Oxygen-Ozone Therapy in the Rehabilitation Field: State of the Art on Mechanisms of Action, Safety and Effectiveness in Patients with Musculoskeletal Disorders

Biomolecules. 2021 Feb 26;11(3):356. doi: 10.3390/biom11030356.


In recent years, the interest in oxygen-ozone (O2O3) therapy application has considerably increased in the field of rehabilitation. Despite its widespread use in common clinical practice, the biochemical effects of O2O3 are still far from being understood, although its chemical properties seem to play a pivotal role in exerting its positive effects on different pathological conditions. Indeed, the effectiveness of O2O3 therapy might be partly due to the moderate oxidative stress produced by O3 interactions with biological components. O2O3 therapy is widely used as an adjuvant therapeutic option in several pathological conditions characterized by chronic inflammatory processes and immune over-activation, and most musculoskeletal disorders share these pathophysiological processes. The present comprehensive review depicts the state-of-the-art on the mechanisms of action, safety and effectiveness of O2O3 therapy in the complex scenario of the management of musculoskeletal disorders. Taken together, our findings suggest that O2O3 therapy seems to reduce pain and improve functioning in patients affected by low back pain and knee osteoarthritis, as reported by several studies in the literature. However, to date, further studies are warranted to clearly investigate the therapeutic effects of this promising therapy on other musculoskeletal disorders in the field of rehabilitation.

Keywords: fibromyalgia; low back pain; neck pain; osteoarthritis; oxygen ozone; oxygen–ozone therapy; ozone; pain management; rehabilitation; tendinopathy.

Publication types

  • Review

MeSH terms

  • Animals
  • Fibromyalgia / drug therapy
  • Fibromyalgia / metabolism
  • Humans
  • Low Back Pain / drug therapy
  • Low Back Pain / metabolism
  • Musculoskeletal Diseases / drug therapy*
  • Musculoskeletal Diseases / metabolism*
  • Neck Pain / drug therapy
  • Neck Pain / metabolism
  • Osteoarthritis, Knee / drug therapy*
  • Osteoarthritis, Knee / metabolism*
  • Oxygen / therapeutic use*
  • Ozone / therapeutic use*


  • Ozone
  • Oxygen