Literature

Literature

The following is a selection of peer-reviewed papers describing the experience with ozone applied to the spine. This listing is representative of the literature but Minimus Spine does not represent that this listing is complete. The reader is encouraged to do their own research.

These papers did not utilize Minimus Spine’s Triojection® System. Minimus developed Triojection to improve sterilization assurance and give confidence in a consistent procedure.


Clinical Studies


Zhang Y, Ma Y, Jiang J, Ding T, Wang J. Treatment of the lumbar disc herniation with intradiscal and intraforaminal injection of oxygen-ozone. J Back Musculoskelet Rehabil. 2013;26(3):317-22.

Brief Description…
A blinded randomized trial of 172 patients with back and leg pain associated with a herniated disc. Patients were randomized to receive ozone alone or ozone in combination with steroids. Patients were blinded to their treatment and followed for 12 months. Patients in both groups improved significantly. The addition of steroids did not result in a significantly better outcome relative to ozone alone. Read More…


Gallucci M, Limbucci N, Zugaro L, Barile A, Stavroulis E, Ricci A, Galzio R, Masiocchi C. Sciatica: Treatment with intradiscal and intraformainal injections of steroid and oxygen-ozone versus steroid only. Radiology 2007; 242: 907-913.

Brief Description…
A blinded randomized trial of 159 patients receiving either steroids or steroid in combination with intradiscal ozone. Patients were followed for 6 months. Those treated with ozone had significantly better results than those treated with just steroids. Read More…


Lehnert T, Naguib NN, Wutzler S, Nour-Eldin NE, Bauer RW, Kerl JM, Vogl TJ, Balzer JO.  Analysis of disc volume before and after CT-guided intradiscal and periganglionic ozone-oxygen injection for the treatment of lumbar disc herniation.  J Vasc Interv Radiol 2012; 23(11):1430-36.

Brief Description…
A blinded radiological review of disc volume in 283 patients before and six months after intradiscal injection of ozone into a herniated disc.  On average, disc volume decreased by 7% and 96% of patients demonstrated some amount of decrease in volume.  Four percent increased.  Discs that started off larger tended to shrink more.  Younger discs tended to shrink more.  These observations are consistent with previously clinical reports. Read More…


Buric J, Molino Lova R. Ozone chemonucleolysis in non-contained lumbar disc herniations: a pilot study with 12 months follow-up. Acta Neurochir Suppl. 2005;92:93-7.

Brief Description…
A study of 30 patients with non-contained disc herniation that were treated with intradiscal ozone injection and followed for one year. Ninety percent of patients reported significant improvements in pain and function. Read More…


Muto M, Andreula C, Leonardi M. Treatment of herniated lumbar disc by intradiscal and intraforaminal oxygen-ozone (O2-O3) injection. J Neuroradiol. 2004 Jun;31(3):183-9.

Brief Description…
Authors report their experience in treating 2,200 patients with various spine pathologies with spinal injections of ozone. Treatment found to be most effective for disc herniation, followed by degenerative disc disease. Patients with stenosis or failed back syndrome had little benefit.Read More…


Paradiso R, Alexandre A. The different outcomes of patients with disc herniation treated either by microdiscectomy, or by intradiscal ozone injection. Acta Neurochir Suppl. 2005;92:139-42.

Brief Description…
Authors retrospectively identified two demographically matched groups, each containing 150 patients, treated with either surgical discectomy or intradiscal ozone injection. The investigators concluded that both groups demonstrated significant improvements and stated that surgical discectomy is preferred in cases with migrated fragments whereas ozone is preferred in cases without migrated fragments. Read More…


Pauloni M, DiSante L, Cacchio A, Apuzzo D, Marotta S, Razzano M, Franzini M, Santilli V. Intramuscular oxygen-ozone therapy in the treatment of acute back pain with lumbar disc herniation. A multicenter, randomized, double blind, clinical trial of active and simulated lumbar paravertebral injection. Spine 2009; 34(13): 1337-1344.

Brief Description…
A randomized, double blinded trial of 60 patients receiving a series of either paravertebral injections of ozone or a sham injection. Patients were followed for 6 months. Patients receiving ozone had significantly lower pain scores throughout follow-up and almost twice as many were pain free at six months. This study did not involve intradiscal injections. Read More…


Individual Case Reports of Complications


Fort NM, Aichmair A, Miller AO, Girardi FP. L5-S1 Achromobacter xylosoxidans infection secondary to oxygen-ozone therapy for the treatment of lumbosacral disc herniation: a case report and review of the literature. Spine 2014; 15;39(6):E413-6.

