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Arthrocentesis with or without additional drugs in temporomandibular joint inflammatorydegenerative disease: comparison of six treatment protocols

J o u r n a l o f Oral Rehabilitation Arthrocentesis with or without additional drugsin temporomandibular joint inflammatory-degenerativedisease: comparison of six treatment protocols* D . M A N F R E D I N I , D . R A N C I T E L L I , G . F E R R O N A T O & L . G U A R D A - N A R D I N I TMDClinic, Department of Maxillofacial Surgery, University of Padova, Padova, Italy SUMMARY The aim of the present pilot investigation improvement with respect to mean baseline values was to compare the effectiveness of six treatment was recorded in all the five treatment groups com- protocols providing temporomandibular joint (TMJ) pleting the protocol. No significant differences arthrocentesis with or without additional drugs to emerged between groups in any outcome variable.
manage symptoms in patients with inflammatory- The protocol providing five sessions of two-needle degenerative TMJ disease. A consecutive series of 72 arthrocenteses plus low molecular weight HA patients with TMJ osteoarthritis (axis group IIIb) allowed achieving the highest improvement in with pain lasting from more than 6 months were almost all the outcome variables. Findings suggested randomly assigned to one of the groups receiving that no statistically significant differences existed the following treatment protocols: single-session between the treatment groups. The clinical signifi- cance of these findings needs to be tested with two-needle arthrocentesis plus corticosteroid (B), future studies on larger samples with longer follow- single-session two-needle arthrocentesis plus low molecular weight hyaluronic acid (HA) (C), single- KEYWORDS: temporomandibular disorders, temporo- mandibular joint, arthrocentesis, hyaluronic acid, molecular weight HA (D), 5 weekly two-needle arthrocenteses plus low molecular weight HA (E) and 5 weekly single-needle arthrocenteses plus low Accepted for publication 13 September 2011 molecular weight HA (F). At the 3-month follow-up, (3, 4). Then, with the increase in knowledge on the roleof joint lubrication impairment as a risk factor for Literature data suggested that arthrocentesis may be of some benefit to manage symptoms of temporomandib- with sodium hyaluronate, viz., hyaluronic acid (HA), ular joint (TMJ) disorders, even though findings are not became an option for the management of symptoms in conclusive as for the potential additional effectiveness the clinical setting (5). This led to the progressive achieved with drugs injected immediately following expansion of potential clinical indications for the use of arthrocentesis plus HA injections, with particular regard The first works on TMJ arthrocentesis focused on its to joints with inflammatory-degenerative disorders (6, application to increase jaw function and achieve relief 7). Protocols for symptoms management in larger joints from pain in patients with restricted mouth opening provided the adoption of a cycle of 5 weekly HAinjections immediately following arthrocentesis (8, 9),and encouraging findings emerged also from long-term *This paper was based on data presented at the EACD congress inNaples, 23–26th September 2010.
case series on patients with TMJ disorders (10, 11).
Positive outcomes have also been described after TMJ patients of protocols C, E and F received 1 mL low injections with corticosteroid (12) and also with molecular weight HA†, and the patients of protocol D arthrocentesis alone (13), thus suggesting that defini- received 1 mL high molecular weight hylauronic acid‡.
tive information on the most suitable protocol as For protocols providing the injection of a drug after concerns the number of injections, the ideal HA arthrocentesis, one needle was removed after joint molecular weight and, more in general, on the most lavage, and the remaining one was used to inject the effective approach, viz., arthrocentesis alone or com- drug into the joint space. The single-needle technique, first introduced by Guarda-Nardini et al. (16), adopted In view of these considerations, in line with the need only one needle for both fluid injection and aspiration.
