Temporomandibular Joint Injections and Lavage: An Overview of Reviews

Objectives: This overview was conducted following the Preferred Reporting Items for Overviews of Reviews guidelines and aimed to collect and compare the results of systematic reviews on temporomandibular joint injection treatment. Methods: Systematic reviews of randomized clinical trials on temporomandibular disorders treated with lavage or intra-articular administrations were qualified for syntheses. The final searches were conducted on 27 February 2024, without time frame restrictions. Results: Of the 232 identified records, 42 systematic reviews were selected. The most evidence-based conclusions call into question the clinical differences between many therapeutic approaches, including the following: (1) injectable selection for the treatment of pain and hypomobility; (2) the method of performing arthrocentesis; (3) the use of imaging when rinsing the TMJ cavity; (4) the supplementation of the extracapsular administration of unprocessed blood with intracapsular deposition in the treatment of TMJ hypermobility. Conclusions: Systematic reviews based solely on randomized clinical trials proved the following differences: (1) in painful temporomandibular hypomobility, a better therapeutic effect is observed with arthrocentesis followed by I-PRF administration compared to lavage alone; (2) in painful temporomandibular hypomobility, inferior- or double-compartment injection leads to better results than superior-compartment injection; (3) in temporomandibular joint recurrent dislocation, hypertonic dextrose administration is superior to placebo, although (4) unprocessed blood has a better effect than hypertonic dextrose. PROSPERO registration number: CRD42024496142.


Introduction 1.Background
Temporomandibular joints (TMJs) are paired, hidden on both sides under the skin of the preauricular area and under the branches of the facial nerve.A single TMJ consists of the mandibular fossa and the articular tubercle on the temporal bone, which form the acetabulum, and the condylar process of the mandible, which constitutes the articular head.These are separated by an articular disc, which allows for anatomical and functional distinction.All the described structures are surrounded by a joint capsule filled with synovial fluid.Ligaments and muscles provide stability to the above-described structures, as well as causing and limiting jaw movements [1].
Disfunctions of the TMJs or the muscles that move them are called temporomandibular disorders (TMDs).Their average global incident rate is 34% and they more frequently affect women [2].Improper functioning of the articular disc leads to its displacement, which manifests itself acoustically.Gradually progressing with age, degeneration causes the thinning of articular cartilage, followed by erosive and productive changes in the bones.Stopping, and, more importantly, reversing the described processes is considered a current challenge.Complex TMDs therapy involves treatment in the field of psychology, physiotherapy, pharmacotherapy, orthodontics, dental prosthetics, and maxillofacial surgery.The latter is generally reserved for the most severe cases and ranges from injections into the joint cavity to joint replacement [3].The least invasive of the surgical techniques are intracapsular injections.
Injection treatment of TMJs is currently one of the recognized therapeutic techniques.General indications for the use of injection techniques in the treatment of TMJs are Wilkes II-V diagnoses [4].Due to its invasive nature, only patients who have exhausted the less invasive treatment options are typically eligible for injection treatment.Nevertheless, indications for TMJ injections may already occur in adolescence, when juvenile idiopathic arthritis is diagnosed [5].
More and more attention is being paid to aspects of injection therapy other than the type of preparation administered.Differences in the therapeutic protocols proposed by different groups of scientists are significant and include (1) the specific site of deposition (compartments of the joint cavity and pericapsular tissues); (2) the volume of the substance injected; (3) the number of interventions; (4) intervals between interventions [16][17][18][19].
In the case of rinsing the joint cavity, attempts are also made to examine the differences between the following techniques: (1) two-needle; (2) two-way needle; (3) one-way needle (pumping technique) [20][21][22][23][24]. Furthermore, arthrocentesis protocols also differ in terms of the following: (1) the type of irrigant; (2) the volume of the rinsing agent; (3) single use or repetition of the intervention at different time intervals [17,23,25].It is common to combine lavage with active substance administration in one intervention.Finally, it is possible to mix different injectables in one dose.

Rationale
Combining the possibilities mentioned above allows for thousands of configurations of test and control samples.The multitude of injectable substances used, their dosing protocols, and proposals for complex treatment, including arthrocentesis, clearly demonstrate the lack of established therapeutic protocols.The same issues cause difficulties in compiling randomized controlled trials in systematic reviews.However, reviews with a lot of scientific evidence in the discussed field are already being created and provide invaluable assistance to clinicians making therapeutic decisions.

Objectives
This overview of systematic reviews was conducted to summarize the highest quality evidence in the field of temporomandibular joint injections and lavage.

