Effectiveness of Ozone Injection Therapy in

Temporomandibular Disorders
Sheila Haghighat and Samira Oshaghi
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Abstract

Temporomandibular disorder is a multifactorial disease that causes pain

in the jaw and face area with nondental origin, which frequently limits
talking, chewing, and other jaw activities. Various factors such as
malocclusion, trauma, stress, parafunctional habits (clenching and
bruxing), osteoarthritis, and synovitis play a role in its occurrence,
although the etiology of these disorders is little understood. Several
treatments are being used to treat these disorders. Ozone therapy has
been recently introduced as one of these treatments. Considering that no
extensive study has been found in this field so far, this study is aiming to
report the studies that have been conducted to determine the efficacy of
ozone injection therapy in temporomandibular joint disorders. This
report addresses the studies which are conducted clinically,
experimentally, and semi-experimentally over the past 10 years (2009–
2019). The prepared articles are screened according to the inclusion
criteria. In this study, total six related articles are addressed. One study
was pre- and postintervention, and five studies were clinical trials.
Studies show that although more studies are needed in contrast with
occlusal splint, ozone therapy is generally more effective treatment for
pain reduction compared to medication.

Keywords: Ozone therapy, jaw, temporomandibular joint disorders

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Introduction

The temporomandibular joint is a bilateral synovial joint formed by the

mandibular condyle and mandibular cavity of the temporal bone, and the
articular disc allows joint movements between them.[1] It is the most
active joint in the body and needs to be opened and closed
approximately 2000 times a day during chewing, speaking, breathing,
swallowing, and yawning.[2]

In this joint, the articular surfaces are not composed of hyaline cartilage
unlike most synovial joints of the body that are covered by the fibrous
tissue. This joint is the only joint system that has a definite and hard
closing end point that is the calcification occlusal surfaces of the teeth.[3]
Since the right and left condyles are parts of a movable mandibular, the
temporomandibular joint on the one side cannot have a function without
the movement of the joint on the other side.[4]

Temporomandibular disorder (TMD) is a multifactorial disease that

causes pain in the jaw and face area with nondental origin. These
disorders include muscle disorders, disc and condyle disorders, and
inflammatory joint disorders. Any factor that can change the normal
function of the masticatory muscles or their sensory input, joint fluid,
ligaments, disc and condyle tissues, and disrupt the normal balance of
the participating tissues in the temporomandibular joint, is considered
as an etiological factor of joint disorders.[5]

Etiological factors in occurring this disorder include acquired factors

such as infection, injury, iatrogenic (surgery, radiotherapy, habits,
tumors, and finally, idiopathic), hereditary factors such as hemifacial
microsomia, hemifacial atrophy, rheumatoid arthritis in young people
and onycholysis, and other factors such as muscle spasms, inappropriate
occlusal contact, stress, systemic diseases, and immunological factors.[6]

Tissue changes and psychological factors are the main predisposing

factors in occurring TMDs. It is often associated with degenerative
changes in its skeletal structures, such as flattening, erosion,
osteophytes, subchondral sclerosis, and false cysts.[7]

These bone changes may be without symptom in the early stages but in
the later advanced stages may be followed by clinical signs and
symptoms such as pain and dysfunction.[8] Radiographic examining is
part of the routine clinical evaluations of TMDs, and its main purpose is
to confirm bone degenerative changes in joint components and to
diagnose the disc displacement.[9]

The literature of the subject is rather rich. Some of the reports have
addressed the epidemiology of the disorder.[10,11] Some others have
indicated the symptoms that have to be observed in the diagnosis of the
disorder.[12,13,14]

Today, various morphological parameters of TMDs can be more fully and

accurately measured by the development of new techniques such as
computer tomography and cone-beam computer tomography. The
possibility of more complete analysis has been provided by the invention
of three-dimensional technologies, especially cone-beam computer
tomography.[15]

There are different ways to manage temporomandibular dysfunction.

The mainstay of the therapy is the combination of the drug treatment
with tricyclic antidepressant, physical modalities such as oral orthotic
devices, physical therapy, and intra-articular injection of the joint with
small amounts of local anesthetic and steroid.

After several years of research and development about a very innovative

treatment method called ozone therapy, the medical community has
recently concluded that it has many capabilities that can treat a variety
of joint and bone problems.[16]

Ozone is a colorless gas that each of its molecules is made up of three

oxygen atoms. These atoms are connected in a completely unstable way.
This substance will have an oxidizing effect on organic compounds due
to the positive charge in ozone. This ability is beneficial to neutralize
foreign cells that have a negative charge such as bacteria, yeasts, viruses,
and parasites, and it removes the active infections.[17]

The ozone which is used in medical science is made from pure oxygen
with ozone generator, and it is prescribed in the precise treatment doses.
The effect of ozone therapy on the body over the past few years has been
proven by various scientific studies, which is highly compatible with the
body, and it has the least side effects.[17]

In ozone therapy, ozone is converted into normal oxygen (O2) within 8

minutes after entering the body. During this conversion, some energy
and gamma-rays are produced which accelerate the healing process of
the damaged cells.

