Comparison of 2 Hyaluronic Acid Drugs for the Treatment of

0

h

J Oral Maxillofac Surgxx:xxx, 2012

Comparison of 2 Hyaluronic Acid Drugsfor the Treatment of Temporomandibular

Joint OsteoarthritisLuca Guarda-Nardini, MD, DDS,* Cristina Cadorin, MD,†

Antonio Frizziero, MD,‡ Giuseppe Ferronato, MD, DDS,§ and

Daniele Manfredini, DDS, PhD�

Purpose: To compare the effectiveness of 2 treatment protocols providing 5 weekly temporomandib-ular joint (TMJ) arthrocenteses immediately followed by injections of 2 different molecular weighthyaluronic acid (HA) drugs to manage symptoms in patients with inflammatory-degenerative TMJ disease.

Materials and Methods: Patients with a Research Diagnostic Criteria for Temporomandibular Disor-ders diagnosis of osteoarthritis were randomly assigned to 1 of 2 study groups receiving either low– ormedium–molecular weight HA after arthrocentesis. The level of maximum pain at chewing was theprimary outcome variable, and maximum pain at rest, subjective chewing efficiency, functional limita-tion, treatment tolerability, perceived treatment effectiveness, and jaw range-of-motion function inmillimeters were the secondary outcomes. All variables were assessed and compared between groups atbaseline, at the end of treatment, and 3 months later.

Results: Forty subjects entered the study. At the end of the follow-up period, all the outcome variablesimproved in both groups of patients. A between-group comparison of changes over time showed thatdifferences were not significant for any of the outcome variables, that is, pain at chewing (F � 0.056,P � .815), pain at rest (F � 0.383, P � .541), chewing efficiency (F � 0.050, P � .825), functionallimitation (F � 0.268, P � .609), and mouth opening (F � 0.003, P � .954). In addition, no between-group differences were shown for perceived treatment effectiveness and treatment tolerability.

Conclusions: Similar positive effectiveness was shown for 2 treatment protocols for TMJ osteoarthritis(ie, 5-session single-needle arthrocentesis plus low– or medium–molecular weight HA).© 2012 American Association of Oral and Maxillofacial Surgeons
J Oral Maxillofac Surg xx:xxx, 2012
ctmiw

The first works on temporomandibular joint (TMJ)arthrocentesis focused on its application to increasejaw function and achieve relief from pain in patientswith restricted mouth opening.1,2 Then, with the in-crease of knowledge on the role of joint lubricationimpairment as a risk factor for TMJ internal derange-ments, viscosupplementation with sodium hyaluro-nate, that is, hyaluronic acid (HA), became an option

Received from the University of Padova, Padua, Italy.

*TMD Clinic, Department of Maxillofacial Surgery.

†School of Rehabilitation Medicine.

‡School of Rehabilitation Medicine.

§TMD Clinic, Department of Maxillofacial Surgery.

�TMD Clinic, Department of Maxillofacial Surgery.

Address correspondence and reprint requests to Dr Manfredini:

Viale XX Settembre 298, 54033 Marina di Carrara (MS), Italy; e-mail:

[email protected]

© 2012 American Association of Oral and Maxillofacial Surgeons

278-2391/12/xx0x-0$36.00/0

ttp://dx.doi.org/10.1016/j.joms.2012.07.020

1

for the management of symptoms in the clinical set-ting.3 This led to the progressive expansion of poten-tial clinical indications for the use of arthrocentesisplus HA injections, with particular regard to jointswith inflammatory-degenerative disorders.4,5 Proto-ols for symptom management in larger joints providedhe adoption of a cycle of 5 weekly HA injections im-ediately after arthrocentesis,6,7 and encouraging find-

ngs also emerged from long-term case series on patientsith TMJ disorders,8,9 as well as from a previous clinical

trial from our research group supporting the superi-ority of multiple-injection protocols with respect tosingle-session joint lavage.10