to perform exploratory trials on the issue, the aim of the Randomisation of patients between groups was present investigation was to compare the effectiveness achieved according to a [A-B-C-D-E-F-F-E-D-C-B-A] of six treatment protocols providing TMJ arthrocentesis sequence for inclusion in the different groups. For each with or without additional drugs to manage symptoms patient, a number of outcome parameters, viz., maxi- in patients with inflammatory-degenerative TMJ dis- mum pain at rest and maximum pain at chewing on a 10-point VAS scale with 0 being absence of pain and 10being the worst pain ever, subjective chewing efficiency(0–10 VAS scale with 0 being the worst efficiency ever and 10 the best efficiency ever), treatment tolerability A consecutive series of 72 patients with a Research and perceived treatment effectiveness on a 5-point Diagnostic Criteria for Temporomandibular Disorders Likert-type scale with 0 being the lowest and 4 the (RDC ⁄ TMD) version 1.0 (14) diagnosis of osteoarthritis maximum values, jaw range of motion function in (axis I group IIIb) with joint pain lasting from more millimetres, were assessed at baseline, at the end of than 6 months seeking for treatment at the TMD Clinic, treatment and at a 3-month follow-up. All interven- Department of Maxillofacial Surgery, University of tions were conducted by one of the two main inves- Padova, Italy, were randomly assigned to one of the groups receiving the following treatment protocols: above-described random sequence of intervention, single-session two-needle arthrocentesis (A), single- and the outcome parameters were recorded by the session two-needle arthrocentesis plus corticosteroid same trained dental student (D.R.) blinded to the (B), single-session two-needle arthrocentesis plus low treatment protocol for all patients. As far as practically molecular weight HA (C), single-session two-needle possible, patients were blinded to the treatment modal- arthrocentesis plus high molecular weight HA (D), ity; that is, a generic explanation of the potential benefit 5 weekly two-needle arthrocenteses plus low molecular of administering arthrocentesis was provided as well as weight HA (E) and 5 weekly single-needle arthrocent- an explanation that the specific intervention they were eses plus low molecular weight HA (F). Patients were undergoing was indicated for their disease. All patients instructed to have a 2-week wash-out period before gave their written consent after being informed on the starting the treatment protocol and to not use medica- tions on routine basis during the active treatment and Power analysis based on literature data (11) and assuming a mean VAS value of 6 ⁄ 10 Æ 3 ⁄ 10 in the The two-needle techniques refer to the approach first main outcome variable, viz., pain at chewing, revealed described by Nitzan et al. (3), with a needle dedicated to that the study design was able to detect a 57Æ1% the inflow of physiological saline into the upper joint between-group difference in mean pain at chewing compartment and a second needle for the outflow. The VAS values with a statistical power of 5% for type I error, joint lavage was performed with at least 300 mL of viz., false-positive results, and 20% for type II error, viz., saline (15). After joint lavage, patients of protocol B false-negative results. VAS pain levels and jaw range of received additional 1-mL triamcinolone injection*, motion values were managed as continuous variables,while data on subjective efficacy and tolerability levels †HyalganÒ, Fidia, Abano Terme, Italy.
*KenacortÒ, Bristol-Myers Squibb, Roma, Italy.
‡SynviscÒ, Genzyme s.r.l., Modena, Italy.
C O M P A R I S O N O F S I X T R E A T M E N T P R O T O C O L S were managed as ordinal variables. The existence of of unpleasant side effects, viz., joint swelling and strong differences between groups as for percentage changes post-injection increase in pain, in two of five subjects.
over time in all the outcome variables was assessed by So, the outcomes for such protocol were not described.
means of analysis of variance (ANOVA) for continuous No side effects were observed in any patients belonging variables and Kruskal–Wallis’ test for ordinal variables.
to the other treatment groups. Five patients dropped The percentage of patients of each group reporting an out from the study owing to different reasons, mainly improvement was compared by Fisher’s exact test. Also, because of work related or other difficulties to attend ANOVA and Fisher’s exact test were performed to inves- tigate, respectively, for differences in the mean age and to The number of patients completing treatment proto- compare sex distribution between groups. For all com- cols A, B, C, E and F, ranged from 9 to 12 (protocol A: parisons, statistical significance for between group dif- 11 patients; B: 9; C: 11; E: 12; F: 12), and no differences (P = 0Æ346) and sex distribution (P = 0Æ333). Baselinevalues of the five treatment groups were not signifi- cantly different in any of the outcome variables A total of 60 patients (mean age, 50Æ1 years; 51 women, (P-values ranging from 0Æ471 to 0Æ702) (Table 1). At nine men) completed the study. The treatment protocol the 3-month follow-up, improvement with respect to D (arthrocentesis plus high molecular weight HA) was mean baseline values was recorded in all the five interrupted after five patients owing to the occurrence treatment groups completing the protocol.
