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Clinical utility of ozone therapy for musculoskeletal disorders



Oxygen-ozone (O3) therapy serves as an alternative medical technique that increases the oxygen in the body along with the introduction of O3. O3 therapy has finally reached a level where the biological mechanisms of action have been understood, showing that they are in the domain of physiology, biochemistry, and pharmacology. Few clinical applications have been reviewed here as well as exemplifying that O3 therapy is particularly useful in musculoskeletal disorders. In the therapeutic range, O3 can be used as a more effective and safe substitute of standard medications. O3 therapy has been used for many years for its ability to inactivate various viruses, cancer, and acquired immune deficiency syndrome but is now making strides in the treatment of musculoskeletal disorders such as rheumatoid arthritis, lumbar facet joint syndrome, subacromial bursitis, carpal tunnel syndrome, osteoarthritis, hip bursitis, shoulder adhesive capsulitis, herniated disc, and temporomandibular joint disorder.
© 2018 Medical Gas Research | Published by Wolters Kluwer - Medknow 103
Ozone (O3) has great oxidizing activity as a soluble gas. When
in contact with biological uids, it forms reactive oxygen
species as well as lipid oxidation products.1 Both of these
products react with white blood cells initiating the formation
of proteins, cytokines, and red blood cells which increases the
tissue oxygen supply. O3 is used to treat many cases regarding
the muscles, tendons, and joints. O3 therapy raises the pain
thresholdas it works based on stimulating antinociceptive ap-
paratus mediated by serotonin and endogenous opioids. Due
to neoangiogenesis, O3 allows for vascularization caused from
tissue hyperoxygenation. Therefore, the inhibitory capacity of
inammatory metabolites is improved as well as local tissue
trophism. There is a common theme among many literature
reports that O3 reduces local pain which favors the mobility
lost during the painful state and recovery of joint function.2,3
O3 can be injected by peri-articular, intra-articular, or percu-
taneous means. It is considered a satisfactory treatment with
a low risk of complications and high success rate.
An endogenous cascade is started when beginning the use
of O3 therapy. In response, a stress is induced from the bio-
logically active substrates that are released. Because of O3’s
ability to dissolve in the aqueous component of plasma, it can
cause this oxidative stress.4 Hydrogen peroxide and a reac-
tive species (ROS) are formed when O3 reacts with water and
polyunsaturated fatty acids. When inhaled, the O3 reacts with
polyunsaturated fatty acids that are found in the alveolar lin-
ing layer. A mixture of lipid ozonation products (LOP) is also
formed simultaneously such as malonlydialdehyde, lipperoxyl-
radicals, hydroperoxides, isoprostanes, 4-hydroxynonenal, and
alkenals.5 The activation of the transcriptional factor mediating
nuclear factor-erythroid 2-related factor 2 (NRF2) is increases
with the moderate oxidative stress caused by O3. The role of
NRF2 is to activate the transcription of antioxidant response
elements. A variety of antioxidant enzymes attain an increased
concentration level upon introduction of antioxidant response
elements. Some of the antioxidants include glutathione S-
transferase (GST), catalase (CAT), heme oxygenase (HO)-1,
superoxide dismutase, glutathione peroxidase, heat shock
proteins and quinone-oxidoreductase. most of these enzymes
play a role as free radical scavengers in a range of diseases.5
Depending on the cell’s redox status and the amount given,
O3 and other medical gases such as nitric oxide and carbon
monoxide have a twofold effect. O3 overexpresses HO-1 or
heat shock proteins (HSPs) of 32 kPa which produces nitric
oxide.6 The expression levels of Hsp70 are upregulated by O3
which is related to HO-1. Therefore, there may be a develop-
ing role in therapy of free radical-based diseases. Heme is
enzymatically degraded by HO-1 and can be toxic depending
on free iron, amount produced, and bilverdin. Biliverdin is
a neutralizer of nitrosative and oxidative stress based on the
ability to interact with reactive nitrogen species and NO.7,8 It
was found recently that the heat shock response provided a
cytoprotective state during aging, cancer, neurodegenerative
disorders and inammation.9 Throughout the phylogenetic
spectrum, HO isoforms are found to be as regulators of redox
homeostasis and dynamic sensors of cellular oxidative stress.
Hormesis is a defense mechanism for oxidative insults to
Clinical utility of ozone therapy for musculoskeletal
Omar Seyam1, Noel L. Smith2, Inea Reid1, Jason Gandhi1, 3, Wendy Jiang1, Sardar Ali Khan1, 4, *
1 Department of Physiology and Biophysics, Stony Brook University School of Medicine, Stony Brook, NY, USA
2 Foley Plaza Medical, New York, NY, USA
3 Medical Student Research Institute, St. George’s University School of Medicine, Grenada, West Indies
4 Department of Urology, Stony Brook University School of Medicine, Stony Brook, NY, USA
*Correspondence to: Sardar Ali Khan, MD, FRCS, FACS,
orcid: 0000-0002-4759-530X (Sardar Ali Khan)
Oxygen-ozone (O3) therapy serves as an alternative medical technique that increases the oxygen in the body along with the introduction of
O3. O3 therapy has nally reached a level where the biological mechanisms of action have been understood, showing that they are in the
domain of physiology, biochemistry, and pharmacology. Few clinical applications have been reviewed here as well as exemplifying that O3
therapy is particularly useful in musculoskeletal disorders. In the therapeutic range, O3 can be used as a more effective and safe substitute
of standard medications. O3 therapy has been used for many years for its ability to inactivate various viruses, cancer, and acquired immune
deciency syndrome but is now making strides in the treatment of musculoskeletal disorders such as rheumatoid arthritis, lumbar facet
joint syndrome, subacromial bursitis, carpal tunnel syndrome, osteoarthritis, hip bursitis, shoulder adhesive capsulitis, herniated disc, and
temporomandibular joint disorder.
Key words: oxygen-ozone therapy; osteoarthritis; herniated disc; carpal tunnel syndrome; lumbar facet syndrome; muscle oxygenation,
bromyalgia; cervical disc herniation
doi: 10.4103/2045-9912.241075
How to cite this article: Seyam O, Smith NL, Reid I, Gandhi J, Jiang W, Khan SA. Clinical utility of ozone therapy for musculoskeletal
disorders. Med Gas Res. 2018;8(3):103-110.
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Seyam et al. / Med Gas Res
Medical Gas Research ¦ September ¦ Volume 8 ¦ Issue 3
multiple organ systems.9 O3 can have a role in hormesis by
regulating the proinammatory and anti-inammatory effects
of prostaglandin formation which is of similar nature to nitric
How O3 helps repair musculoskeletal tissues (tissue repair)
When O3 gets in contact with organic uids such as plasma,
lymph, urine, and saliva, it interacts highly with all tissue
components.11 It can react with antioxidants, glutathione, cys-
teine, albumin, ribonucleic acid (RNA), and deoxyribonucleic
acid (DNA).12 All these reagents, participate in the ozonation
process and formation of lipid oxidation products and ROSs.11
These two molecules function as biochemical regulators of
inammation and physiological concentrations.11 ROS are
described as being highly unstable, immediate action and a
half-life less than one second.12 It is common that patients re-
port the sensation of well-being during the course of O3 therapy
and this is due to the LOPs which stimulate the central nervous
system and endocrine system while also improving hormonal
production, neurotransmitter release, and metabolism.11 It was
proved that O3 was capable of promoting the preservation and
increase of endogenous antioxidant systems through a study
conducted by Re et al.13 Another study which dealt with the
ozonation of platelet-rich plasma samples results demonstrated
the increase of interleukin (IL)-8. The increase of IL-8 allows
for the leukocytes to leave the circulation into the tissues to
facilitate the phagocytosis of bacteria and necrotic tissue of
ulcers.14 The results also showed an increase in growth factors
such as platelet derived growth factor (PDGF), IL, and trans-
forming growth factor beta (TGF-β) 1.14 Lim et al.15 that when
dermal wounds were exposed to O3, it increased the activity of
factor nuclear kappa B, an important immunomodulatory of
inammation and the expression of TGF-β which is essential
for remodeling tissue.