Notwithstanding the previously mentioned find-ings, definitive information on the most suitable pro-tocol as concerns the number of injections, the idealHA molecular weight, and—more in general—themost effective approach (ie, arthrocentesis alone orcombined with drugs) is still to be gathered.11 Amongthese aspects, comparative trials on the effectiveness
of HA drugs of different molecular weight may be
mailto:[email protected]

http://dx.doi.org/10.1016/j.joms.2012.07.020

Oral M

2 HYALURONIC ACID AND TMJ OSTEOARTHRITISAQ: 1

useful to add information to the existing amount ofknowledge on TMJ injections.

In view of these considerations and in line with theneed to perform exploratory trials on the issue, theaim of this investigation was to answer the followingquestion: In patients with TMJ osteoarthritis who un-derwent a treatment protocol of 5 weekly arthrocen-teses plus HA injection, does treatment effectivenessat 3 months depend on the use of different molecularweight HA? The null hypothesis was that there are nodifferences between the protocols using the differentmolecular weight HAs. To test the hypothesis, wecompared treatment-related changes in some clinicaloutcome variables between patients receiving low–molecular weight HA and patients receiving medium–molecular weight HA.

Materials and Methods

To address the research purpose, we designed anexploratory randomized clinical trial. The study pop-ulation was composed of consecutive patients with aResearch Diagnostic Criteria for TemporomandibularDisorders version 1.012 diagnosis of osteoarthritis(axis I group IIIb) with joint pain lasting for more than

FIGURE 1. Flow diagram of progre

Guarda-Nardini et al. Hyaluronic Acid and TMJ Osteoarthritis. J

Table 1. COMPARISON OF DEMOGRAPHIC FEATURES ASTUDY GROUPS

Study Variable G

Women (%)Mean age (yr)Pain at rest (0-10 on VAS)Pain at chewing (0-10 on VAS)Chewing efficiency (0-10 on VAS)Functional limitation (0-4 on Likert-type scale)Mouth opening (mm)

Guarda-Nardini et al. Hyaluronic Acid and TMJ Osteoarthritis. J Oral M

6 months seeking treatment at the TMD Clinic, De-partment of Maxillofacial Surgery, University of Pa-dova, Padua, Italy, who were randomly assigned to 1of 2 study groups. Both groups of patients underwent5 weekly single-needle arthrocenteses plus HA injec-tion and a 3-month follow-up period. According to analternate allocation of patients into the 2 groups,patients received 1 of 2 different types of HA, whichwas the same for all 5 sessions. Patients were in-structed to undergo a 2-week washout period beforestarting the treatment protocol and to not use medi-cations on a routine basis during the active treatmentand follow-up periods (ie, only 500 mg of acetamin-ophen was allowed in the immediate post-interven-tion phases).

The single-needle technique refers to the approachfirst described by Guarda-Nardini et al,13 which ad-opted only 1 needle for both saline fluid injection andejection. The technique was performed with the pa-tient under local anesthesia, and on average, about 10mL of saline fluid was used for joint lavage. After jointlavage, patients in group A received 1 mL of medium–molecular weight (ie, 1,200-kDa) HA (Sinovial; IBSAFarmaceutici, Lodi, Italy), and patients in group B

ugh different phases of clinical trial.

axillofac Surg 2012.

ASELINE VALUES IN OUTCOME VARIABLES BETWEEN

(n � 17) Group B (n � 18) P Value

82 88 .337� 15.0 52.9 � 16.1 .329� 2.2 2.5 � 3.1 .552� 2.5 5.1 � 2.7 .889� 1.6 6.4 � 1.3 .062� 1.0 1.8 � 0.9 .303� 8.4 36.7 � 5.7 .946

ss thro

ND B

roup A

47.71.95.27.41.6

36.9


G

GUARDA-NARDINI ET AL 3

received 1 mL of low–molecular weight (ie, 600-kDa)HA (Hyalgan; Fidia, Abano Terme, Italy).

