain intensity, they initially reported an average of 5.8 and 7.1, respectively, the final values being 0.7 and 0.9, with both groups experiencing a drastic decrease in pain over the first week. Similarly, maximum mouth opening values started at 26.1 for sodium hyaluronate and at 22.2 for betamethasone, and after six months, very close values of 44 and 43.6 mm were reached, which are within normal opening values. The results revealed a better response to platelet-rich plasma treatment than to the previously commented therapies. First of all, it is important to mention that there are few studies involving the use of platelet-rich plasma in the treatment of TMJ arthralgia followed or not by arthrocentesis. However, a recent systematic review shows encouraging results for the use of platelet-rich plasma against other therapeutic approaches (32). In this study, the group that received platelet-rich plasma intra-articular injections benefited most of the four groups studied, starting from pre-treatment pain intensity values of 5.9 and obtaining mean values of 0.2 after six months of treatment, which means that values decreased by 0.172 each week. Patients also started with maximum mouth opening values of 25.8 mm that improved to 46.8 mm. However, it should be noted that, although there was a decrease in pain intensity over the first week to a value of 3.3 and an increase in unaided mouth opening to 33.6 mm, these values fall behind those obtained for sodium hyaluronate and betamethasone. Conclusions: From the analysis of the results presented and based on the sample of this research, it can be concluded that: All treatment models used show significant improvement in both the maximum painless mouth opening and pain intensity. The platelet-rich plasma + bite splint treatment was the one that gave the best results after six months. On the other hand, the use of the bite splint isolated was the option with less significant improvements. The treatments in which an infiltration an of betamethasone or hyaluronate sodium is added to the use of the bite splint have a very similar behaviour over the six months, and the patients improved more in the first week after the start of treatment in comparison with the other groups. To understand the maintenance of the results, it is necessary to continue to monitor these patients and to carry out other similar studies. References: 1. LeResche L, Mancl L, Sherman JJ, Gandara B, Dworkin SF (2003) Changes in temporomandibular pain and other symptoms across the menstrual cycle. Pain 106:253– 261. 2. Goldstein BH. Temporomandibular disorders. A review of current understanding.Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999;88:379- 85. 3. Okeson JP. Orofacial pain: guidelines for assessment, diagnosis, and management. Carol Stream: Quintessence, 1996. 4. Dworkin SF, Le Resche L. Research diagnostic criteria for temporomandibular disorders: Review, criteria, examinations and specifications, critique. J Craniomandib Disord 1992;6:301-355. 5. Manfredini D, Guarda-Nardini L, Winocur E, Piccotti F, Ahlberg J, Lobezoo F. Research diagnostic criteria for temporomandibular disorders: A Systematic review of axis I epidemiologic findings. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2011;112:453-462. 6. Maixner W, Fillingim Rb, Williams DA, Smith SB, Slade GD. Overlapping chronic pain conditions: Implications for diagnosis and classification. J Pain 2016; 17(suppl 9):T93-T107. 7. Fischer DJ, Mueller BA, Critchlow CW, LeResche L. The association of temporomandibular disorder pain with history of head and neck injury in adolescents. J Orofac Pain. 2006;20:191198. 8. Klobas L, Tegelberg A, Axelsson S. Symptoms and signs of temporomandibular disorders in individuals with chronic whiplash-associated disorders. Swed Dent J. 2004;28:29-36. 9. Miyake R, Ohkubo R, Takehara J, Morita M. Oral parafunctions and association with symptoms of temporomandibular disorders in Japanese university students. J Oral Rehabil. 2004;31:518-523. 10. Winocur E, Gavish A, Finkelshtein T, Halachmi M, Gazit E. Oral habits among adolescent girls and their association with symptoms of temporomandibular disorders. J Oral Rehabil. 2001;28:624-629. 11. Kopp S, Wenneberg B. Effects of occlusal treatment and intraarticular injections on temporomandibular joint pain and dysfunction. Acta Odontol Scand. 