Brief Description…
A case report of a disc infection following ozone injection into L5-S1. Patient was surgically fused using hardware and treated with antibiotics. This resolved symptoms. Intraoperative cultures grew A. xylosoxidans and Propionibacterium acnes. Authors called attention to the wide variety of environmental pathogens that can complicate percutaneous procedures. Read More…


Bo W, Longyi C, Jian T, Guangfu H, Hailong F, Weidong L, Haibin T. A pyogenic discitis at C3-C4 with associated ventral epidural abscess involving C1-C4 after intradiscal oxygen-ozone chemonucleolysis. A case report. Spine 2009; 34(8): E298-E304.

Brief Description…
A case report of an infection by S. Bovis following an ozone injection in the cervical spine. Authors highlight the need to pay attention to sterility during these procedures. Read More…


Gazzeri R, Galarza M, Neroni M, Esposito S, Alfieri A. Fulminating septicemia secondary to oxygen-ozone therapy in lumbar disc herniation. Case report. Spine 2007; 12(3): E121-E123.

Brief Description…
A case report of an infection of E. Coli following an ozone injection, highlighting the importance of sterility during these procedures. Read More…


Lo Guidice G, Valdi F, Gismondi M, Prosdocimo G, de Belvis V. Oxygen-ozone therapy for lumbar disk herniation. Am J Ophthalmology 2004: 138(1): 175-177.

Brief Description…
A case report of a patient receiving an unusually large a volume of gas resulting in temporary loss of vision when the gas migrated up the spinal canal. This case highlights the need for a controlled, limited volume of gas. Read More...


Animal Studies


Murphy K, Elias G, Steppan J, Boxley C, Balagurunathan K, Victor X, Meaders T, Muto M. Percutaneous Treatment of Herniated Lumbar Discs with Ozone: Investigation of the Mechanisms of Action. J Vasc Interv Radiol. 2016 Aug;27(8):1242-1250.

Brief Description…
An animal study reporting the fragmentation of GAG molecules in the disc nucleus following ozone exposure, resulting in a reduction in disc volume. Also, reported changes in cytokine expression following ozone injection. Read More…


Tian JL, Zhang JS, Xiao YY, Liu JT, Yang B, Li JK, Yu M. Changes of CSF and spinal pathomorphology after high-concentration ozone injection into the subarachnoid space: an experimental study in pigs. Am J Neuroradiol 2007; 28: 1051-54.

Brief Description…
An animal study injecting high concentrations of ozone into the spinal canal of pigs. The authors reported no signs of toxicity or neurological injury. Read More…


Chen H, Yu B, Lu C, Lin Q. The effect of intra-articular injection of different concentrations of ozone on the level of TNF-alpha, TNF-R1, and TNF-R2 in rats with rheumatoid arthritis. Rheumatol Int October 2012: Epub ahead of print.

Brief Description…
An animal study evaluating the effects of ozone on inflammation and cytokine expression. Forty-eight rats with induced rheumatoid arthritis were divided into eight groups, receiving 0, 10, 20… 50mcg/cc ozone in oxygen and untreated controls. Rats were given an intra-articular injection weekly for three weeks. Animals receiving injection of 40 mcg/cc showed had less thickness in the affected paw and there were lower levels of TNF-alpha and TNF-R2 in the groups receiving 40 and 50 mcg/cc. Read More…


Fuccio C et al. A single subcutaneous injection of ozone prevents allodynia and decreases the over-expression of pro-inflammatory caspases in the orbito-frontal corex of neuropathic mice. Eur J Pharmacol 2009; 601(1-3): 42-49.

Brief Description…
An animal study whereby a nerve root injury was created and then followed with a single subcutaneous injection of ozone. Authors reported that ozone was responsible for decreases in inflammatory mediators in the brain and improvements in expressed pain. Read More…


Chang JDS, Lu HS, Chang YF, Wang D. Ameliorative effect on ozone on cytokine production in mice injected with human rheumatoid arthritis synovial fibroblast cells. Rheumatol Int 2005:26:141-151.

Brief Description…
An animal study evaluating the effect of ozone at various concentrations and nitrogen (serving as a control) on inflammatory cytokines expressed by cultured fibroblasts. Treatment with ozone 3% and 5% reduced the expression of inflammatory cytokines without toxicity or serious side effects. Read More…