Temporomandibular joint disorder (myofascial pain syndrome)
The temporomandibular joints are the joints that connect the
jawbone to the skull. Temporomandibular joint disorder also
known as myofascial pain syndrome results in pain that limits
chewing, talking, and other daily activities. It was found that
the use of O3 therapy has been much more effective than medi-
cation therapy in patients with high pain scores which relieves
pain and increases the maximum voluntary interincisal mouth
opening values. A proposed explanation of why O3 causes the
joint to heal quicker than of the traditional therapy is due to the
highly reactive nature of O3. It is able to stimulate the broblas-
tic joint repairing abilities when injected into a joint capsule. It
is also able to promote new cartilage growth as well as reducing
inammation. When split into separate oxygen atoms, O3 is
able to react when in contact with a contaminant.16-18 In fact,
it never fails to initiate this reactive activity. A recent study
found that 87% patients had either improved or completely
recovered from temporomandibular pain.18 It was concluded
that this was a promising new treatment, but the mechanism
of action is still being researched. A plausible mechanism can
be due to a single oxygen atom oxidizing the contaminants. It
is thought that O3 can stimulate the broblastic joint since it is
such a reactive molecule. O3 can react with the contaminant
when it splits into single oxygen atoms.18
Herniated disc (back pain)
The herniated disc is characterized as a condition affecting the
spine in which a tear in the brous ring of an intervertebral
disc allows the central portion to bulge out.19 The treatment of
lumbar disc herniation is applied with a needle which is placed
into the hernia between the inner margin of the facet joint and
the lateral nerve root. This has been considered a minimally
invasive treatment for nerve root treatment since the O3 is mini-
mally invasive and the needle is thin. The mechanism of action
is as follows: nucleur pulposus is oxidized by proteoglycan
which then cause it to denaturize and reduce in volume. The
local blood circulation will have reduced when the osmotic
pressure is reduced. The doze of O3 administered is essential
and should not pass the capacity of glutathione and antioxi-
dant enzymes to prevent accumulation of hydrogen peroxide
and superoxide anion which can possibly degradation of cell
membranes.20 O3 in a medium of pH = 8 or higher will cause
the formation of free radicals. While, in a medium of pH =
7.5 or lower the formation of peroxides occur due to the ozon-
olysis mechanism. In oxygen-O3 therapy, O3 is administered
at a nontoxic concentration of 1 to 40 µg of O3 per milliliter
of oxygen. It was found through in studies that consisted of
in vitro on resected human disk specimens as well as in vivo
on rabbits that the optimal concentration to administer is 27
µg. O3 has a direct effect on the disk’s nucleus pulposus spe-
cically in proteoglycans at this concentration which results
in subsequent cell degradation of the matrix and release of
water molecules.21 The matrix is replaced by brous tissues
and formation of new blood cells in approximately 5 weeks.
A reduction in disk volume is the result of all these events. In
a study conducted by Andreula and others,22 ve histologic
disk specimens were removed during surgical microdiske-
cotmy who received intradiscal injects of O3 at 27 µg/mL.
Dehydration of the brillary matrix of the nucleus pulposus,
signs of regression (fragmentation and vacuole formation), and
revealing collagen bers were all noted in these specimens.
Other ndings of a herniated disk untreated with medical
O3 are proliferating and signs of new blood cell formation
guided by lymphocyte inammatory tissue and chondrocyte
hyperplasia. One of the main therapeutic causes of medical
O3 is a reduction in disk size which can possibly reduce nerve
root compression. Furthermore, disk shrinkage can improve
local microcirculation and increase the supply of oxygen by
reducing venous stasis caused by disk compression of vessels.
O3 therapy also had analgesic and anti-inammatory effects in
treating disk herniation.23 The action ties into inhibiting release
of bradykinin or release of algogenic compounds as well as
inhibiting synthesis of proinammatory prostaglandins. Proin-
ammatory cytokines such as interleukin can be neutralized by
increasing release of antagonists. The results from this study
was satisfactory compared to other percutaneous treatments
for disk herniation such as enzymatic chemonucleolysis.24 The
two procedures are similar, however oxygen-O3 therapy is less
invasive due to the narrow nature of the needle and less trau-
matic.25 Also, there were no anaphylactic or allergic reactions.25
Shoulder (Glenohumeral joint)
The shoulder allows for the role of orientating the hand and
has a great degree of movement.26 Specically, the glenohu-
meral joint is not a stable ball-and-socket joint, but has high
mobility.26 The rotator cuff muscles allow for joint motility.
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These muscles include the infraspinatus, subscapularis, su-
praspinatus, and teres minor. O3 therapy for the glenohumeral
joint includes injection with the posterior approach under the
inferior margin laterally using a 22 G needle. In a case study,
Benvenuti27 reported that a 58-year-old woman experiencing
severely limited joint movement and pain underwent a session
of O3 therapy with 10 mL gas mixture at a concentration of 15
µg/mL. Furthermore, it is helpful to puncture the long head of
the bicep muscle and subacromial bursa with a 27 G needle in
microdoses of 0.5 to 1 mL. After one week, the patient reported
a reduction of nocturnal pain.27 The patient reported a recovery
of active shoulder function and total reduction of pain.
Shoulder adhesive capsulitis
Shoulder adhesive capsulitis is a condition where there is a
reduction in the arc of active motion.28 Adhesive capsulitis is
characterized with an unknown etiology that has an onset of
pain associated with it.28 The treatment with oxygen-O3 can
help in the reduction of pain as well as inammation activ-
ity. It uses a mixture which is 9596% oxygen and 45% O3.
The reduction and modulation of inammation activity and a
reduction of pain are a few of the many action accomplished
with medical O3. The local injection of O3 destroys algogenic
substances, alters serotonin, and inactivates bradykinin. All
of these substances are altered to produce no pain. A release
of soluble receptors or anatagonists neutralize proinamma-
tory cytokines such as interferon-a, tumor necrosis factor-α
(TNF-α) and ILs. In addition, the denaturation of cellular pro-
teins such as kallikrein, kininogen, and cyclooxygenase (COX)
help form endorphins and modify the pain receptors. Another
important activity is given by the muscle relaxant action by
direction action on the muscle bers.12 Contraindication to
this treatment include latent hypoglycemia, hyperthyroidism,
favism, pregnancy, and sickle cell anemia. This study has
many limitations since it was a case study. It can be a basis
for future studies on a better statistical criterion as well as on
more patients.
Hip bursitis (inflammation)
Hip bursitis can be characterized as the swelling of bursae. The
bursae are uid-lled sacs that cushion muscles and tendons.29
The hip is similar to the shoulder since it is also a ball-and-
socket joint. However, the hip has much more exibility in
movement as compared to the shoulder where it is attached
to the trunk. It is common that patients are not aware they
have a hip inammation since they might complain about the
pain in the anterior knee and thigh rather than the hip itself.
O3 therapy can be used to alleviate hip pain due to functional
overload, trochanteric bursitis, pain caused by initial and late
coxarthrosis, and hip tendonitis. It is also helpful to associ-
ate oxygen-O3 therapy along with prescribed exercises and a
period of rehabilitation. In a case report,27 a 54-year-old man
was treated by a cycle of 5 therapy session of O3. The dosage
consisted at a concentration of 25 µg/mL at 55 mL oxygen)
through weekly intervals. It was injected at a lateral approach
where the method of inltration was called peritrochanteric.
The patient referred difculty walking with deambulation
for approximately 50 meters and nocturnal hip pain.27 The
joint pain subsided after the rst treatment session with an
improvement in trochanteric swelling. At the end of the treat-
ment cycle daytime and nighttime pain had disappeared. By
the subsequent follow-up visit which was approximately 5
weeks later, there were no signs of bursitis. Signs of limping
stopped and the patient was able to take the stairs without
any difculty. This study demonstrates the versatility and ef-
cacy of O3 therapy when administered in small doses through
weekly intervals.