1981;39:87–96. 12. Kopp S, Carlsson GE, Haraldson T, Wenneberg B. Long-term effect of intra- articular injections of sodium hyaluronate and corticosteroid on temporomandibular joint arthritis. J Oral Maxillofac Surg. 1987;45:929–935. 13. Kopp S, Akerman S, Nilner M. Short-term effects of intraarticular sodium hyaluronate, glucocorticoid, and saline injections on rheumatoid arthritis of the temporomandibular joint. J Craniomandib Disord Facial Oral Pain. 1991;5:231– 238. 14. Wenneberg B, Kopp S, Grondahl H-G. Long-term effect of intra-articular injections of a glucocorticosteroid into the TMJ: a clinical and radiographic 8-year follow-up. J Craniomandib Disord Facial Oral Pain. 1991;5:11–18. 15. Alstergren P, Appelgren A, Appelgren B, Kopp S, Lundeberg T, Theodorsson E. The effect on joint fluid concentration of neuropeptide Y by intra-articular injection of glucocorticoid in temporomandibular joint arthritis. Acta Odontol Scand. 1996;54:1–7. 16. McCain JP, Balazs EA, de la Rua H. Preliminary studies on the use of a viscoelastic solution in arthroscopic surgery of the temporomandibular joint. J Oral Maxillofac Surg. 1989;47:1161–1168. 17. 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 Rehabil. 2002;29:80–86. 18. Guarda-Nardini L, Tito R, Staffieri A, Beltrame A. Treatment of patients with arthrosis of the temporomandibular joint by infiltration of sodium hyaluronate: a preliminary study. Eur Arch Otorhinolaryngol. 2002;259:279–284. 19. Guarda-Nardini L, Masiero S, Marioni G. Conservative treatment of temporomandibular joint osteoarthrosis: intra-articular injection of sodium hyaluronate. J Oral Rehabil. 2005;32:729–734. 20. Yeung RWK, Chow RLK, Samman N, Chiu K. Short-term therapeutic outcome of intra-articular high molecular weight hyaluronic acid injection for nonreducing disc displacement of the temporomandibular joint. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006;102:453–461. 21. Anitua E, Andia I, Ardanza B, Nurden P, Nurden AT. Autologous platelets as a source of proteins for healing and tissue regeneration. Thromb Haemost 91:4–15,2004. 22. Frank C, McDonald D, Shrive N. Collagen fibril diameters in the rabbit medial collateral ligament scar: a longer term assessment. Connect Tissue Res 36:261– 269,1997. 23. Marx RE. Platelet-rich plasma: evidence to support its use. J Oral Maxillofac Surg 62:489–496,2004. 24. Klasser GD, Greene CS. Oral appliances in the management of temporomandibular disorders. Oral Surgery, Oral Med Oral Pathol Oral Radiol Endodontology. 2009;107:212–23. 25. Marzook HAM, Abdel Razek AA, Yousef EA, Attia AAMM. Intra-articular injection of a mixture of hyaluronic acid and corticosteroid versus arthrocentesis in TMJ internal derangement. J Stomatol oral Maxillofac Surg. 2019; 26. Moldez MA, Camones VR, Ramos GE, Padilla M, Enciso R. Effectiveness of Intra-Articular Injections of Sodium Hyaluronate or Corticosteroids for IntracapsularTemporomandibular Disorders: A Systematic Review and Meta-Analysis. J oral facial pain headache. 2018;32:53–66. 27. Zotti F, Albanese M, Rodella LF, Nocini PF. Platelet-Rich Plasma in Treatment of Temporomandibular Joint Dysfunctions: Narrative Review. Int J Mol Sci. 2019;20:277. 28. Vingender S, Restár L, Csomó KB, Schmidt P, Hermann P, Vaszilkó M. [Intra-articular steroid and hyaluronic acid treatment of internal derangement of the temporomandibular joint]. Orv Hetil. 2018;159:1475–82. 29. Hegab AF, Ali HE, Elmasry M, Khallaf MG. Platelet-Rich Plasma Injection as an Effective Treatment for Temporomandibular Joint Osteoarthritis. J Oral Maxillofac Surg. 2015;73:1706–13. 30. Goiato MC, da Silva EVF, de Medeiros RA, Túrcio KHL, dos Santos DM. Are intra-articular injections of hyaluronic acid effective for the treatment of temporomandibular disorders? A systematic review. Int J Oral Maxillofac Surg. 2016;45:1531–7. 31. R. Civinini, A. Macera, L. Nistri, B. Redl, and M. Innocenti, “The use of autologous blood-derived growth factors in bone regeneration,” Clinical Cases in Mineral and Bone Metabolism, vol.8,no.1,pp.25–31,2011. 32. Goa KL, Benfield P. Hyaluronic acid. A review of its pharmacology and use as a surgical aid in ophthalmology, and its therapeutic potential in joint disease and wound healing. Drugs 1994; 47: 536-566.