To ascertain the needed sample size for the inves-tigation, the primary outcome variable was treatmenteffectiveness based on the assessment of pain levels atchewing on a 10-point visual analog scale (VAS), with0 being absence of pain and 10 being the worst painever. An a priori power analysis based on literaturedata9 and assuming a mean VAS value of 6 � 3 (out of10) for the main outcome variable, that is, pain at

FIGURE 2. Changes over time (x-axis) in pain-at-chewing VAS scofor both groups (P � .001). Between-group differences in change

Table 2. SIGNIFICANCE OF DIFFERENCES INTREATMENT EFFECTIVENESS WITH RESPECT TOGENDER AND AGE

Outcome Variable

P Value

Gender Age

Pain at rest (0-10 on VAS) .415 .617Pain at chewing (0-10 on VAS) .333 .842Chewing efficiency (0-10 on VAS) .412 .527Functional limitation (0-4 on

Likert-type scale) .659 .735Mouth opening (mm) .583 .612

Guarda-Nardini et al. Hyaluronic Acid and TMJ Osteoarthritis.J Oral Maxillofac Surg 2012.

uarda-Nardini et al. Hyaluronic Acid and TMJ Osteoarthritis. J Oral M

chewing, showed that a 40-subject study design wasneeded to detect about a 40% between-group differ-ence in mean VAS values for pain at chewing with astatistical power of 5% for type I error (ie, false-positive results) and 20% for type II error (ie, false-negative results).

For each patient, a number of secondary outcomeparameters were assessed: maximum pain at rest on a10-point VAS with the same extreme points as thepain-at-chewing scale; subjective chewing efficiency(0-10 VAS, with 0 being the worst efficiency ever and10 the best efficiency ever); functional limitation;treatment tolerability and perceived treatment effec-tiveness on a 5-point scale, with 0 being the lowestand 4 the maximum value; and jaw range-of-motionfunction in millimeters. All variables were evaluated atbaseline, at the end of treatment, and at a 3-monthfollow-up after the end of treatment. All interventionswere performed by 1 of the 2 main investigators(D.M. and L.G.-N.) in accordance with the previouslydescribed random sequence of intervention, and theoutcome parameters were recorded by the same cli-nician (C.C.) fully blinded to the type of HA injectedin the patients. In an attempt to achieve a double-blind design, we did not tell the patients which of the

xis) in the 2 study groups. Improvement over time was significantime were not significant (P � .815).

res (y-as over t


4 HYALURONIC ACID AND TMJ OSTEOARTHRITIS

2 HA solutions was injected into the joint; they re-ceived a generic explanation of the potential benefitof administering arthrocentesis plus HA injections, aswell as an explanation that the specific interventionthat they were undergoing was indicated for theirdisease. All patients gave their written consent afterbeing informed about the study’s aims and design.Official approval by the University Review Board andMedical Direction was received (authorization code50361).

For statistical purposes, VAS pain levels and jawrange-of-motion values were managed as continuousvariables, whereas data on subjective efficacy andtolerability levels were managed as ordinal variables.For all variables, analysis of variance for repeatedmeasures was performed to assess the existence ofsignificant within-group and between-group treat-ment effects. Adjustments for age and gender wereperformed to assess the influence of demographicfeatures on treatment effectiveness. For all compari-sons, statistical significance for differences was set atP � .05.

FIGURE 3. Changes over time (x-axis) in pain-at-rest VAS scoresgroup B (P � .002), whereas it was not significant for group Asignificant (P � .541).