Osteoarthritis (OA) (knee)
OA is a degenerative disease that affects function and produces
pain.30 O3 inltration accelerates anabolism and produces
better vascularization on cartilage and bone. Regarding knee
osterarticular disease, there is a great variability in terms of
gas concentration of O3 as well as the side of injection. On the
knee joint, it could be either periarticular, intra articular, and
subcutaneous. Currently, there is no cure for knee OA. Because
of this there is a focus on the amelioration of the symptoms
caused by knee OA. O3 improves the range of motion (ROM)
and slows down the degenerative process. It also is able to
inhibit chondrocytes, stem cells, inammatory cytokines, nitric
oxide, and mineral metalloproteinases. The published studies
on O3 regarding the knee are limited. Riva Sanseverino31 were
the rst people to use O3 to treat the knee OA. Over the many
years, intra articular O3 injections have found to be a costless
procedure that is effective. Patients who have severe OA will
improve at about the same rate as those with low grade OA.
The pathophysiology of OA is characterized by the destruc-
tion and softening of articular cartilage along with increased
matrix degradation due to proteoglycanases and collagenases.
Activated chondrocytes and monocytes release enzymes which
by releasing TNF-α and IL-1 multiply the inammation. The
synthesis of prostaglandins increases and there is an attempt to
maintain biomechanical matrix. It is believed that the synthesis
of O3 Messengers LOPs and ROS would act in two phases
in the synovial uids. O3 would inhibit the proinammatory
cytokines such as prostaglandin E2 (PGE2) during the rst
phase. During the second phase, O3 will act over inhibitory
cytokines such as IL-10, TGF-β, and IL-4, antioxidant en-
zymes, and neoangiogenesis. These are all working together
in the process of repairing the articular joint by stimulating
broblasts, chondrocytes, and stem cells.
Carpal tunnel syndrome
Carpal tunnel syndrome is caused by a compressed nerve in
a narrow passageway on the palm side of the wrist.32 Sec-
ondary forms are associated with a variety of diseases such
as hypothyroidism, diabetes mellitus, oestrogen therapy,
rheumatoid arthritis, amyloid disease.33 The mechanism of
oxygen O3 treatment is based on three mechanisms that are
shared by the treatment of herniated disc in the spine. By
increasing trans-tissue and intra-oxygenation along with
reduced lymphatic stasis and hypoxia, there is an indirect
vessel-mediated decompression of the nerve roots. Second,
by inhibiting the release of polymorphonucleates through in-
creasing immunosuppressive cytokines and proteinase through
macrophages.34 Third, inhibiting the release of prostaglandins
and pro-inammatory bradykinins, action on the cell-mediated
inammatory response would take place.35 Oxygen-O3 therapy
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Medical Gas Research ¦ September ¦ Volume 8 ¦ Issue 3
seems to guarantee improvements of symptoms after one year
compared to steroid injections. A study conducted by Zam-
bello et al.,36 showed that 90% of patients had a signicant
improvement after O3 injection. 17% had a good control of
symptoms and 70% of patients no longer had symptoms after
a one year follow up.36 However, further studies should be
conducted to see if symptoms remain or not after two years
or more to evaluate the long-term effects.
Partial tear of the supraspinatus tendon
The supraspinatus tendon is part of the rotator cuff.37 Oxygen-
O3 therapy is one of the many methods that can be used to
relieve the symptoms. In a study,38 which consisted of 40
patients, specically 26 males and 14 females whom had
shoulder pain for approximately six months. In order for
patients to be included in the study, the size of the tear of the
supraspinatus had to be less than 1.5 cm. Ultrasound guidance
is recommended since the blind inltration does not guarantee
to get properly in the shoulder joint.38 It was concluded that
the ultrasound-guided inltration of oxygen-O3 therapy proved
to be an effective treatment method in partial tears of the
supraspinatus tendon. However, it is necessary to do further
research requiring a large sample size.
Subacromial bursitis
First degree spondylolisthesis and spondylolysis-spondylosis
is a defect of part of the vertebral arch between the superior
and inferior spinal processes. Spondylolisthesis is if the defect
results in a forward shift of one of the vertebral body on one
another.39 Eighty-three percent of the 18 patients in this had a
complete recovery from pain immediately.40 The twofold ac-
tion of O3 in the perganglionic region and in the lysis points
of the neural arch or pars interarticularis region innervated by
Luschka’s recurrent nerve is an explanation for such fast pain.21
The use of the gas mixture directly next to the lysis points on
Luschka’s nerve by exploiting the well-known analgesic and
anti-inammatory effects of the oxygen-ozone mixture. The
spine is innervated by Luschka’s recurrent nerve or posterior
primary branch and vertebral plexus.41 The plexus innervates
the end plates, longitudinal ligament, vertebral bodes, and rela-
tive peridural tissues in the pars interarticularis region or the
neural arch.41 The anti-inammatory and analgesic effects of
the oxygen-O3 mixture inltrates directly proximal to the lysis
point on Luschka’s nerve.42 Prostaglandin levels and cytokine
levels are normalized with a reduction of reactive oxidant
species and an increase in superoxide dismutase production.
A eutrophizing effect occurs when subsequent inltration into
the periganglionic region takes place both adjacent to the nerve
root compressed at the level of muscle spasm and injured by
accompanying disc protrusion.43,44 A good nal outcome is
accounted due to the combined action.
Lumbar facet joint syndrome
Lumbar facet joint syndrome can be described as pain at the
joint between two vertebrae in your spine. It is a condition
which affects about 80% of people who have lower back pain.
The main mechanism of action may be considered as follows:
there is an immediate oxidation by which the proteoglycan
in the nucleus pulposus could be oxidized immediately and
the osmotic pressure is reduced.45 The volume of the nucleus
pulposus would decrease as well as necrotize, denaturize, and
atrophy. The local blood circulation would also be changed
when the osmotic pressure is reduced. The symptoms may be
improved when increasing the oxygen supply. Regarding the
anti-inammatory effect, as the vein, lymphoid tissue, and
nerve root were compressed by the annulus brosus and herni-
ated nucleus pulposus, the lymphatic backow and venous was
obstructed which was accompanied by exudation and nerve
edema. To induce an immune response, antigenic substances
such as B-lipoprotein and glycoprotein could be released that
would result in aseptic inammation and adhesion. The pain of
disc herniation could be caused by these factors. Lastly regard-
ing the analgesic effects, enzyme products and inammatory
mediators stimulate the nerve endings near ligament and on
the disc surface that causes the pain that is associated with disc
herniation. In order to attain pain relief, the strong oxidative
activity of O3 can inactivate the above inammatory mediators.
O3 injected into the middle of the disc through the conventional
posteriorlateral route had produced the desired result for small
or medium size disc herniations.22 Regarding the large disc
herniation, the symptoms were not eliminated quickly and the
efcacy was limited due to the hernia compressing the nerve
root. The efcacy of O3 therapy is poor with patients who have
large lumbar disc herniation and greatly signicant with those
who have a small or minimal disc herniation. Since the annulus
brosus was either completely or partially ruptured, it was
found that the O3 could diffuse through the tissues that were
torn surround the vertebral or spinal disc. This would cause
the hernia and nucleus pulposus to not be fully oxidized. In a
study conducted by Lu et al.,46 the treatment of large lumbar
disc herniation with percutaneous O3 injection was greatly
effective. An improvement of local ablation and eliminating
local aseptic inammation was achieved through O3 injection
in or around the hernia areas. Therefore, it was concluded
through using percutaneous O3 injection with the inner margin
of facet via the posterior-lateral was an effective method. It
is important to note that the concentration of O3 should be
acceptable in quantity and the rupture of the annulus brosus
by high intradiscal pressure should be avoided in order to
ensure efcacy. Low pressure of repeated injection of O3 was
suggested for large disc herniation. This can be accomplished
by repeatedly pushing and pulling the syringe to allow the O3
to completely oxidize and contact the nucleus pulposus. New
O3 is then injected and the residual O3 is abandoned to avoid
rupture of the annulus brosus.
