Original Title: Hyperbar oksygenbehandling av osteonekrose

Authors' objectives: Hyperbaric oxygen treatment (HBOT) has been suggested as an alternative or adjunct treatment that can prevent further development of osteonecrosis, a bone disease in which bone structure deteriorates. Patients receiving HBOT breathe pure oxygen in a high-pressure chamber. We have summarized research on the clinical effect and safety of HBOT as a treatment for osteonecrosis. We have also examined the cost-effectiveness and budget consequences of HBOT.

Authors' results and conclusions: Effectiveness and safety: We included two systematic reviews, two RCTs and 13 case series in this health technology assessment. We considered the methodological quality of the systematic reviews as high. The risk of bias we considered unclear in one RCT and high in the other. Because case series are generally considered a poor research design, we did undertake our own quality assessment of this evidence. One systematic review included three RCTs on effects of HBOT of radiation-related osteonecrosis in the jaw. More patients receiving HBOT achieved complete mucosal coverage at 12- to 18 months’ follow-up, than in control groups (RR 1.30; 95% CI 1.09 - 1.55; 3 studies / 246 participants). We had medium confidence in the effect estimate. The effect estimate of the absence of osteonecrosis after one year was RR 0.60 with 95% CI 0.25 to 1.41 (1 study). Our confidence in the effect rate was very low. The other systematic review included one RCT that examined the effect of HBOT for drug-related osteoarthritis on healing, compared to standard treatment. The effect estimate was RR 1.56 with 95% CI 0.77 to 3.18 (1 study). Our confidence in the effect estimate was very low. The two RCTs examined the effect of HBOT for osteonecrosis in the hip joint, but there was only one that reported data from which effect estimates could be calculated. The RCT compared a "cocktail treatment" that included HBO with shockwave treatment. The outcomes were joint survival (RR 1.00; 95% CI 0.88 to 1.15), radiological findings (RR 0.96; 95% CI 0.30 to 3.11), pain (MD 0.4; 95% CI -0.16 to 0.96) and quality of life (MD -3.35; 95% CI -6.14 to -0.56 and MD -2.03; 95% CI -4.30 to 0.24 for physical and mental health, respectively). Our confidence in all effect estimates was very low. Results from 13 case studies and three RCTs (one of which was derived from a systematic review) indicated few or no complications or adverse effects from HBOT. Health economics: The cost per additional patient who achieves complete mucosal coverage of the jawbone is approximately NOK 341 000 for patients treated with HBO in addition to standard treatment compared to patients receiving only standard treatment. Probabilistic sensitivity analysis shows that the cost per additional complete mucosal coverage may vary from approximately NOK 268,500 to NOK 491,000. When the proportion of patients requiring extensive surgical reconstruction of the jaw is varied from 5% to 85%, the cost per extra full mucosal coverage ranges from approximately NOK 382 500 to NOK 50 570. Budgetary implications for treatment of 17 patients per year are estimated at additional costs of approximately NOK 6 202 400 (4% discount rate). Cost per additional patient who achieves complete mucous membrane coverage is approx. NOK 341 000 among patients treated with HBO in addition to standard treatment compared to patients receiving standard treatment. Probabilistic sensitivity analysis shows that the cost per additional complete mucosal coverage may vary from approximately NOK 268,500 to NOK 491,000. When the proportion of patients requiring extensive surgical reconstruction of the jaw is varied from 5% to 85%, the cost per extra full mucous membrane coverage ranges from approx. NOK 382 500 to NOK 50 570. Budgetary implications for treatment of approximately 17 patients per year are estimated at additional costs of approx. NOK 6 202 400 (4% discount rate). It was not possible to create a cost-effectiveness model of HBOT for either drug-related osteonecrosis of the jaw (ORNJ) or osteonecrosis of the hip. Five-year discounted costs for treatment of 50 ORNJ patients are approximately NOK 16,400 213. Treatment of 200 patients per year with osteonecrosis of the hip may cost NOK 18,446,000 discounted over five years. In both cases, it was not possible to calculate additional costs in relation to standard treatment. Conclusion: HBOT for radiation-related osteonecrosis can lead to more patients achieving complete mucosal coverage of the jawbone than with standard treatment. For these patients HBOT could potentially be interpreted as cost effective if the willingness-to-pay for an additional patient who achieves complete mucosal coverage of the jaw is more than approximately NOK 341 000. The evidence is too uncertain to answer the question of the efficacy and safety of HBOT for other outcomes, and in the case of other types of osteonecrosis. Thus, we do not know whether HBOT in addition to standard treatment gives better, poorer or identical effects on any of the outcomes, compared to other or no treatment. In order to provide better research-based answers to questions about the effect of HBOT, future studies should be based on a controlled, prospective study design; and include relevant clinical outcomes, study populations of adequate size, and opportunities for long-term follow-up. Children should also be included in the studies.

Authors' methods: Effectiveness and safety: We searched for systematic overviews and primary studies in the following databases in March / April 2018: Cochrane Library, MEDLINE, PubMed, Embase, CEA Registry and Epistemonikos databases, Center for Reviews and Disseminations. In addition, we searched for studies on the websites of international publishers of guidelines, and in registers for controlled studies. Two researchers made paired and independent assessments of the eligibility of the studies according to pre-specified inclusion and exclusion criteria, and methodological quality (risk of systematic bias) in included studies. We extracted data from all relevant studies and presented them in text and tables. We assessed our confidence in effect estimates using Grading of Recommendations, Assessment, Development and Evaluation (GRADE). Health economics: We developed a simple decision-tree model to assess cost-effectiveness of HBOT in addition to standard treatment compared to standard treatment alone for osteoradionecrosis of the jaw. The model’s outcome was an incremental cost-effectiveness ratio (ICER) where cost was measured in 2018 Norwegian kroner and effect was measured as the proportion of patients achieving complete mucosal coverage of the jawbone. We assumed no relapse among patients who achieved complete mucosal coverage. Patients who do not achieve full mucosal coverage receive surgical treatment. We assumed that 15% will require extensive surgical reconstruction of the jaw, while 85% require less extensive surgery. To take into account uncertainty, we ran a one-way sensitivity analysis on the effect of varying the proportion of patients who need surgical reconstruction. We used probabilistic sensitivity analysis to see the impact of uncertainty in effect estimate on results. We calculated budget impacts over five years.

Project Status: Completed

Year Published: 2019

URL for published report: https://www.fhi.no/en/publ/2019/Hyperbaric-oxygen-therapy-for-osteonecrosis/

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: Norway

Organisation Name: Norwegian Institute of Public Health

Contact Address: P.O. Box 222 Skoyen, N-0123, Oslo