Results

A total of 40 consecutive patients entered the studyprotocol. The treatment protocol and follow-up pe-riod were completed by 17 patients (82% of whomwere female patients; mean age, 47.7 � 15.0 years)assigned to protocol A and 18 patients (88% of whomwere female patients; mean age, 52.9 � 16.1 years)assigned to protocol B. Between-group gender (�2 �2.17, P � .337) and age (t � �0.990, P � .329)differences were not significant. The remaining 5 pa-tients (3 in group A and 2 in group B) did not com-plete the treatment protocol (1 subject) or strictlyfollow the weekly appointments (4 subjects) becauseof personal problems that prevented them from at-tending the clinic regularly (Fig 1). Baseline levels inthe outcome parameters were not different betweenthe 2 groups, with P values ranging from .062 to .946(Table 1).

At the end of the follow-up period, both groups ofpatients improved with regard to all the outcomevariables. The effect of treatment was not different

in the 2 study groups. Improvement over time was significant for242). Between-group differences in changes over time were not

(y-axis)(P � .


io

cw(nweaa

sic

0

P

(

G Oral M


with regard to age and gender, thus not being influ-enced by the demographic features of the sample(Table 2). Patients in group A reported significantmprovement in pain at chewing (P � .001), mouthpening (P � .003), chewing efficiency (P � .004),

and functional limitation (P � .041), whereas im-provement in pain at rest was not significant (P �.242). Patients in group B reported significant im-provement in chewing efficiency (P � .001), pain athewing (P � .001), and pain at rest (P � .002),hereas improvement over time in mouth opening

P � .106) and functional limitation (P � .211) wasot significant. No relevant adverse or side effectsere observed in any patients, with the only minor

xception of a transient anesthesia of the temporalnd zygomatic branches of the facial nerve area aftern intervention in 3 patients.

Between-group comparison of changes over timehowed that differences were not significant eithern the primary outcome variables, that is, pain athewing (F � 0.056, P � .815) (Fig 2), or in the

other outcome variables, that is, pain at rest (F �

FIGURE 4. Changes over time (x-axis) in VAS scores for chewinsignificant for both groups (group B, P � .001; group A, P � .00P � .825).

uarda-Nardini et al. Hyaluronic Acid and TMJ Osteoarthritis. J

.383, P � .541) (Fig 3), chewing efficiency (F �

0.050, P � .825) (Fig 4), functional limitation (F � 0.268,� .609) (Fig 5), and mouth opening (F �

0.003, P � .954) (Fig 6). In addition, no between-group differences were shown for perceived treat-ment effectiveness and treatment tolerability (Table3). The null hypothesis that there are no differencesbetween the protocols using the different molecularweight HAs could not be rejected.

Discussion

The available literature has not been conclusive sofar in terms of indicating which is the most suitableviscosupplementation protocol to achieve pain reliefand restore jaw function in patients with TMJ osteo-arthritis.11 So, there is a need to gather as much dataas possible to explore the effectiveness of the differ-ent protocols’ features (eg, number and sites of injec-tions, HA molecular weight, and combination witharthrocentesis) for the different conditions (eg, phys-ical and psychosocial diagnoses). Considering thesedrawbacks, as part of an ongoing attempt to gain

iency (y-axis) in the 2 study groups. Improvement over time wasween-group differences in changes over time were not significant


g effic4). Bet

deeper knowledge on the effectiveness of arthrocen-

ciwdtmwdrpw

tawgmpB

tptlsTgmaitd

o

G Oral M


tesis and injections in the management of inflam-matory-degenerative disorders of the TMJ, investiga-tions were performed by our research group toidentify predictors of treatment effectiveness14 and toompare different protocols.10,15 With these prem-ses, the aim of the present investigation was to assess

hether, in patients with TMJ osteoarthritis who un-erwent a treatment protocol of 5 weekly arthrocen-eses plus HA injection, treatment effectiveness at 3onths depends on the use of different moleculareight HA. To address the research question, weesigned a clinical trial to compare the treatment-elated changes in some clinical outcome variables inatients receiving low– versus medium–moleculareight HA.Findings suggested that both protocols were effec-

ive in improving symptoms at the 3-month follow-up,nd no between-protocol differences in effectivenessere shown. These findings are open to several sug-

estions with regard to the magnitude of the treat-ent effectiveness and to the comparison of the 2rotocols providing HA of different molecular weight.

