Effects of hyperbaric oxygen therapy on human musculoskeletal pathologies in clinical studies: a systematic review

Abstract

Abstract Background Hyperbaric oxygen therapy (HBOT) has gained increasing interest in regenerative medicine for its capacity to enhance tissue oxygenation, reduce inflammation, and accelerate healing. While its use in musculoskeletal medicine is expanding, particularly among athletes and in sports orthopaedics, the clinical evidence base remains fragmented across indications and has not been systematically evaluated. Purpose The aim of this systematic review was to synthesize the available clinical evidence for HBOT in human musculoskeletal pathologies, with focus on its application in orthopaedic medicine. Methods A systematic PubMed and LIVIVO search identified clinical studies (January 1996 - January 2026) investigating intervention-based studies using HBOT for musculoskeletal conditions in humans. Exclusion criteria were combinatory therapies, transplantations, radiation injuries, osteomyelitis, spine and oral surgery. Data on study design, HBOT protocols and their outcomes was collected. A qualitative synthesis was performed due to heterogeneity in study designs and outcome measures. Risk of bias was assessed using Cochrane RoB 2 tool (RCTs) and ROBINS-I V2 (non-RCTs). Studies were categorized by pathology (muscle/tendons/ligament injury; avascular necrosis (AVN) and bone marrow edema (BME)). Results Nineteen studies involving 612 patients met our inclusion criteria. Conditions included exercise-induced muscle damage (EIMD) and its symptomatic manifestation delayed onset muscle soreness (DOMS), ligament injuries, AVN, BME, and tendon perfusion. Evidence for HBOT’s effects in DOMS/EIMD was limited, with RCTs showing no significant benefit. Conversely, AVN and BME studies reported consistent improvements in imaging, pain and functional scores, particularly with prolonged protocols. Limited evidence suggested potential benefits in ligament healing; tendon oxygenation effects were inconclusive. HBOT protocols ranged from 1 - 12 sessions for soft-tissue and 20 - 80 sessions for bone injuries, mainly using 60 to 90 minute sessions with 100% oxygen. Adverse events were rare and mild. Most RCTs showed low risk of bias; non-randomized studies had serious-to-critical bias due to confounding and measurement issues. Conclusions HBOT may have a role as an adjunctive therapy for musculoskeletal pathologies, especially AVN and BME, where the most consistent evidence was observed, while its benefit in ligament injuries, muscle recovery, and tendon pathology remains inconclusive and requires higher-quality trials to substantiate. Clinical relevance This topic is directly relevant to orthopaedic and sports medicine practitioners considering its off-label use. This review identifies conditions with the most consistent clinical benefit, highlights the limitations of current evidence, and defines priorities for future high-quality trials to guide safe and effective clinical implementation. Study design Systematic review.