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Dental Ozone Protocol: Medication-Related Osteonecrosis of the Jaw (MRONJ)
Settings published reports used for gas in medication-related osteonecrosis of the jaw. Treatment reports are uncontrolled; the one prevention RCT measured wound healing, with no difference at 6 weeks.
Quick answer: Reports used a sealed tray for 10 minutes per session, with 10 or more sessions per lesion (range 4–38). Treatment reports are uncontrolled. The one prevention trial found healing better at 14 days and the same at 6 weeks.
Warning
Requires training in ozone dentistry
Dental ozone should only be performed by a dental professional trained in ozone dentistry. Gas applied in the mouth carries a higher risk of breathing ozone, which is why devices seal over the tooth and use suction (vacuum) to pull the gas away. Never let the patient inhale ozone gas.
This sheet summarizes what published human studies used. It is not a self-treatment guide and not medical advice. Settings are printed as each study reported them, by device family, and cannot be compared across devices.
What are the basics of ozone for MRONJ?
- Reports of treating established osteonecrosis with ozone are uncontrolled case reports and series. One series of 24 patients reported a 75% response (100% in the 18 who finished the course; 6 stopped because their cancer progressed) with a custom sealed tray alongside surgery in many cases.
- For prevention, one randomized trial of 117 people measured wound healing after extraction in at-risk patients, not MRONJ cases. The total healing score at 6 weeks did not differ; scores at 3–5 and 14 days were better with ozone.
- Madrid (Addendum A, section 11) says osteonecrosis care should be a team effort between dentist and physician, and that systemic ozone given by a physician is also recommended. Before surgery in patients on bisphosphonates, Madrid says ozone conditioning (parenteral ozone about 7–10 days before) may help lower the risk.
- Osteonecrosis is a specialist condition. Sessions were repeated many times, often alongside surgery and standard care.
Uncontrolled evidence for treatment; prevention was tested only on wound healing.
What dose and settings are used for ozone for MRONJ?
One row per use. Settings are exactly as the studies printed them; "not stated" means the paper did not give it.
| Device family | Setting as printed | Time and schedule | |
|---|---|---|---|
| MRONJ treatment (sealed tray) | Medical generator with a custom sealed tray (silicone, inlet and outlet valves) | Series (J Bone Oncol 2012): printed as 20 ppm ±1. Case report (Cicconetti 2016): 20 µg/mL. These are not the same strength, and the series' unit may be an error in the paper (uncertain), so treat the number with care. | 10 min per session, every third day, at least 10 per lesion (range 4–38); stopped when the dead bone came out or surgery was done |
| MRONJ treatment (plasma probe) | Plasma probe | Level 5 | 10 min, 3 times a week for 12 sessions |
| MRONJ treatment (tip generator cycles) | High-frequency tip generator | Power level not stated | Cycles of about 3 min, twice a week, mean 4 cycles |
| Osteoradionecrosis | Tip device (type not stated here) | Not stated | 40 s, 4 sessions (case report) |
| MRONJ risk after extraction (healing outcome) | Not stated | 15 mL gas injected around the socket with a 26G needle, plus insufflation of the socket for at least 1 min; 10 mL injected again at 3–5 days, 14 days and 6 weeks | 4 visits (outcome was a wound-healing score, not MRONJ cases) |
Madrid's dental addendum: Madrid (section 11) gives no gas settings for osteonecrosis. It describes ozone as a complement to standard care, with ozone injections around the lesion and into the necrotic bone (kept moist), and says systemic ozone given by a physician is also recommended. Device settings in the table (ppm, power level, seconds) are not directly comparable to Madrid's µg/mL values.
What are the best tips when using ozone for MRONJ?
- The custom tray is silicone with inlet and outlet valves, so gas can flow in and out of the tray.
- In the series with the best reported response, ozone was often combined with surgery.
- Settings are device-specific (ppm, power level, seconds). Use your own device's program and do not convert one family's setting into another's.
- Most single-tooth uses were one application. Where the studies gave a schedule, it is in the table.
What are the precautions for ozone for MRONJ, and who should avoid it?
- Device families used in this sheet (generic descriptions). Sealed-cup (vacuum) device: a silicone cup seals over the tooth and holds a vacuum. Probe-tip device: a handpiece with a tip, usually a fixed concentration or a power level. High-frequency tip generator: ozone is made at the tip and set by power percent. Timed-burst handpiece: a preset dose set by seconds. Medical generator: a standard medical ozone generator giving a dose in µg/mL, with a syringe or custom sealed tray.
- Use high-volume suction or an ozone destruct unit at the mouth, and ventilate the room.
- Screen the patient first. Review pregnancy, heart or bleeding conditions and blood thinners with the patient's physician before gas is used.
- The Madrid Declaration on Ozone Therapy, 4th edition (ISCO3, 2025) dentistry addendum (Addendum A, section 2.1) sets the safety rules for gas in the mouth: stop at the first smell of ozone and check for leaks; use the dental unit's high-volume suction even when the handpiece has its own suction line; seal custom trays at every edge and test the seal before use; and keep 1 g of vitamin C and medical oxygen with a mask (3 L/min) in the office in case the patient breathes in ozone. For cup or tray gas on tooth surfaces (section 4.1), Madrid lists as contraindications: a tooth or mouth shape that stops a full seal, no high-volume suction, and a tooth with an apical lesion (endodontic treatment or extraction fits better). The full contraindication list in section 2.1 of the main text is written for ozone given through the body. How MediSkill handles contraindications is explained in the contraindications article.
- Use medical oxygen to make the gas. Madrid says generators that run on room air also make harmful nitrogen compounds, and industrial oxygen must not be used. Many of the dental studies here used such devices, so their settings may not match a medical-oxygen generator. Madrid's dentistry addendum allows an oxygen concentrator of 95% or higher purity for topical dental use and calls for medical-grade oxygen (99.9%) for any injection. MediSkill's rule is medical oxygen.
- Check your licensing board and that your device is cleared for dental use where you practice.
More detail
Equipment
- Medical ozone generator with a custom silicone tray with inlet and outlet valves, or a plasma probe
- Ozone destruct unit on the outlet
- Standard care and surgical set-up for MRONJ
What the studies used
Study doses are listed as printed in each paper. They are not Madrid dosing; see the Madrid line under the dosing table. "RCT" means randomized controlled trial (people were assigned to groups by chance).
- Sealed tray, 10 min, at least 10 sessions per lesion: case series of 24, 75% response, printed as 20 ppm (J Bone Oncol 2012); case report at 20 µg/mL (Cicconetti 2016).
- Plasma probe level 5, 10 min, 3 times a week for 12: case series of 2 (Kaptan 2013). Tip-generator cycles of about 3 min (mean 4): case series of 94 (Eur Rev Med Pharmacol Sci 2012).
- Osteoradionecrosis, 40 s for 4 sessions: case report (Saudi Med J 2014).
- Prevention: RCT of 117 measured wound healing, not MRONJ cases. Total healing score at 6 weeks did not differ; scores at 3–5 and 14 days were better with ozone (Oral Dis 2024).
Evidence is thin: uncontrolled case reports and series for treatment, and the only RCT measured wound healing after extraction, not MRONJ cases.
Learn more
Background, benefits and research on dental ozone: Ozone in dentistry, full article.
Related protocols: Dental Ozone Protocol: Tooth Decay and Sensitivity, Dental Ozone Protocol: Gum Disease, Peri-Implantitis and Implant Stability, Dental Ozone Protocol: Oral Surgery and Healing.
Other dental protocols
For licensed practitioners. Educational reference only, not medical advice. Follow your scope of practice and local regulations.