Cervical disc herniation
Cervical disc herniation is wear and tear of a disc in the neck.
It is suggested that the material from the nucleus pulposus may
act as a chemical or immunologic irritant the nerve and these
mechanisms may produce an inammatory effect.47 Studies
have hypothesized that the injection of O3 induces overexpres-
sion of antioxidant enzymes which then neutralizes excessive
ROS formation. In the degenerated nucleus pulposus, the
intradiscal injection of O3 can accelerate the degradation of
proteoglycans.14 The biochemical modication of the medium
in the extraduralspace is one of the important aspects of it.48
The cause of radicular pain is A2 phopholipase independent
of a direct inammatory process or immunological response.47
A2 phospholipase is responsible for the prostaglandins and
arachidonic acid liberation. It has been shown that there are
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high levels of A2 phospholipase in herniated discs. A power-
ful stimulus to the activation of antioxidant defense is the
result of O3 injected in the peridural space of the conjugation
foramen and disc. Even in cases that had extruded cervical
disc pathology, injections were still performed and had great
results. This is most likely due to the fact that normal tissues
and the isolate fragment are separated.48
Rheumatoid arthritis
Rheumatoid arthritis is characterized as an autoimmune dis-
ease where the body’s immune system attacks the joints instead
of bacteria and viruses.49 The syndromes include hyperplasia
of synovial cells, excess synovial uid, and forming pannus
which can damage joint deformities and articular cartilage.50,51
The etiology for rheumatoid arthritis is still not understood.
The common treatments are immunologic purging, advanced
surgical treatment, and drug therapy.52 However, O3 therapy is
a new treatment in treating rheumatoid arthritis can overcome
these limitations at a certain level. The therapeutic mechanism
of O3 still remains unclear. Previous research has showed
that O3 can reduce the activity of TNF-α in the inammatory
tissues and suppress synovial hyperplasia and joint swell in
rheumatoid arthritis in rats.53,54 Therefore, a study was con-
ducted to treat bovine collagen II-induced RA in rats with
intraarticular injection of O3 at various concentrations.55 Rats
were injected with complete Fruend’s adjuvant bovine col-
lagen II that successful established a rat model of rheumatoid
arthritis.55 In the O3 treated groups, the optimal concentration
for treating rheumatoid arthritis was 40 µg/mL.55 They also had
higher TNF-receptor (TNF-R)1 indicating that O3 can reduce
synovium injury in rats with RA and lower synovial TNF-α
and TNF-R2 levels.55 A plausible mechanism is the reduction
in TNF-R1 and rheumatoid arthritis TNF-a levels and increase
the level of TNF-R1 which increase synovial cell apoptosis
and preventing synovial cell proliferation.55
Systemic sclerosis
Systemic sclerosis is a chronic tissue disease characterized by
vascular abnormalities in the joints, internal organs, and bro-
sis.56 The etiology and clinical manifestations of scleroderma
are still not understood; this is why it is difcult to treat sys-
temic sclerosis.56 The inammatory processes can be limited by
O3’s potential in reducing the proliferation of neutrophils and
mastocytes, increasing concentration of prostacyclin 6-keto-
prostaglandin F1α (6-keto-PGF1α), impeding the release of
acute phase proteins, and decreasing the concentration of
prostacyclin (PGF)2α resulting from the oxygen radicals on
arachidonic acid.57 The results from this study have proved
to slow down the progression of the illness by limiting the
activation of the immune system. It had also increased the
movability of interphalanx joints and decreased the thickness
of the skin.57 O3 is able to penetrate the epidermis water-fat
barrier and also has a good solubility in serum which is why
it has a good effect on the skin.57 The vasodilating effect of O3
allows for the decrease of skin score index, decrease of arterial
blood pressure, increase in angle of interphalangeal joints all
through the synthesis of nitric oxide synthase.57
Fibromyalgia is seen as a rheumatic disease which means that
it causes myofascial pain or soft tissue pain.58 The mechanism
of O3 is as follows. After the O3comes into contact with the
blood, it immediately reacts with various reducing molecules
such as antioxidizing agents, unsaturated fatty acids containing
double bonds to produce reactive oxygen species. Both lipid
peroxidation products and hydrogen peroxide are generated,
when O3 reacts with polyunsaturated fatty acid (PUFA).59
Enzymatic antioxidant systems such as aldehyde dehydro-
genase and glutathione-transferase neutralize the toxicity
of both molecules (LP and hydrogen peroxide). They act as
secondary messengers which stimulate further generation of
antioxidant enzymes.60 This can be done if O3 is administered
in quantities that are able to achieve a therapeutic effect which
can protect against radicals and is nontoxic. A case which a
45-year-old woman was administered oxygen-O3 therapy
biweekly sessions equating to a total of 12 sessions. Due to a
lowering of painful symptoms, the patients experience a sense
of well-being. An improvement in the asthenia was seen due to
a greater oxygenation of tissues because of O3. There were no
side effects seen in this case. The limitation from this study is
the small number of patients in which it was conducted. It was
found that O3 glycolysis was sped up through the activation of
the mitochondrial respiratory chain.61,62 The O3 mixture will
cause an increase in oxygenation level due to the increased
efciency of the antioxidant enzyme system, enhance sero-
tonin production, and microcirculation. The production of
endorphins was enhanced by the motor plate. So patients who
had bromyalgia had improved their daily activities by 40%
and sleeping disorders by 6%.63
Muscle oxygenation
The role of O3 therapy was observed for hypoxic tissues, those
in which tissues were below-normal level of an adequate oxy-
gen supply.64 A study has demonstrated that O3 therapy can
change the level of oxygenation in resting muscles by measur-
ing directly the pressure of oxygen.64 Through autohemotrans-
fusion, O3 therapy avoids lung toxicity from oxidative stress.
The effects of O3 are mediated by rapid oxidation of blood
substances. Hydrogen peroxide and peroxidated lipoproteins
both are reactive oxygen species that can activate the hexose
monophosphate shunt. Charge modication is done by the in-
crease of malonyl aldehyde and lipid peroxidation as well as an
improvement of blood rheology and exibility of erythrocyte
membrane. The collaboration of nitric oxide, adenosine, and
prostaglandins can decrease vascular resistance. It is hypoth-
esized that this will lead to blood ow redistribution. This is
supported by the data collected in the study which shows the
correlation between the change in pressure of oxygen post-
ozone therapy and the initial oxygenation. Another possible
mechanism to explain the results of this experiment, is the
increase in production of 2,3-diphosphoglycerate in erythro-
cytes and lipid peroxidation of red blood cell membranes can
be achieved with the activation of the hexose monophosphate
shunt.65 These would both cause a shift to the right in the
oxyhemoglobin dissociation curve ultimately leading to an
increase of release of oxygen to the tissues.65
Spinal muscle disorder (horse)
The harmonious movement of the spine and balance are the
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Seyam et al. / Med Gas Res
Medical Gas Research ¦ September ¦ Volume 8 ¦ Issue 3
result of the muscles running along the spine to the dock of
the tail. Muscle fatigue is caused by soft tissue spinal lesions.
Impaired performance in athletic horses is mainly caused by
changes in the thoracolumbar spine. One of the many patho-
logic changes affecting the thoracolumbar spine is soft tissue
spinal lesions. The muscles may suffer varying degrees of
inammation after intense muscular stress. In the study con-
ducted, all four horses had a positive response to O3 therapy.66
They were all able to increase their trotting speed due to the
stiffness that was relieved and increase in posterior muscle
chain thrust. The mechanism of action of O3 is described as
the O3 coming in contact with the blood on different targets.