No significant differences emerged between groups in Table 1. Baseline values for the main outcome parameters.
any outcome variable (P-values ranging from 0Æ056 to Comparison between the treatment groups (one-way ANOVA) 0Æ989) (Table 2). Despite being not significant with respect to improvement achieved with other treat- ments, the protocol providing five sessions of two-needle arthrocenteses plus low molecular weight HA (protocol E) allowed achieving the highest improve- ment in almost all the outcome variables, among which maximum pain at chewing (64Æ9% decrease in VAS pain levels versus 11Æ5–41Æ3%; F = 1Æ727; P = 0Æ096).
Protocol E was also the most tolerable by the patients tnA, single-session two-needle arthrocentesis (protocol A); (2Æ5 versus 2Æ1–2Æ2 on a four-point Likert-type ordinal tnA + C, single-session two-needle arthrocentesis + corticoster- scale; F = 0Æ299; P = 0Æ877), while protocol B, viz., oids (protocol B); tnA + lwHA, single-session two-needle arthro- arthrocentesis plus corticosteroids injection, endorsed centesis + low-weight hyaluronic acid (protocol C); 5tnA + lwHA, the higher scores in subjectively perceived efficacy (3Æ0 5 weekly two-needle arthrocentesis + low-weight hyaluronic acid (protocol E), 5snA + lwHA, 5 weekly single-needle arthrocente- versus 2Æ1–2Æ6; F = 0Æ753; P = 0Æ561) (Table 3). Differ- sis + low-weight hyaluronic acid (protocol F).
ences between groups in the percentage of patients Table 2. Percentage changes at the end of the follow-up period with respect to baseline values. Comparison between the treatmentgroups (one-way ANOVA). In parentheses, the expected sign for improvement Table 3. Subjective efficacy and tolerability of the treatment on a treatment protocol to achieve pain relief and restore jaw 0–4 Likert scale. Comparison between the treatment groups function. Early papers suggested that the long-term benefit of corticosteroid injections in patients with TMJpain was equally effective than occlusal splints on subjective symptoms and allowed achieving a better improvement in clinical signs (17); also, their short-term effects were similar to HA injections (18). Later on, very few clinical trials have been performed to compare treatment effects of different joint lavage and injections protocol. In one study, the effects of a cycle of five HA injections immediately following arthrocentesis weresimilar to those of occlusal splints and superior to no treatment at 6 months (7); in a couple of investigationsperformed on the same study sample, no significantly Table 4. Percentage of subjects within each treatment groupreferring an improvement in their outcome parameters at the end different treatment effects at 6 months were detected of the follow-up. Comparison between the treatment groups between two HA and corticosteroid injections performed 2 weeks apart (12, 19); in another trial, a single HAinjection proved to be superior to oral anti-inflammatory drugs over a 3-month follow-up (20). In view of the paucity of investigations conducted on the issue, the two most recent systematic reviews of the literature, one dealing with the effectiveness of arthrocentesis (1) and the other one of HA (2), concluded that more research is needed to define better the indications and the risk-to- benefit ratio of the different injections protocol.
Considering the absence of a standard of reference technique for administering arthrocentesis, exploratory reporting an improvement in the outcome variables research is needed to gather data on the argument. The were not significant (P-values ranging from 0Æ263 to lack of a reference treatment made difficult to adhere 0Æ862) (Table 4). The highest percentage of improvers strictly to the criteria for conducting randomised and in pain variables was shown in patients belonging to controlled trials (CONSORT statement) (21). The pres- groups E (91Æ6%), F (66Æ6%) and C (63Æ6%), while ent investigation was the first to compare all the main groups receiving arthrocentesis alone (A) or with available options for washing and injecting the TMJ, corticosteroids (B) had about a 50% percentage of ranging from the single-session two-needle arthrocen- patients who improved with respect to baseline pain tesis technique described by Nitzan et al. (3) to the values. Protocol E also had the highest percentage of extensive protocol of 5 weekly HA injections immedi- patients referring an improvement in chewing effi- ately following arthrocentesis adopted by Guarda-Nar- ciency (66Æ7%). Treatment protocol B included the highest percentage of subjects improving in mouth injections after arthrocentesis (22) as well as a single- needle technique for arthrocentesis (16). Findings didnot support the clear superiority of one treatmentprotocol over the others to achieve pain management in TMJ inflammatory-degenerative joint disease over a The present investigation was specifically designed in short-term, viz., 3-month follow-up period. All proto- the attempt to get deeper into the knowledge on the cols were associated with positive outcomes, in line effectiveness of arthrocentesis and injections in the with the TMD literature suggesting that improvement management of inflammatory-degenerative disorders is, at least to some extent, partly because of unspecific of the TMJ. The available literature has been not treatment effects and to regression to the mean conclusive so far to indicate which is the most suitable C O M P A R I S O N O F S I X T R E A T M E N T P R O T O C O L S Notwithstanding that, some suggestions can be significant difference owing to the low statistical power, drawn on the potential inter-protocol effect differences.
