Intra-articular injections with corticosteroids and sodium hyaluronate for treating temporomandibular joint disorders : A systematic review

Conclusion: After analyzing the literature, it was found that intra-articular injection with corticosteroids and sodium hyaluronate seems to be an effective method for treating internal derangements of the TMJ. However, further randomized controlled clinical trials, with representative samples and longer follow-up time must be carried out in order to assess the real effectiveness of this technique.


INTRODUCTION
The condyle/articular disc complex incoordination is among the temporomandibular joint disorders.It results from the collapse regarding the normal function of the disc on the condyle and it is due to disc collateral ligaments incompetence and lower retrodiscal plate.Examples of this case are disc displacements with and without reduction which may be associated with inflammatory changes such as capsulitis, synovitis and retrodiscitis or with degenerative changes such as osteoarthritis and osteoarthrosis of the Temporomandibular Joint (TMJ). 1 The protocols for initial treatment consists of choosing reversible and little invasive therapies, such as occlusal splints, non-steroidal anti-inflammatory drugs (NSAID), analgesics, physiotherapy, thermotherapy, microcurrent, functional repose and patient advice.However, in some cases, conservative treatment becomes little responsive due to current structural changes. 1 Thus, more complex procedures such as intra-articular injections with corticosteroids or sodium hyaluronate, arthrocentesis, arthroscopy or open surgery for TMJ appear as therapeutic options to control and treat TMJ internal derangements.
In such cases, intra-articular injections with corticosteroids and sodium hyaluronate -the hyaluronic acid sodium salt, a clinical procedure known as viscosupplementation -appear as an alternative of a treatment that is less invasive than surgical procedures for TMJ.Thus, this study aimed at analyzing, through a systematic literature review and within the context of an evidence-based Dentistry, the effectiveness of intra-articular injections with corticosteroids and sodium hyaluronate as a treatment for TMJ internal derangements.

MATERIAL AND METHODS
We carried out a computerized research in the following databases: MEDLINE, Cochrane, EMBASE, Pubmed, Lilacs and BBO, considering publications issued between 1966 and October of 2010.The research descriptors comprised terms widely used within the line of research proposed by this study.The research descriptors used were "corticosteroids", "hyaluronic acid", "sodium hyaluronate", "temporomandibular disorder," "temporomandibular joint", "craniomandibular disorder", "tmd", "tmj", "osteoarthritis" and "osteoarthrosis", which were crossed in search engines.The initial list of articles, evaluated by their title and abstract, was submitted to review carried out by two appraisers who applied inclusion criteria hereinbelow to determine the final sample of articles.Should there have been any discrepancy between the results obtained by the reviewers, a third appraiser would be consulted and requested to read the full version of the article.
The inclusion criteria for selecting the articles were:

RESULTS
The initial list of articles comprised 412 possible studies.After applying the inclusion criteria, we obtained 9 randomized controlled clinical trials, 7 of which were double-blind and 2 single-blind, as shown in Figure 1.Kappa coefficient between reviewers was of 1.00 and the results of the selected studies are presented in Tables 1 and 2.