Methods
The overview of reviews was carried out following the "Preferred Reporting Items for Overviews of Reviews (PRIOR), a protocol for the development of a reporting guideline for overviews of reviews of healthcare interventions" [26].The Prospective Register of Systematic Reviews (PROSPERO) registered the review protocol under number CRD42024496142.

Eligibility Criteria
The eligibility criteria are detailed in Table 1.

Information Sources
Medical databases were searched using the Association for Computing Machinery: Guide to Computing Literature, Bielefeld Academic Search Engine, Google Scholar, and National Library of Medicine: PubMed engines [27][28][29][30].The main searches were conducted on 27 July 2023, and updated searches on 27 February 2024.

Search Strategy
The following search strategy was applied: Temporomandibular AND (injection OR injections OR intraarticular OR intra-articular OR intracavitary OR intra-cavitary OR periarticular OR peri-articular OR arthrocentesis OR lavage OR rinse OR rinsing) AND systematic AND review.
Detailed queries adapted to the specificity of search engines are presented in Table A1.

Selection Process
The results were automatically limited using the filters available in search engines (Table A1).Records were then entered into Rayyan's automation tool (Qatar Computing Research Institute, Doha, Qatar and Rayyan Systems, Cambridge, MA, USA), which identified potential duplicates [31].Records were manually deduplicated and blindly screened based on the content of the titles and abstracts (K.C. and M.C.).In cases of the unanimous acceptance of assessments, the given record was promoted to the next stage.The final selection was made based on full-text evaluation (N.T., M.C., and, if necessary, K.C. with a casting vote).The overlapping time frame did not disqualify systematic reviews from further proceedings.

Data Collection Process
Data were independently extracted by two authors (N.T. and K.L.) without using automation tools.In case of discrepancies, they were discussed, and any remaining disagreements were resolved by a third researcher (M.C.).

Data Items
Items necessary to identify the paper (first author, year of publication), characteristics of systematic reviews (coverage dates, number of primary studies and their participants, diagnoses, type of interventions in the study, and control groups), and outcomes (ranges of changes in pain intensity, mandibular abduction, quality of life indices, and qualitative conclusions) were collected.The diagnoses in the areas of internal derangement and isolated osteoarthritis were collectively named TMJ hypomobility to distinguish them from recurrent TMJ dislocation, whose treatment is supposed to have the opposite effect, i.e., limiting the range of mandibular abduction.Generalized arthritis manifesting itself, among others, in the temporomandibular joint area was discussed separately.Data were extracted from the bodies of the reviews and not from the content of the source studies.

Risk of Bias Assessment
The risk of bias in systematic reviews was assessed using the ROBIS tool (K.L. and F.B., and, if necessary, M.C. with a casting vote) [32].ROBIS helps determine the risk of bias in systematic reviews when preparing guidelines and overviews.Assessments were made of the eligibility criteria of the studies, the identification and selection of studies, data collection and the evaluation of studies, synthesis, and the conclusions.[32]

A matrix of comparisons between individual interventions was presented graphically
to illustrate the conclusions supported by randomized controlled trials and areas for further research.

Systematic Review Selection
The search with four engines led to the identification of 232 records (Table A2), of which 124 were rejected in the deduplication process.The remaining 108 abstracts were screened, and 51 were qualified for full-text evaluation.Ultimately, 42 studies were included in the review.The selection process is presented in Figure 1.

Characteristics of Systematic Reviews
Table 2 summarized all thematically consistent systematic reviews.Reviews based solely on randomized controlled trials were promoted to risk of bias assessment and syntheses.

Primary Study Overlap
The overlap in time frames for systematic reviews is presented in Figure 2.

Primary Study Overlap
The overlap in time frames for systematic reviews is presented in Figure 2.

Risk of Bias in Systematic Reviews
The risk of bias was assessed for systematic reviews based on randomized controlled trials and is presented in Table 3. Reviews whose risk of bias was assessed as low were included in the syntheses.

Risk of Bias in Systematic Reviews
The risk of bias was assessed for systematic reviews based on randomized controlled trials and is presented in Table 3. Reviews whose risk of bias was assessed as low were included in the syntheses.

Compared to ultrasound guided AC
No better clinical outcomes (Leung 2020 [50])

Recurrent TMJ Dislocation
Table 6 concerns TMJ recurrent dislocation, also known as TMJ hypermobility.Despite the similar nomenclature, the diagnosis of the latter represents the opposite of hypomobility of the temporomandibular joint.Therefore, there is a separate comparison matrix of the treatment methods, which also differ.In recurrent TMJ dislocation, the treatment is aimed not only at eliminating the pain but also at reducing the mandibular abduction instead of increasing it.