The authors couldn't find any coherent review in the literature about the
effectiveness of ozone therapy in the treatment of TMDs. Considering
that this disorder is observed in a relatively high percentage in all ages
and according to the increasing trend and promising results of using this
treatment method, this study is conducted to determine the treatment
effectiveness of ozone injection therapy in TMDs in the form of reviewing
articles to provide an accurate report of this treatment method, its
application, and effectiveness.
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Materials and Methods

Literature review was conducted in the Cochrane Library, MEEDLINE,

and EMBASE databases on the articles published over the past 10 years
(2010–2019). The search method was based on the following keywords:
ozone therapy, TMD, and musculoskeletal disorder. Abstracts of articles
were extracted using the selected keywords. After deleting completely
irrelevant articles, and some irrelevant articles were excluded again, the
full text of other related articles was prepared. Then, the text of all the
articles was examined and investigated according to the predetermined
inclusion criteria. Inclusion criteria were as follows: the relevance,
English language, comprehensive description of the figures and tables,
validity and reliability of the used method, place of research, adequacy of
the sample size, appropriate comparing of the findings with other
studies, and availability of the suggestions for future study. Exclusion
criterion was the inappropriate design of the survey method.
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Results

Six articles have investigated the ozone therapy of TMD out of the whole
descriptive and intervention published articles about ozone therapy and
TMDs over 10 years (2010–2019). One study was pre- and
postintervention, and five studies were clinical trials.

Doğ an et al.[18] studied 63 patients with TMDs in a clinical trial study.

Thirty-three patients were treated with oxidative ozone and 30 patients
were treated with thioglycoside capsules of ketoprofen tablets for 7
days. Patients assessed their pain using a Visual Analog Scale. The
average opening of the mouth in the group under treatment with ozone
in the preexperimental period was 46.51 ± 8.2 mm, and after 1 week of
the ozone therapy, this value immediately increased into 48.78 ± 7.5 mm
which was statistically significant (P = 0.04). For those who received the
drug, the average was 46.30 mm before treatment and 46.9 mm at the
end of 1 week. Overall, the results of the treatment were promising.[18]

In a clinical trial study, Celakil et al.[19] in 2019 examined 40 patients

who were randomly categorized into two groups of 20 patients (the
group of ozone therapy) and 20 patients (the group of occlusal splint).
The first group was treated with ozone three times a week for totally 6
sessions. Patients with occlusal splint were asked to use obstruction
splints every night for a period of 4 weeks. The results showed that
occlusal splint treatment was still a gold treatment method for pain relief
in patients with TMDs.[19]
Ö zalp et al.[20] in 2019 in an intervention study treated 40 patients with
TMD with ozone therapy with high frequency of ozone. Patients were
treated bilaterally three times a week with an ozone generator with high
frequency of ozone with intensity of 80% for 10 min. The pain scores and
maximal values of intermediate opening were assessed before and after
the intervention. The increase of average intermediate opening was
achieved after ozone therapy, although the difference was not
statistically significant. However, the average pain score decrease in the
patients treated with ozone therapy was statistically significant.[20]

In a clinical trial study, Reyes and Alghannam [21] in 2016 treated 57

patients with ozone. The volume of 3 ml, equivalent to 0.03 mg in a two-
way section, was used ten times. The pain decreased before the fourth
use of ozone (100%). Limitation of opening of the mouth was observed
in (100%) less than the deviation and deviation of the mandible.[21]

In a clinical trial study, Daif [22] in 2012 studied 60 patients (49 women
and 11 men) with TMD. They were randomly divided into two equal
groups. The first group was treated with direct injection of ozone gas
into the joint space. Each joint received 2 ml of a mixture of ozone and
oxygen (the concentration of ozone gas was 10μg/ml). Injections were
repeated two times a week for 3 weeks. The second group received
nonsteroidal anti-inflammatory drugs and muscle relaxants. Clinical
signs and symptoms before and after treatment were assessed based on
the clinical dysfunction index. The results showed that 87% of patients
who received injection of ozone gas into the superior joint space (26
patients) were completely recovered.[22]

In another clinical study, Hammuda et al.[23] employed ozone in

temporomandibular joint arthrocentesis. In their study, 30 patients were
divided into two groups. The first group subjected to arthrocentesis
using saline solution, while in the second group, arthrocentesis was
carried out using ozonized water. They concluded that although a
significant decrease in the pain level was observed in both the groups, a
significant decrease in the second group was reported at postoperative,
after the 1st month and 1 year. Furthermore, maximal mouth opening for
all patients in both the groups was improved, and the significant increase
was reported in Group II after the 1st month, 6 months, and 1 year
postoperatively.[23]

A summary of the results obtained in the six presented studies is shown

in Table 1.