DISCUSSION
The qualification of the generated scientific evidence is related to the methodological criteria and the designs adopted by the authors in the clinical studies.Thus, criteria such as randomization, blinding, sam-ple size calculation, calibration, control of involved factors, among others, aimed at making scientific evidence more precise and reliable and this information should be provided in order to facilitate readers' appreciation and discussion of the scientific article. 11,12urthermore, knowledge about the study designs which generate the highest levels of evidence must be of common knowledge: meta-analysis, systematic reviews and randomized clinical trials.The results of this systematic review show that many of the selected studies had small samples and short follow-up periods.In addition, the results highlight the absence of a universal and standardized method for diagnosing TMD which hampers comparison between clinical trials.In this systematic review, different authors used different indexes for diagnosing TMD: RDC/TMD, 25 Helkimo index, 26,27 adaptations of these or other criteria, highlighting the necessity of further randomized controlled clinical trials using universal, standardized and valid index in representative samples and with a longer follow-up period.
According to the studies included in accordance with the methodological criteria of this systematic review, significant scientific evidence demonstrates that viscosupplementation with sodium hyaluronate is an effective treatment for TMJ internal derangements at short 2,3,6 and medium 4,5,7 terms, with results that are similar 2,3,6 or greater 7 than the ones obtained by corticosteroids intra-articular injections.Furthermore, combining SH with arthrocentesis brought major improvements after surgery, greater than those obtained by the group that did not receive SH. 10 On the other hand, combining or not SH with arthroscopy did not show any statistically significant differences. 9Some limitations can be associated with some of this evidence: Small samples, 2,3 short follow-up time 2,3,6,9 and lack of information on how many patients were lost or drop-out during the study. 4,9,10Such limitations reduce the power of the scientific evidence generated.
Other clinical studies assessing viscosupplementation with sodium hyaluronate, which present good evidence level, but were not included in this systematic review due to some issues concerning the criteria of randomization 28 or blinding, 29,30 indicate symptoms reduction and functional improvements in cases with joint TMD, with results that lasted during follow-up. 28,29,30Evaluations of SH intra-articular injections protocols showed results statistically equivalent to therapy carried out with occlusal splints for 6 months. 28omputed tomography examinations, which proposed to assess changes in osteoarthritic TMJ due to intra-articular injections, show that progression, regression and absence of changes in cases with Hyaluronic acid (HA) is a mucopolysaccharide acid present in ground substance animal tissues.It is the major component of the synovial fluid and has an important role in lubrication, nutrition, homeostasis and load absorption of articular tissues. 13,14,15In cases of inflammatory and degenerative changes of joints, the concentration and molecular weight of HA id reduced. 16,17Viscosupplementation with sodium hyaluronate increases the concentration and molecular weight of HA in the synovial fluid, 18 restoring tissues lubrication and nutrition as well as minimizing mechanic stress. 15,19Moreover, intra-articular SH injection presents an analgesic effect by blocking receptors and endogenous substances that cause pain in synovial tissues.In addition, it promotes a release of adhesion areas between the articular disc and the mandibular fossa, increasing joint mobility and allowing better synovial fluid circulation. 19t first, the intra-articular sodium hyaluronate injection was used in race horses with traumatic arthritis. 20Afterward, it was based on studies on the osteoarthritis model, induced in animals, and combined with the inhibition of osteoarthritis development. 21In the mid-70's, viscosupplementation with sodium hyaluronate began to be used in humans for osteoarthritis treatment of large joints such as knee, hip and shoulder, 22 being indicated for the internal derangements of TMJ after 1979. 23lucocorticoids are yet the most effective anti-inflammatory drugs available, promoting symptomatic improvements of a series of clinical manifestations.However, they present risks of potential adverse effects which affect several organs depending on the dosage and, mainly, the duration of the treatment.For short periods (up to two weeks), even at high doses, the probability of causing adverse side effects is low.In long-term treatments, serious side effects appear, limiting the effectiveness of glucocorticoids in chronic diseases.Glucocorticoids have a very original mechanism of action, essentially genomic (transcriptional) and characterized by the activation (transactivation) or inhibition (transrepression) of numerous target genes.These molecules act in many cells, including not only innate immunity cells (macrophages, granulocytes, mast cells) and adaptive immunity cells (lymphocytes), but also other cells (fibroblasts, epithelial and endothelial cells). 24ntra-articular injections with corticosteroids and sodium hyaluronate for treating temporomandibular joint disorders: A systematic review original article osteoarthritis are observed in TMJ that have been treated and in contralateral TMJ that have not been treated, showing no statistically significant differences between sodium hyaluronate and corticosteroid. 8oreover, they highlight the importance of assessments carried out by imaging examinations associated with clinical criteria in order to analyze the progression or regression of TMJ osteoarthritis.
The accomplishment of further randomized controlled clinical trials, with representative samples and longer follow-up periods, shall enable not only the evaluation concerning the real effectiveness of corticosteroids and sodium hyaluronate, but also the obtainment of an objective protocol for using them.This technique seems to perform well in refractory situations regarding conservative treatments, arthralgias with limitation of movement and/or severe joint sounds, arthralgia associated with moderate and severe degenerative changes and in cases of movement limitation caused by disc displacement without reduction and adhesions.
At first, in cases of temporomandibular disorders, the focus must be noninvasive, conservative and reversible, making use of therapeutics such as occlusal splints, pharmacotherapy, physiotherapy, thermotherapy, microcurrent, functional rest, and patient advice.In those cases in which conservative treatment is not responsive, corticosteroids and sodium hyaluronate intra-articular injections appear as a non-surgical, low invasive and safe alternative which is associated with good results at short and medium terms when treating internal derangements of TMJ.
With regard to the orthodontic specialty, it is important to consider knowledge based on evidence and relative to the action mechanisms and clinical applications of many different therapeutic options for TMD patients, so that the orthodontist and the patient are aware of the therapeutic option regarding the intraarticular injections with corticosteroids and sodium hyaluronate as well as its safety and efficacy in refractory cases concerning conservative treatment.

CONCLUSIONS
» According to randomized controlled clinical trials, the intra-articular injections with corticosteroids and sodium hyaluronate seem to be an effective method to control TMJ internal derangements at short and medium terms.» In short-term treatments, the effects of intraarticular injections with sodium hyaluronate are similar to those regarding the injections with corticosteroids, while in long-term treatments, injections with sodium hyaluronate showed better results.» Further randomized controlled clinical trials with representative samples and long followup times are necessary to assess the real effectiveness of the intra-articular injections with corticosteroid and sodium hyaluronate technique and to establish an objective protocol.
Intra-articular injections with corticosteroids and sodium hyaluronate for treating temporomandibular joint disorders: A systematic review original article

Table 1 -
Studies included in the research and which compare corticosteroids, sodium hyaluronate, and placebo.

Table 2 -
Studies included in the research and which compare arthrocentesis or arthroscopic followed or not by injection with corticosteroid and/or sodium hyaluronate.