FIGURE 5. Changes over time (x-axis) in 5-point Likert-type scorestime was significant for group A (P � .041), whereas it was not sver time were not significant (P � .609).


oth study groups improved significantly with regard

o most outcome variables, with a 57.8% reduction inain-at-chewing levels for group A and a 59.3% reduc-ion for group B. These findings are in line withiterature data supporting the effectiveness of 5-ses-ion single-needle arthrocentesis plus HA injection forMJ osteoarthritis. Importantly, the fact that between-roup differences were not significant suggests thatedium–molecular weight HA is equally as effective

s low–molecular weight HA. This finding assumesmportance in light of previous reports on the adop-ion of low–molecular weight HA in patients with TMJisorders16-18 and may be worthy of further explora-

tion with future trials.The adoption of the 5-injection protocol for visco-

supplementation of the TMJ was based on similarapproaches adopted for larger joints, and a recentrandomized controlled trial by our group suggestedthat it may be viewed as the most effective approachfor viscosupplementation of the TMJ.10 The samestudy also concluded that high–molecular weight HAis not suitable for injecting the TMJ because of its highviscosity and large steric interaction that prevents one

ctional limitation (y-axis) in the 2 study groups. Improvement overnt for group B (P � .211). Between-group differences in changes


for funignifica

from achieving a quick diffusion within the small

vrdtr

iacfrbptmwtt

s

G Oral M


TMJ intra-articular space. Notwithstanding that, noinformation is available on the effectiveness of usingHA of medium molecular weight, which is the ratio-nale underlying this investigation. Another compara-tive trial suggested that no differences existed in pro-tocols adopting the classical 2-needle technique orthe newly introduced single-needle technique for ad-ministering arthrocentesis.15 For that reason, our in-estigation adopted the single-needle technique toeduce the number of needles inserted into the jointuring the 5-session protocol, to avoid the outflow ofhe HA from the second skin hole and, possibly,educe the patient’s discomfort.

FIGURE 6. Changes over time (x-axis) in millimeters of mouth opefor group A (P � .003), whereas it was not significant for groupignificant (P � .954).


Table 3. BETWEEN-GROUP COMPARISON (t TEST) FORTOLERABILITY AT END OF FOLLOW-UP PERIOD

Outcome Variable Group A (

Perceived treatment effectiveness 2.6 �Treatment tolerability 3.0 �


Indeed, the risk for overtreating the TMJ, especiallyf one is performing the 2-needle arthrocentesis with

total of 10 needles inserted into the small jointavity within a 5-week span, cannot be denied. As aurther step on the way to reduce joint trauma, aeduction of the number of serial injections seems toe a promising strategy, and the use of HA withotentially longer-lasting activity is an option worthyo be explored to pursue that goal. The medium–olecular weight HA adopted in this investigationas shown to be equally as effective and tolerable as

he commonly used low–molecular weight prepara-ion, showing an absence of side effects that charac-

axis) in the 2 study groups. Improvement over time was significant.106). Between-group differences in changes over time were not


IVED TREATMENT EFFECTIVENESS AND TREATMENT

7) Group B (n � 18) P Value

2.5 � 0.8 .8792.4 � 0.9 .116

ning (y-B (P �

PERCE

n � 1

1.10.9


fiomibwtsaiesrio

bp


terized previous experimental use of higher–molecu-lar weight HA for TMJ disorders.10 In view of theseconsiderations, data gathered in this investigationmay be viewed as a starting point to explore thepossibility to identify less invasive protocols, with areduced number of serial injections by the use ofmedium–molecular weight HA.