Since O3 is very active it reacts when it comes in to contact
with blood or any biological uid. O3 rst reacts with polyun-
saturated fatty acids then with proteins, antioxidants (ascorbic
acid and glutathione). When O3 reacts with bio molecules, it
produces a molecule of ROS which is hydrogen peroxide and
two molecules of lipid oxidation products. The ROS activates
the pentose phosphate pathway. The lipid oxidation products
that are produced as 4-hydroxynonenal and malonaldehyde.67
Since they are toxic, they undergo a dilution in the circula-
tion and get metabolized in the blood circulation. Overall, the
benecial effects seen by O3 therapy is the increase in avail-
ability and delivery of oxygen, adenosine triphosphate (ATP),
and glucose within ischemic tissues, enhances implantation of
bone marrow stem cells at the site of lesion which can provide
neovascularization, tissue regeneration, and angiogenesis.
Ballardini66 did not notice any short or long-term effects when
administering different treatment cycles to the same horse; he
always noticed a positive response from the horse.
Spinal pain
About 80% of the world’s population has a symptom of low
back pain.68 In general, the pain one suffers from a herniated
disc is caused from inammation and not compression. The
use of O3 therapy is recommended to treat back pain before
doing any surgical procedures. There are two techniques one
can attempt: direct approach and the indirect approach. O3
acting as a chemical reactant by needle insertion refers to the
indirect approach. Whereas, the direct approach is done by
direct insufation of the oxygen-O3 mixture of a concentration
at approximately 30 µg/mL and preceded by needle insertion
in the pathologic intersomatic space. Eighty percent of 63,000
patients have shown good outcomes conrmed by magnetic
resonance imaging (MRI) controls and computed tomogra-
phy.48,69 In the future, it is essential to conduct more studies
to assess the role of variables such as place of needle, needle
type, O3 concentration, and oxygen amount. The mechanism
of action underlying O3 therapy for the direct method is: O3
reacts with biomolecules when dissolved in interstitial water,
which then results in the formation of reactive oxygen spe-
cies such as hydrogen peroxide and hydroxyl radicals.70,71
The matrix degenerates with disappearance of the herniated
material, when ROS reacts with proteoglycans of the nucleus
pulposus,72 thusleading to a lower of sensitivity of axons.
Alternatively, nociceptors can be stimulated when algesic
endogenous substances released during perineural ischemia.
The indirect approach consists of one to four injection of 510
mL of O3. The disappearance of pain because of the complex
series and chemical and neurological reactions have dened
it as a chemical acupuncture. The O3 concentration must be
between 1825 µg/mL.73 If it is higher than 20 µg/mL, it can
be too painful, and if it is too low, then it won’t be effective.
Therefore, it is essential to maintain the right balance since it
can cause risky vasovagal reex and lipothymia during initial
treatments. Contrarily, the pain threshold rises after ve to
seven treatments therefore, the concentration of O3 increases,
but must not exceed 30 µg/mL. The inltration of O3 therapy
uses the paravertebral muscles as a route. Regarding the indi-
rect method, the mechanism of action underlying O3 therapy is
described as O3 reacting with PUFA, LOPs, and anti-oxidants.
The nal therapeutic effect is achieved with these compounds
stimulating local C-nociceptors. Altogether, it is concluded
that injection of O3 either into the paravertebral muscles or
intradiscally has indicated long-term pain relief.16,74
Lumbar spinal stenosis (LSS)
LSS can be characterized as the narrowing of the spinal ca-
nal of the lumbar area.75 The three main symptoms that LSS
gives rise to are radicular pain or discomfort, low back pain,
and neurological intermittent claudication.O3 therapy blocks
phospholipase A2 which is the same enzyme that epidural
steroid injections target.76-78 Therefore, O3 can serve as a better
substitute steroid since it has the same mechanism of action
while being a much safer drug. The neurological pain in LSS
can be improved by the microcirculation that O3 induces.79
In a study conducted by Baeza-Noci,76 patients with spinal
stenosis underwent O3 therapy for 10 biweekly sessions along
with 5 weekly sessions. Each injection of O3 (10 mL) had a
concentration of 20 μg/mL. After 1 year, from the baseline,
74% of patients improved with excellent results.76
Complications of O3 therapy in musculoskeletal disorders
The reactivity of O3 gives rise to a cascade of reactions such
as the lipid ozonation products acting as signal transducer
molecules, peroxidation of lipids leading to changes in mem-
brane permeability.80 Endogenous mediators of inammation
are released by the activation of lipases through which LOP
activates the lipases.81,82 It is the O3 which reacts with unsatu-
rated fatty acids such as in the pulmonary cell bilayers and
lung lining uid. Enzyme inactivation occurs when there is a
loss of functional groups in enzymes. Cell death or cell injury
may occur from these reactions. Hazardous effects on lung
alveoli can occur with the combination of nitrogen dioxide
(NO2) and O3 that are in photochemical smog. These effects
can be prevented by free radical scavengers such as vitamin
E, C or dietary antioxidants. In an in vitro study, peroxides
were found to be formed by the presence of O3 and oxidized
arachidonic acid.83 The activity of prostaglandin endoperoxides
are comprimable to that of arachidonic acid peroxides. The
aggregation of human platelets in platelet-rich plasma was
seen with arachidonic acid peroxides. While, the presence of
vitamin E and indomethacin, presented no signs of aggrega-
tion of human platelets in platelet-rich plasma.83 Therefore,
this suggests that they can treat O3 toxicity.
O3 therapy is becoming an effective treatment option for
musculoskeletal disorders as it promotes tissue hyperoxygen-
ation as well as treating painful syndromes affecting muscles,
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Medical Gas Research ¦ September ¦ Volume 8 ¦ Issue 3 109
Seyam et al. / Med Gas Res
tendons, and joints. Though O3 has indicated great success in
most indications mentioned in this review, there still needs
to be further research conducted to determine its activity for
treatment of plantar fasciitis, costochondritis, and myofascial
syndrome. In order to prevent the common side effects that
O3 therapy causes, it is essential to continue researching the
utility of O3 therapy in all indications.
The authors are thankful to Drs. Kelly Warren, Todd Miller, and
Peter Brink (Department of Physiology and Biophysics, Stony
Brook University School of Medicine, Stony Brook, NY, USA) for
departmental support, as well as Mrs. Wendy Isser and Ms. Grace
Garey (Northport VA Medical Center Library, Northport, NY, USA)
for literature retrieval.
Author contributions
OS designed, organized, and wrote the review article; designed the
outline; solved queries related to scientic publications from the
journals. NLS performed Medline searches, aided in writing the
review article and critiqued the literature. IR revised the article to
add logical reasoning and corrected the literature. JG critiqued and
applied logical reasoning to the literature. WJ critiqued and applied
logical reasoning to the literature. SAK formulated clinical concepts,
reviewed the article, and corrected the reference. All authors have read
and approved the manuscript provided.
Conflicts of interest
The authors have no conicts of interests to declare.
Financial support
Copyright license agreement
The Copyright License Agreement has been signed by all authors
before publication.
Plagiarism check
Checked twice by iThenticate.
Peer review
Externally peer reviewed.
Open access statement
This is an open access journal, and articles are distributed under
the terms of the Creative Commons Attribution-NonCommercial-
ShareAlike 4.0 License, which allows others to remix, tweak, and
build upon the work non-commercially, as long as appropriate credit
is given and the new creations are licensed under the identical terms.
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Nemoto Edwin, University of New Mexico Health Sciences Center,
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Received: 2018-05-30
Accepted: 2018-08-09
C-Editor: Yang LJ, Zhao M; S-Editor: Yu J;
L-Editor: Wang L;
T-Editor: Jia Y
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... 27 The data from numerous published studies have confirmed the effectiveness of the ozone therapy for lower back treatment with or without sciatica. 3,25,47,48 Other studies compared the efficacy of analgesia and the duration of remission in patients with different courses of treatment: the use of ozone therapy-only vs. pharmacotherapy. 27,35 Thus, the first group underwent a local intra-foraminal or a peridural administration of steroids, and in the second group -a local administration of the oxygen-ozone mixture. ...
... The studies provided a sufficient evidence of both short-and long-term pain control with minimal side effects. 3,29,48 ...