Main Findings
Only HA versus placebo for TMJ hypomobility and HD versus placebo for TMJ hypermobility comparisons were assessed in two systematic reviews each.
Moldez et al. identified three studies (out of the seven included in their systematic review) supporting the statement that the intra-articular administration of HA leads to better results in the treatment of TMJ hypomobility and reduces the associated pain more than a placebo [6].Xie et al. included nine randomized control trials supporting the opposite statement, that the intra-articular administration of HA does not improve pain or maximum mouth-opening compared to placebo administration [12].Both systematic reviews were rated as having a low risk of bias in this overview.The inconsistent results of the two independent systematic reviews encourage further primary research.Attention should also be paid to the details of the HA administration protocol, such as the presence of a preceding lavage, the number of injections, and the length of the intervals between interventions.In addition, the type and amount of HA preparation are worth considering.These issues are already being raised in individual clinical studies, but the paucity of material makes it challenging to undertake appropriate syntheses.
Both Sit et al. and Nagori et al. proved that intra-articularly administered HD was significantly more effective than placebo in TMJ recurrent dislocation [15,48].The report by Sit et al. was based on ten randomized control trials [48].Nagori et al. qualified three studies with the same level of evidence [15].Both systematic reviews were rated as low-risk.This suggests consensus among researchers that intra-articular HD injections resolve pain and reduce TMJ hypermobility better than placebo.The time frames of the discussed reviews overlap, which cannot be underestimated.

AC in TMJ Hypomobility
AC with a small volume of lavage fluid (less than 150 mL) is as effective, if not more, as a high-volume procedure [17].A USG-guided AC does not lead to a better outcome than an unguided intervention [50].Combining AC with the administration of CS does not provide any superior effect compared to AC alone [54].Sole TMJ rinsing was proved to have an inferior effect compared to AC followed by I-PRF administration [36].Combining AC with HA led to similar effects to combining it with I-PRF [62].

CS in TMJ Hypomobility
The effect of the intra-articular administration of CS in TMJ hypomobility cases does not differ from that of the placebo control.It does not provide an advantage in terms of pain relief and TMJ mobility [12].Another systematic review revealed no significant differences between the intra-articular administration of CS and HA [6].

HA in TMJ Hypomobility
The advantage of using HA compared to a placebo is questionable.It was demonstrated in one systematic review and denied in another [6,12].Moreover, HA administration also showed no significant difference compared to CS [6].

PRP in TMJ Hypomobility
The intra-articular administration of PRP was proved to provide no better outcomes than using a placebo [12].

Local Anesthetics in TMJ Hypomobility
The advantage of using bupivacaine over placebo was observed in the first 24 h of follow-up only [11].In more extended observations, local anesthetics do not provide a better effect than a placebo.

Different Compartment Injections in TMJ Hypomobility
Injection into the superior compartment only was less efficient than inferior-or doublecompartment injections.This conclusion is also supported by a more recent systematic review based on primary studies with varying levels of evidence [16,18].

Limitations of the Overview Methods
Only papers in English were included.

Strengths of the Overview
The strengths of this overview are the unlimited time frame, the low risk of bias in the assessment of source reports, and the conclusions, which were based solely on systematic reviews of randomized clinical trials.

Implications
The identified evidence suggests that some procedures can be simplified without loss to the patient, which may make treatment easier, faster, and cheaper.The use of low-volume, non-imaging arthrocentesis for painful limitations of mandibular mobility and exclusively using the extracapsular deposition of autologous unprocessed blood for habitual TMJ luxation should be considered.On the other hand, some additional measures were proven to be valid.In cases of limited jaw mobility, the administration of I-PRF after arthrocentesis and injections into the less accessible lower TMJ compartment seem to be justified.

Conclusions
In painful temporomandibular hypomobility, a better therapeutic effect is observed with injectable platelet-rich fibrin administration preceded by arthrocentesis than when using arthrocentesis alone.For the same diagnosis, inferior-or double-compartment injection leads to better results than superior-compartment deposition.In temporomandibular joint recurrent dislocation, hypertonic dextrose administration is superior to placebo but inferior to unprocessed autologous blood.

Figure 2 .
Figure 2. Overlap of primary studies in systematic reviews.

Figure 2 .
Figure 2. Overlap of primary studies in systematic reviews.

Table 3 .
Risk of bias in systematic reviews.

Table 3 .
Risk of bias in systematic reviews.

Table 5 .
Comparison matrix of systematic review conclusions regarding injection techniques in TMJ hypomobility.

Table 6 .
Comparison matrix of systematic review conclusions regarding recurrent TMJ dislocation.

Table A2 .
Identified and filtered records.