Table 1
Ozone injection therapy in temporomandibular disorders

Sample Study
Final findings Title Year Author
size method
Injecting intra-
articular ozone gas is
a promising
treatment method for
managing the
Role of intra-
internal contraction
articular ozone gas
of the
injection in the
temporomandibular
60 management of
joint. However, Clinical trials 2012 Daif[22]
patients internal
more clinical and
derangement of the
experimental studies
temporomandibular
are needed to
joint
provide direct
evidence for
mechanism of its
performance and to
prove the results
29% of patients in
the ozone therapy
group and 24% of Effects of high-
patients in the drug frequency bio-
group experienced a 63 oxidative ozone Doğan et al.
Clinical trials 2014
gradual decrease in patients therapy in [18]
pain which the temporomandibular
difference between disorder-related pain
the two groups was
significant
Patients of the ozone 57 Clinical trials Ozone therapy as an 2016 Reyes and
therapy group patients alternative treatment Alghannam[21]
showed a significant to the pain in the
 Sample Study
Final findings Title Year Author
size method
decrease in the pain
temporomandibular
score compared to
disorder
the control group
Clinical efficacy of
arthrocentesis with
ozone in the
temporomandibular
joint internal
Use of Ozone in
derangements.
30 Temporomandibular Hammuda et
Efficacy of ozonized Clinical trial 2013
patients Joint Arthrocentesis, al.[23]
water as a clinically
Clinical Study
applicable form of
ozone in ozone
therapy for the
temporomandibular
joint
Movements of
mandible had a
significant
difference for the
time factor in both
ozone therapy and
occlusal splint
groups. Muscle pain
and pressure Management of pain
threshold was in TMD patients:
40 Celakil et al.
significantly higher Clinical trials Bio-oxidative ozone 2019
patients [19]
in the occlusal splint therapy versus
group. Both occlusal splints
treatments
statistically reduced
Visual Analog Scale
scores. However,
statistically, there
was no significant
difference between
the groups
The use of high- 40 Interventional Evaluation of the 2019 Özalp et al.[20]
frequency ozone patients Short-Term Efficacy
therapy can be a of Transdermal
good alternative for Ozone Therapy in
managing pain and Turkish Patients
jaw movements in with Internal
 Sample Study
Final findings Title Year Author
size method
patients with Derangement of the
temporomandibular Temporomandibular
disorder Joint
Open in a separate window

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Discussion

TMD is used to express all disorders related to the function of the

masticatory system, and its etiology is multifactorial. Treatments such as
cognitive behavioral therapy, physiotherapy (stimulation of the electrical
nerve through the skin), and medication are considered to manage the
first line of the disorder. Splint treatment is effective except the
treatment methods that reduce pain and improve the range of motion of
the mandible.[24,25]

One of the new treatments introduced is ozone therapy, about which no

extensive study has been conducted so far. The use of ozone gas as a
treatment method caused doubts due to its unstable molecular structure.
However, extensive research has shown that ozone dynamic resonance
structures have made some physiological interactions, which is
beneficial in treatment.[26]

The dosage of the ozone in the presented articles is outlined in Table 2.

Table 2
The dosage of the ozone for ozone therapy of the temporomandibular joint in different
studies

n Dosage Treatment period Explanation

18 30% concentration 3 times per week for 10 min
3 treatment sessions per week
19 10-100 μg/ml, 60% ozone intensity for 10 min, for 2 weeks; total 6
sessions
n Dosage Treatment period Explanation
10 min bilaterally, three times
20 80% ozone intensity
for a week
10 sections 3 mg/L for a volume of 3
21 ml equivalent to 0.03 mg in one 10 sessions Totally 3 mg
bilateral section
2 mL ozone-oxygen mixture (ozone gas Totally 120
22 2 times per week for 3 weeks
concentration 10 µg/mL) µg
Totally 14
23 70 μg /ml 200 ml totally
mg
Open in a separate window

As it is observed in Table 2, different researchers have treated TMD with

different dosages of the ozone. Since the method is new, there is no
standard protocol for the dosage of ozone. In general, it can be concluded
that ozone therapy with even low dosages of ozone can effectively
reduce the pain in TMD patients.

In six studies, one study was pre- and postintervention and five studies
were clinical trials.

An intervention study to measure the pain in patients before and after

ozone therapy showed that after ozone therapy, not only the patients'
pain decreases, but also the jaw range of movements in the patients
increased.

Among the four clinical trials, two studies explicitly stated that the group
under the ozone therapy was associated with a more pain reduction
compared to the group under drug treatment. One study evaluated the
results of ozone therapy positively but concluded that its extensive use
depended on further studies. Another study compared ozone therapy
and occlusal splint and found that both methods reduced pain in
patients, but there was no significant difference between the two groups
and ultimately evaluated that the occlusal splint treatment is more
effective.
The results of some other studies have shown that ozone improves the
joint faster than the traditional treatment. It could be due to the fact that
ozone is a highly reactive molecule, and as a result, it has the ability to
repair as well as reduce inflammation. It also produces cartilage while
being injected into the joint capsule.[27,28,29]
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Conclusion

Overall results show that ozone therapy is an effective way to treat pain
caused by TMD, and it is safe and effective than drug therapy. However,
more extensive studies are necessary on different communities at
different ages.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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