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Introduction Low back pain is one of the most common causes of short-term, and sometimes long-term, disability in the population younger than 45 years old. Approximately 60% to 80% of the population in developed countries experience back pain in various locations (neck, mid and lower back) at least once in their lifetime. Guidelines regarding back pain treatment are undergoing constant modifications and improvements. The relevance of dorsalgia as a significant medical problem and its management is shown by the increased number of recently published papers, which has tripled in the past several years (from 22% to 65%). Aim To analyze the most critical risk factors of the degenerative intervertebral disk disease, and to review the effectiveness of invasive and noninvasive methods of treatment of the lower back pain syndrome. Material and methods Recently published papers focusing on invasive and noninvasive treatments of low back pain syndrome. Results and discussion Surgical intervention as a single method of back pain treatment is indicated in a small number of cases. The risk of repeated surgeries for intravertebral disk herniation should be considered before any surgical intervention. A wide variety of treatment options allows to choose the most effective approach based on individual needs. Conclusions Conservative, noninvasive approach has shown to be an effective alternative for lower back pain and radiculopathy treatment. It has been determined that ozone therapy is an appropriate, relevant, and affordable treatment method for patients with vertebral degenerative changes and intravertebral disk diseases.
... These molecules function as biochemical regulators of inflammation through the downregulation of the tumor necrosis factor, as well as tumor necrosis factor receptor 2 [5]. Ozone therapy also has an analgesic effect, which raises the pain threshold by activating serotonin-mediated pathways to release endogenous opioids [6]. Due to the absence of adverse effects or major complications, many studies support its use in treating myofascial pain syndromes and piriformis syndrome [7]. ...
... Ozone not only stimulates the central nervous and endocrine systems, but also improves hormonal production, neurotransmitter release, and metabolism, leading to an increase in pain threshold [32,33]. Ozone therapy also increases the production of lipid oxidation products and endogenous antioxidants; moreover, it raises the serum level of interleukin 8, which promotes the phagocytosis of bacteria and necrotic tissue and aids tissue healing [6]. Furthermore, ozone inhibits the production of inflammatory prostaglandins by modifying the breakdown of arachidonic acid and kick-starts the healing process by activating fibroblasts [34]. ...
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Lin, J.-A.; Galluccio, F.; et al. Efficacy of Ultrasound-Guided Injection of Botulinum Toxin, Ozone, and Lidocaine in Piriformis Syndrome. Healthcare 2023, 11, 95. https://doi. Abstract: Background: Piriformis syndrome (PS) is a painful musculoskeletal condition characterized by a deep gluteal pain that may radiate to the posterior thigh and leg. This study was designed to compare the effectiveness of ozone and BTX to lidocaine injection in treating piriformis syndrome that was resistant to medication and/or physical therapy. Study design: Between November 2018 and August 2019, we involved eighty-four subjects diagnosed with piriformis syndrome in a double-blinded, prospective, randomized comparative study to receive an ultrasound-guided injection of lidocaine (control group), botulinum toxin A, or local ozone (28 patients each group) in the belly of the piriformis muscle. Pain condition evaluated by the visual analog score (VAS) was used as a primary outcome, and the Oswestry Disability Index (ODI) as a secondary outcome, before, at one month, two months, three months, and six months following the injection. Results: The majority (58.3%) of patients were male, while (41.7%) were female. At one month, a highly significant decrease occurred in VAS and ODI in the lidocaine and ozone groups compared to the botulinum toxin group (p < 0.001). At six months, there was a highly significant decrease in VAS and ODI in the botulinum toxin group compared to the lidocaine and ozone groups (p < 0.001). Conclusion: Botulinum toxin may assist in the medium-and long-term management of piriformis syndrome, while lidocaine injection and ozone therapy may help short-term treatment in patients not responding to conservative treatment and physiotherapy. Healthcare 2023, 11, 95. Healthcare 2023, 11, 95 2 of 11
... O 3 reacts with any electron donor that undergoes oxidation, generating O 3 -(radical anion), which decomposes into a hydroxyl radical, also forming a dioxygen molecule. Thus, this reaction makes O 3 a potent oxidant that can act as a precursor to a series of radicals, with actions both in vitro and in vivo 12,13 . O 3 in vivo is safe, regardless of administration 11 : topical, infusions and drinking water, using the techniques of autohemotransfusion, intramuscular, intradiscal, paravertebral, rectal insufflation, and skin exposure [13][14][15][16] , being characterized as systemic. ...
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To evaluate the effect of isolated supplementation of low-concentration ozonized water on the clinical, anthropometric, and inflammatory profile in apparently healthy individuals. A randomized, double-blind, placebo-controlled clinical trial study to evaluate the effects of ozonized water supplementation in two concentrations (10µg/day and 16µg/day) in short-term (7days). Were performed with 66 male and female, over 18 years old. Anthropometric and clinical parameters were measured, serum levels of nitric oxide, manganese superoxide dismutase, glutathione peroxidase were assessed in serum using an immunoassay-ELISA. With average age of 24.2 years, composed of 54.2% males, 35.4% were undergoing hormone therapy and only 31.2% knew ozonized water. Anthropometrics, clinical and oxidative stress characteristics of study participants did not difference significant to time by group interaction (p>0.05). Supplementation of ozonated water in apparently healthy individuals has no short-term effects on evaluated parameters on anthropometric, clinical, and oxidative stress parameters.
... The reduction in herniated disk volume is one of the therapeutic aims of intradiscal administration of medical ozone, as disk shrinkage may reduce nerve root compression. Several previous studies addressed the subject of volume changes in test animals such as pigs, dogs, and rabbits (5) . ...
... Furthermore, Ozone therapy also down regulates TNF and TNFR2 which are in ammatory mediators and it induces an analgesic effect through phosphodiesterase A2 blockage [21]. Ozone therapy is presently making great progress in the treatment of musculoskeletal diseases including shoulder joints both in shoulder adhesive capsulitis sub acromial bursitis, hip bursitis, rheumatoid arthritis, herniated disc, lumbar facet joint syndrome, carpal tunnel syndrome, osteoarthritis, and others [23]. ...
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Background Chronic musculoskeletal pain is multifaceted and20% of the adult population lives with severe chronic pain and have negative consequences, intense pain, depression, weakness, sleep problems, loss of enjoyment of life and decreased emotional well-being. This work done to study efficacy of trigger point injections with ozone for treatment of chronic musculoskeletal pain in patients with abnormal mitochondrial redox state compared to standard steroid injection or combination therapy. Methods This is a prospective randomized clinical study conducted on 51 patients with chronic musculoskeletal pain at Medical Research Institute Hospital, Alexandria University from January2019toJanuary2021.Patients randomly using computer-generated random numbers into 3groups,17received ozone injection,17betamethasone injection and17 combined Ozone and betamethasone injection. Groups were compared regarding intensity of pain, correction of mitochondrial redox state and normalizing Lactate/Pyruvate ratio. Results there were differences between 3groups as regard VAS;three days after intervention(p < 0.021)as it was lower in group A compared to group and at one and three weeks after intervention(p < 0.001)where it was lower in groups A,C when compared with groupB.There were differences in lactate/pyruvate ratio(percentage change)between the 3 groups(p < 0.004)as it was lower in groups AandC when compared with groupB.There were differences between 3 groups as regard mitochondrial copy number(p < 0.002)as it was higher in group A when compared with groupB.There were differences between the 3 groups as regard reduced/oxidized glutathione(p > 0.008)as it was higher in groups AandC when compared with group B. Conclusions Trigger point injections with ozone can relief musculoskeletal pain as it had significant effect in reduction of muscle pain and increasing pain free interval. Pain improvement increases with time. Ozone improves muscle oxygenation, mitochondrial function
... Pharmacological and non-pharmacological therapies are commonly used to reduce pain and improve the quality of life [2]. Concerning new therapies, ozone (O 3 ) could be an effective treatment option for musculoskeletal disorders and painful syndromes affecting muscles, tendons, and joints [3]. Ozone is a natural gas, first used in medicine for the antimicrobial treatment of wounds during the First World War, and nowadays, it is used in many areas of medicine [4]. ...