Longer follow-up periods are strongly needed to sup-port these findings, even though it must be borne inmind that the technique used in our study as a compar-ison reference (ie, 5-session single-needle arthrocentesisplus low–molecular weight HA injections) was alreadyshown to be effective for longer post-treatment spansthan that adopted in this study.15

Generally, despite the need to define potentiallyless invasive protocols and to better identify, the in-dications for performing joint lavage and injections, itshould also be stressed that no side effects have beenreported with the adoption of the described protocol.The worst, and only, discomfort noted by the patient isthe unpleasant feeling associated with the transient ef-fects of the local anesthesia in the TMJ area, as shown bythe good tolerability level. So, safety in use for thetechnique described in this study has been supported,and future studies might help to define the neededlearning curve for approaching TMJ arthrocentesis andinjection with a good risk management strategy.

From a methodologic viewpoint, it should be bornein mind that, because of the paucity of available dataon these treatment protocols, it was difficult to ad-here strictly to the criteria for conducting randomizedcontrolled trials.19 In particular, along with compari-sons with placebo, injection techniques must withstandcomparison with other conservative approaches, suchas oral appliances, physiotherapy, and cognitive-behav-ioral treatments. With this premise, specific studydesigns for comparison with other treatments mustbe adopted on the basis of the CONSORT (Consoli-dated Standards of Reporting Trials) guidelines forreporting clinical trials,19 with additional strategiesor measuring pain in a multidimensional conceptual-zation and for controlling for symptoms’ fluctuationver time. Notwithstanding that, it should be kept inind that the peculiar nature of the treatments under

nvestigation prevents one from achieving a full dou-le-blind design, because the operators were blindith respect to the patients’ outcome parameters but

he operators could not obviously be blind with re-pect to the technique they were performing. Actu-lly, the expertise of the investigators performing thenterventions and the expertise of the blinded singlexaminer recording the patients’ outcome parameterseem to be key factors to warrant the validity of theesults and should be taken into account also in futurenvestigations. As a further suggestion for the design
f future studies, it can be pointed out that, on the
asis of data gathered in this study and in our previousublication,10 much larger sample sizes are necessary

to detect lower threshold differences; for instance, upto 43 patients per group and 97 patients per group areneeded to detect 30% and 20% between-group differ-ences, respectively. Thus, considering the clinical andlogistic difficulties in performing large-sample clinicaltrials on this issue, studies attempting to identify theclinically significant VAS change threshold in patientswith chronic TMJ pain have to be designed in the nearfuture to avoid type II errors in the field of researchon TMJ disorder treatment. Keeping this in mind, thedesign of multicenter studies has to be taken intoaccount as a possible strategy to increase the externalvalidity of these findings.

Within the limits of this investigation, similar posi-tive effectiveness was shown for 2 treatment proto-cols for TMJ osteoarthritis (ie, 5-session single-needlearthrocentesis plus low– or medium–molecular weightHA). The null hypothesis that no differences existedbetween the protocols using the different molecularweight HAs could not be rejected. Future investiga-tions with longer follow-up periods and possibly in-cluding other comparison protocols (eg, saline fluidinjections) have to be planned to increase knowledgeon the strategies to perform TMJ arthrocentesis andinjections in patients with TMJ inflammatory-degener-ative disorders.

Acknowledgments

The authors thank Dr Stefano Masiero, Head of the School ofRehabilitation Medicine, University of Padova, for his help in thecoordination of this investigation.