should be diminished by the inclusion of larger First, the protocol providing high molecular weight HA samples. In any case, an appropriate a priori sample injections after arthrocentesis was withdrawn after two size analysis must be based on the selection of the post- subjects experienced joint swelling and post-injection treatment changes that are expected to be clinically pain increase. This may suggest that such HA prepara- relevant, and this is a very complex issue to deal with in tion is too viscous and has a too large steric interaction pain studies. Indeed, considering the clinical and that prevents from achieving a quick diffusion within logistic difficulties to perform large sample clinical trials the small TMJ intra-articular space. The rationale for on this issue, studies attempting to identify the clini- the adoption of high-viscosity HA stood in its potential cally significant VAS change threshold in patients with longer-lasting effects with respect to low molecular chronic TMJ pain have to be designed in the near weight preparations, but the present investigation did future as a compelling requisite to avoid type II errors in not provide encouraging findings on its potential the field of research on TMD treatment.
applications in TMJ disorders. Such finding has to be Third, protocol B, providing a single-session arthro- further investigated with future studies.
centesis plus corticosteroid injection, endorsed the Second, despite the absence of significant between- highest improvement in mouth opening values. Such group differences, a tendency towards a better improve- findings seem to be explainable with the lowest ment in patients included in protocol E, viz., 5 weekly baseline range of motion in that treatment group, even two-needle arthrocenteses plus low molecular weight if not clinically significant from the other groups.
HA injections, was detectable. Patients receiving such Patients included in protocol B also referred a higher treatment referred the most improvement in pain at subjective efficacy of the treatment, may be due to the chewing as well as chewing efficiency levels. In partic- positive effects perceived on mouth opening range and ular, the mean change in the pain at chewing scale was to the analgesic properties of corticosteroids.
5 ⁄ 10 on the VAS scale, accounting for more than a 64% Fourth, quite surprisingly, protocol E was tolerated improvement with respect to baseline values. All the better than the others, even if differences with the other protocols allowed an improvement of pain at other treatments were not significant. In any case, such chewing levels comprised between the 11% and 41% findings are interesting as far as concern the risk of range. Also, the protocol E group included the highest being an approach too much invasive and less tolerated percentage of improved patients as for pain at chewing by the patients. Also, the single-needle approach, that (91Æ7%), pain at rest (75%) and chewing efficiency was specifically introduced as a potentially better- levels (66Æ7%). The absence of statistically significant tolerated variance of the two-needle technique, pro- differences might be partly because of the statistical vided no positive outcomes in terms of patients’ power of the study, which was designed to detect between-group differences of more than 50% in the The above considerations may be open to several treatment-related improvement. Much larger sample interpretations, the most important of which being sizes might have been necessary to detect lower that, despite the 3-month follow-up did not evidence threshold differences: on the basis of data collected in significant differences between groups, studies on this investigation that may serve as a guide for power longer follow-up periods and enlarged sample sizes analysis of future studies, up to 24, 43, and 97 patients are needed to confirm findings. The short-term follow- per group needed to detect a 40%, 30%, and 20% up period of this investigation is indeed a limit to difference, respectively. The low sample size may generalisation of findings, and longer periods of post- explain also the tendency towards significance for treatment observation may help confirming or refuting differences in mouth opening values, as baseline values the tendencies described in this investigation. Also, in of patients included in the various treatment protocols the light of the absence of statistical significance for were not equal, even if not significantly different. Thus, apparently large between-group differences as those an enlargement of sample in future studies would allow detected for the percentage of improved subjects and reducing ⁄ avoiding potential shortcomings owing to the post-treatment changes in pain at chewing levels, unequal patients’ allocation within the treatment researches assessing the clinically significant VAS groups. Also, the risk for type II error, viz., missing a changes in chronic TMJ pain have to be performed, because the risk for type II errors appears to be too high of these findings need to be confirmed with future studies on larger samples with longer follow-up periods.
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