1. 2022;25;E43-E54Treatment of Femoral Head Osteonecrosis with Ozone Therapy: Pilot Trial of a New Therapeutic Approach
   Nonrandomized Clinical Trial
   Jian-Xiong An, MD, PhD, Guo-Ping Wu, MD, Kun Niu, MD, You-Ping Wei, MD, Hui Liu, MD, Xin-You Gao, MD, Jian-Ping Wu, MD, Yong Wang, MD, Harald Renz, MD, and John P. Williams, MD.

BACKGROUND: Osteonecrosis of the femoral head (ONFH) is a progressive and painful disorder due to impaired blood supply to the femoral head, yet little is known about the effect of ozone therapy in femoral head necrosis.

OBJECTIVES: We aimed to evaluate the clinical and radiographic outcomes of ozone therapy in the treatment of ONFH.

STUDY DESIGN: Nonrandomized clinical trial.

SETTINGS: The study was conducted in a single-center, academic institution.

METHODS: A total of 71 patients (107 hip joints) with Association Research Circulation Osseous (ARCO) stage-I, II, III, and IV ONFH were included and assigned to undergo either intraarticular O2-O3 mixture hip injections with ozonated autohemotherapy (ozone therapy group, n = 39, 58 hip joints) or protected weight bearing (control group, n = 32, 49 hip joints). The primary outcomes included the Visual Analog Scale (VAS) for pain intensity and Harris Hip Score (HHS) for hip function. The secondary outcomes included bone marrow edema examination, and conversion to total hip arthroplasty (THA).

RESULTS: Ozone therapy effectively improves VAS for pain intensity and HHS during the follow-up period compared to the control group. Ozone therapy showed a significant resolution of bone marrow edema of the femoral head compared to the control group (P < 0.001). Thirteen of the 49 hips (26.53%) in the control group underwent THA, whereas only 6 hips (10.34%) in the ozone therapy group required THA during a 30-month follow-up (P = 0.041). The cumulative analysis revealed a low rate of conversion to THA in the ozone therapy group (logrank test; P = 0.022).

LIMITATIONS: The study is limited by a single treatment protocol in addition to the lack of a randomized design.

CONCLUSIONS: Ozone therapy was associated with significant pain relief, improvement in hip function, and bone marrow edema resolution that may delay the need for THA in patients affected by ONFH.

Institutional Review Board (IRB) approval number: HK2018-10-28.

Clinical trials registration number: ChiCTR1900023449.

KEY WORDS: Osteonecrosis of the femoral head, ozone therapy, hip injection, pain intensity, hip function, differential expressed genes, gene ontology, transcriptomics