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This prospective, open-label clinical study was carried out to evaluate both the efficacy and safety of intramuscular paravertebral injections of an oxygen–ozone (O2–O3) mixture in patients with cervicobrachial pain. We enrolled 540 subjects affected by cervicobrachial pain referred to the Ozone Therapy Ambulatory at the Mater Domini Hospital of Catanzaro (Italy) and to the Center of Pain in Taurianova (Reggio Calabria, Italy). All the subjects (n = 540) completed the treatment and the follow-up visits. The subjects received a mean of 11 cervical intramuscular treatments with an O2–O3 mixture (5 mL) with an O3 concentration of 10 μg/mL bis a week. The improvement of pain was measured by a change in the mean of the Visual Analog Scale (VAS) score from baseline to the end of treatment and during follow-ups. Patient satisfaction was assessed at the end of treatment using the SF-36 Questionnaire. The development of adverse drug reactions was recorded. The mean (±standard deviation) VAS pain score at baseline, at the end of treatment, and during follow-ups showed a significant reduction in pain over time (p < 0.001). All the patients who were enrolled (n: 540) were pain-free after one year. According to the pain distribution, all subjects showed a significant reduction in pain over time in each group (p < 0.05). No significant differences were observed with respect to sex or age. No adverse events were observed during the study. In conclusion, we documented that the intramuscular injection of an O2–O3 mixture is an effective and safe treatment option for patients with cervicobrachial pain.
... studies have noted that ozone can also stimulat endothelial cells and tendon cells to produce a certain biochemical mechanism, inhibit osteoblast differentiation, osteocalcin expression and calci cation of osteoblasts, and accelerates absorption of calci ed deposits [38].Because of these characteristics, ozone therapy has been used in various degenerative and in ammatory musculoskeletal diseases, and it is considered as a complementary and low-risk treatment. Several clinical studies have reported positive results in the treatment of shoulder diseases such as subacromial bursitis, calci ed tendinitis, and rotator cuff tears [39,16].At present, there is no report of allergy or destructive side effects on tendons or cartilage caused by ozone, which can be safely used in patients with diabetes, hypertension and so on [40].What's more, its bene cial effect sustained for a long time,even for 10 years after intervention [40,41].In contrast, despite effective in the short term, steroid injection for tendon disease is not bene cial in the long term, which may explain the recurrence of shoulder symptoms after UGPL.Thus, through the study, we hope to provide clinicians with high-quality evidence of ozone therapy for RCCT and provide effective treatment methods for such patients. ...
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Background: Steroid injection after percutaneous irrigation of calcific deposits is a common method for treatment of rotator cuff calcifific tendinitis(RCCT). However, steroid may prevent calcification resorption and cause potential irreversible damage to tendons. Recent studies have confirmed the positive effects of ozone injection in shoulder tendinopathies,but the application in RCCT has not been reported.Thus, our study aims to evaluate the non-inferiority of ozone versus steroid injection. Methods: This is a prospective, randomized, parallel control and non-inferiority trial. A total of 100 patients with unilateral symptomatic RCCT will be enrolled and randomised in a 1:1 ratio to two groups: ultrasound-guided injection with ozone or corticosteroid.The primary outcome is the numeric rating scale for pain(NRS) at 1 week and 3 months following the procedure. Secondary outcomes include multi- dimensional evaluation of shoulder disability and quality of life improvement,degree of calcification absorption after treatment and the number of multiple treatments. Discussion: The results of this study will provide short-term and long-term evidence for ozone treatment of RCCT in relieving pain or improving shoulder function. Trial registration: Chinese Clinical Trial Registry ChiCTR2200063469.Registered on 7 September 2022.
... Literatürde bu alanda bulunan derlemeler, güncelliğini yitirmiş ya da bel ağrısının pek çok sebebini birlikte ele alan fazlasıyla geniş kapsamlı niteliktedir (7)(8)(9)(10). Bu nedenle, kullanımı giderek yaygınlaşmakta olan OT'nin LDH tedavisindeki etkinliğini araştıran sadece randomize kontrollü klinik araştırmaların ele alındığı yüksek nitelikli ve güncel bir derlemeye ihtiyaç olduğu saptanmıştır. ...
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Amaç: Ozon terapi, lumbar disk hernisi tedavisinde, intradiskal enjeksiyon ve paravertebral kas içi enjeksiyon yolları ile yaygın şekilde kullanılmaktadır. Bu sistematik derlemenin amacı, lumbar disk herniasyonu tedavisinde ozon tedavisinin etkinliğinin randomize kontrollü çalışma sonuçlarına göre değerlendirilmesidir. Gereç ve Yöntem: Pubmed, Google Akademik ve Science Direct veritabanlarında yapılan arama sonucunda elde edilen 105 makale incelenmiş, içlerinden 9 adet randomize kontrollü araştırma sistematik derleme kapsamına alınmıştır. Bulgular: Araştırmalarda ozonun intradiskal ya da paravertebral yolla, 20 µg/ml ile 60 µg/ml arasında değişen konsantrasyonlarda kullanıldığı görülmüştür. Araştırmalarda sadece ozon uygulaması yapılabildiği gibi, bazı araştırmalar ozon injeksiyonunun etkisini başka tedavi yöntemleriyle kombinasyon halinde kullandığı saptanmıştır. Araştırmaların öncelikli çıktı ölçütü olarak ağrının görsel analog skala ile ölçüldüğü görülmüştür. Sonuç: Randomize kontrollü çalışma sonuçları, ozon terapinin lumbar disk hernisi tedavisinde konvansiyonel ilaç tedavisine kıyasla daha etkin sonuçlar vermekte, diğer minimal invaziv tedavilere eklendiğinde ise tedavi etkinliğini artırmaktadır. Ayrıca cerrahiye kıyasla daha az hastanede yatış süresine ve daha düşük tedavi maliyetine yol açmaktadır.
... 33 As it is a soluble gas, once in the blood plasma, it is able to rapidly release reactive oxygen species and lipid oxidation products, sequencing an endogenous cascade and moderate oxidative stress. 34 At this point, an inflammatory cascade is released by leukocytes activation. Inflammatory cytokines, growth factors, proteins are rapidly activated. ...
Extensive bone loss is often experienced in the treatment of trauma, tumors, infections, congenital diseases, and disuse. Autologous bone grafting is considered the gold standard for solving these demands due to its osteogenic, osteoinductive, and osteoconductive characteristics. Thus, the need more surgical sites, volumetric limitations, risk of infections, and in some situations, the cost of hospitalization should be considered. 3D printing biomanufatured calcium phosphate-based scaffolds raises as osteoconductive materials for bone reconstructions. Volumetric disposability, biocompatible performance and easy handling are some benefits of these new options. Advances in biology and tissue engineering technologies are making it possible to use materials and techniques together to achieve better results. Osteogenic properties of ozone are being mapped which make this material a possible biofunctionalizer 3D scaffolds and other materials for tissue engineering. Thus, deficiencies such as the osteogenic potential and remodeling ability of the scaffolds still remains as limitations. Ozone therapy has been used as adjuvant in regeneration and repair processes by releasing free oxygen and increasing the responsiveness of cellular metabolism and generation of vital energy. Therefore, the release responses of inflammatory mediators, growth factors, and cytokines become more effective, especially in situations in which they are deficient, such as at advanced ages. The objective of this literature review is to evaluate the role of ozone therapy to optimize cellular response for the local response of bone formation at critical size defect sites reconstructed with 3D biomanufacturing scaffolds.
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Over the past decade experts repeatedly warned it was but a matter of time before the next pandemic struck. They urged governmental agencies to prepare strategies to diminish its potential impact. When SARS-CoV-2 finally emerged in late January, 2020 the government was paralyzed and unable to take effective action.