References1. Nitzan DW, Dolwick MF, Martinez GA: Temporomandibular

joint arthrocentesis: A simplified treatment for severe, limitedmouth opening. J Oral Maxillofac Surg 49:1163, 1991

2. Nitzan DW, Samson B, Better H: Long-term outcome of arthro-centesis for sudden-onset, persistent, severe closed lock of thetemporomandibular joint. J Oral Maxillofac Surg 55:151, 1997

3. Nitzan DW: “Friction and adhesive forces”—Possible underly-ing causes for temporomandibular joint internal derangement.Cells Tissues Organs 174:6, 2003

4. Guarda-Nardini L, Tito R, Staffieri A, et al: Treatment of patientswith arthrosis of the temporomandibular joint by infiltration ofsodium hyaluronate: A preliminary study. Eur Arch Otorhino-laryngol 259:279, 2002

5. Guarda-Nardini L, Masiero S, Marioni G: Conservative treatmentof temporomandibular joint osteoarthrosis: Intra-articular injec-tion of sodium hyaluronate. J Oral Rehabil 32:729, 2005

6. Axe MJ, Shields CL: Potential applications of hyaluronans inorthopaedics: Degenerative joint disease, surgical recovery,trauma and sports injuries. Sports Med 35:853, 2005

7. Ehrlich GE: Osteoarthritis, in Rakel BE, Bope ET (eds). Conn’sCurrent Therapy (ed 58). New York, NY, Elsevier, 2006, p 921

8. Guarda-Nardini L, Stifano M, Brombin C, et al: A one-year caseseries of arthrocentesis with hyaluronic acid injections fortemporomandibular joint osteoarthritis. Oral Surg Oral MedOral Pathol Oral Radiol Endod 103:14, 2007

9. Manfredini D, Bonnini S, Arboretti R, et al: Temporomandibular
joint osteoarthritis: An open label trial of 76 patients treated

1

1

1

1

1

1

1

1

1

1


with arthrocentesis plus hyaluronic acid injections. Int J OralMaxillofac Surg 38:827, 2009

0. Manfredini D, Rancitelli D, Ferronato G, et al: Arthrocentesiswith or without additional drugs in temporomandibular jointinflammatory-degenerative disease: Comparison of six treat-ment protocols. J Oral Rehabil 39:245, 2012

1. Manfredini D, Piccotti F, Guarda-Nardini L: Hyaluronic acid inthe treatment of TMJ disorders: A systematic review of theliterature. Cranio 28:166, 2010

2. Dworkin S, LeResche L: Research diagnostic criteria for tem-poromandibular disorders: Review, criteria examinations andspecifications, critique. J Craniomandib Disord 6:301, 1992

3. Guarda-Nardini L, Manfredini D, Ferronato G: Arthrocentesis ofthe temporomandibular joint: A proposal for a single-needletechnique. Oral Surg Oral Med Oral Pathol Oral Radiol Endod106:483, 2008

4. Guarda-Nardini L, Ferronato G, Favero L, et al: Predictive fac-tors of hyaluronic acid injections short-term effectiveness for
TMJ degenerative joint disease. J Oral Rehabil 38:315, 2011
5. Guarda-Nardini L, Ferronato F, Manfredini D: Two-needle vs.single-needle technique for TMJ arthrocentesis plus hyaluronicacid injections: A comparative trial over a six-month follow up.Int J Oral Maxillofac Surg 41:506, 2012

6. Kopp S, Wenneberg B, Haraldson T, et al: The short-term effectof intra-articular injections of sodium hyaluronate and cortico-steroid on temporomandibular joint pain and dysfunction.J Oral Maxillofac Surg 43:429, 1985

7. Møystad A, Mork-Knutsen BB, Bjørnland T: Injection of sodiumhyaluronate compared to a corticosteroid in the treatment ofpatients with temporomandibular joint osteoarthritis: A CTevaluation. Oral Surg Oral Med Oral Pathol Oral Radiol Endod105:e53, 2008

8. Alpaslan GH, Alpaslan C: Efficacy of temporomandibular jointarthrocentesis with and without injection of sodium hyaluro-nate in treatment of internal derangements. J Oral MaxillofacSurg 59:613, 2001

9. Altman DG, Schulz KF, Moher D, et al: The revised CONSORT
statement for reporting randomized trials: Explanation andelaboration. Ann Intern Med 134:663, 2001

Documents

Comparison of 2 Hyaluronic Acid Drugs for the Treatment of