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Introduction: Systemic sclerosis is a rare and progressive multisystem autoimmune disorder that is characterized pathologically by vascular abnormalities, connective tissue sclerosis and atrophy of skin and various internal organs (e.g., alimentary tract, lungs, heart, kidney, CNS), and autoantibodies. With an unknown etiology, Scleroderma is a complex polygenetic disease. A recent Genome Wide Association Study (GWAS) confirmed a strong association with the Major Histocompatibility Complex (MHC) and autoimmunity. We provide a case scenario along with a review of the systems involved and challenges physicians can face in dealing with this rare disease. Case presentation: Our patient, a known case of systemic sclerosis, was admitted with a history of right femur fracture following a fall. We highlight the medical, anesthetic and surgical challenges faced by our team in the management of this patient. We will explain the stages patient faced in treatment process till her death. We combined the case report with detailed literature review of this rare disease. Discussion: Systemic sclerosis is a complex disease process with many different levels of system involvement. Patient needs to be reviewed thoroughly in preoperative period by multidisciplinary team and counseled in detail about the difficulties in procedure, risks and complications. Conclusion: Patient with scleroderma presents a challenge to the surgical team and anesthetist and a multidisciplinary approach should be followed with all of these patients to avoid catastrophic results.
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Objective The aim of the trial was to determine the effectiveness of oxygen-ozone injections on knee osteoarthritis concerning pain reduction, joint functional improvement, and quality of life. Methods In this randomized, double-blinded, placebo controlled clinical trial, 98 patients with symptomatic knee osteoarthritis (OA) were randomized into two groups receiving intra-articular 20 μg/ml of ozone (OZ) or placebo (PBO) for 8 weeks. The efficacy outcomes for knee OA were the Visual Analogue Scale (VAS), Lequesne Index, Timed Up and Go Test (TUG Test), SF-36, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Geriatric Pain Measure (GPM). Results After 8 weeks of treatment, ozone was more effective than the placebo: VAS [mean difference (MD) = 2.16, p < 0.003 (CI 95% 0.42–3.89)], GPM [MD = 18.94, p < 0.004 (CI 95% 3.43–34.44)], LEQ [MD = 4.05, p < 0.001 (CI 95% 1.10–7.00)], WOMAC (P) [median of diff = 9.999, p = 0.019 (CI 95% 0.000–15.000)], WOMAC (JS) [median of diff = 12.499, p < 0.001 (CI 95% 0.000–12.500)], WOMAC (PF) = [median of diff = 11.760, p = 0.003 (CI 95% 4.409–19.119)], TUG (no statistical difference) and SF-36 (FC) [(MD = -25.82, p < 0.001 (CI 95% 33.65–17.99)], SF-36 (PH) [MD = -40.82, p < 0.001 (CI 95% -54.48–27.17)], SF-36 (GSH) [MD = -3.38, p < 0.001 (CI 95% -4.83–1.93)], SF-36 (SA) [MD = 2.17, p < 0.001 (CI 95% -19.67–8.24), SF-36 (EA) [MD = -35.37, p < 0.001 (CI 95% -48.86–21.89)]. Adverse events occurred in 3 patients (2 in the placebo group and 1 in the ozone group) and included only puncture accidents. Conclusions The study confirms the efficacy of ozone concerning pain relief, functional improvement, and quality of life in patients with knee osteoarthritis. Trial registration International Standard Randomized Controlled Trial Number Register ISRCTNR55861167
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Objective. Treatment of scleroderma is challenging and limited. The aim of our study was to evaluate the usefulness of thermography in assessment of the clinical condition (joints movability and skin thickness) in clinically advanced patients with systemic sclerosis before and after ozone therapy. Method. The study included 42 patients aged 32 to 73 years with advanced systemic sclerosis hospitalized in the university clinic between 2003 and 2006. Thermography and clinical examinations were conducted at baseline and after two series of bath in water with ozone. Results. The comparison of results showed significant increase in skin temperature by 2.5°C, significant increase in interphalangeal joints movability by 18 degrees, and significant decrease in skin score by 14.7 points. The skin temperature was correlated with skin score ( r=-0.59 ) and joints movability ( r=+0.8 ). Conclusions. Ozone therapy shows positive effect on clinical parameters and skin temperature as measured with thermography. The study indicated possibility of introducing ozonotherapy as an independent therapy in cases with low level of progression or during remission periods and as additional treatment in patients with advanced disease requiring immunosuppressive treatment. Thermography is useful in assessment of skin condition showing strong correlation between skin temperature and clinical parameters.
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The significance of ozone therapy has been increasingly realised in recent times particularly in equine medicine. The beneficial effects of ozone therapy are basically engendered by the mild oxidative stress it creates upon interacting with the extra-cellular and intracellular components. However therapeutic benefits of treatment could be obtained only when it is used within the therapeutic window. Higher doses may be counterproductive and lower doses ineffective. It is now well proved that it up regulates the antioxidant system of the patient and may provide relief from many chronic degenerative diseases upon prolonged use. Ozone therapy has shown encouraging results in the treatment of wide spectrum of diseases and disorders in equines including bacterial and viral infections. Obvious benefits of ozone therapy have been reported in Equine infectious anemia, chlamydial abortions, lymphomas and equine ehrlichiosis. This article provides an insight into the mechanism of action involved in ozone therapy and reviews various conditions which could be treated with the use of ozone therapy in equines.
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This review aims to focus attention on the bio-oxidative therapy from the very beginning to date. While ultraviolet blood irradiation is now hardly performed, oxygen-ozone therapy, after an empirical stage, has grown to be precise and safe. Meantime, there is a renewed interest in the infusion of a dilute solution of hydrogen peroxide in infectious diseases antibiotic-resistant. On a parallel line of research, hyperbaric oxygen therapy has been already accepted by official medicine for the treatment of specific diseases. Meantime it is unfortunate that, owing to quacks’ interest in using ozonated physiologic saline and in claiming to “cure” type-2 diabetes in 20 days with the unprecise rectal ozone administration, ozone therapy is losing hope to be acknowledged as a valid therapeutic approach. [J Exp Integr Med 2011; 1(1): 5-11]
In the last ten years the treatment of lumbar disk herniation is significantly diversified. Other pathologies of the posterior vertebral compartment, as facet joint arthritis and spinal canal stenosis can complicate clinical symptoms. Because of this complex clinical syndrome the ozonetherapy found many applications for its poor invasivity and low cost. Our clinical series of 96 patients, homogeneous for lumbar disk pathologies, age and sex, was divided in two treatment groups: GROUP A treated with 12 injections of O2-O3 gaseous mixture in paravertebral muscles, GROUP B treated with 12 injections of only medical oxygen. A reduction of subjective and objective parameters was observed in both groups. Excellent or good and fair results were observed in 86% of patients. On the other hand from our study arises a statistical evidence of a difference in evolution (time and intensity) of same clinical parameters between the two treated groups.
This paper describes the author's experience of treating acute and chronic disease of the large joints (knee, shoulder, hip) by intra and peri-articular injections of microdoses of an oxygen-ozone gas mixture. Three illustrative case reports are given. The patients were assessed before and after treatment. In addition to a resolution of joint pain, patients had a good functional recovery of their daily activities and the treatment was well-tolerated.
Osteoarthritis of the hip is a chronic invalidating degenerative disease with high social and healthcare costs. Our study aimed to assess the therapeutic efficacy of intra-articular injection of a combination of oxygen-ozone and hyaluronic acid to treat osteoarthritis of the hip joint. Between May 2007 and January 2008, ten patients with clinical and radiological evidence of osteoarthritis of the hip were treated by intra-articular injection of a combination of oxygen ozone gas mixture and hyaluronic acid (HYALUBRIX). One month after the end,of treatment all patients had a 30% recovery of function in the hip joint treated All patients referred major pain relief reaching almost zero on the VAS scale after intra-articular injection of oxygen-ozone and hybluronic acid. Although our series is small, the preliminary findings are encouraging. Intra-articular injection of a combination of oxygen-ozone and hyaluronic acid in the "HYALUBRIX" solution yielded prompt relief ofpain and clinical symptoms in the patients treated, thereby delaying or avoiding recourse to hip replacement surgery.