Platelet-Rich Fibrin for Preventing Osteoradionecrosis After Dental Extractions

This is a multicentre, randomized controlled trial evaluating platelet-rich fibrin (PRF) for the prevention of osteoradionecrosis (ORN) following dental extraction in adults who have previously received radiation therapy involving the jaws.

Eligible participants requiring extraction of one or more teeth within a previously irradiated field will be randomized in a 1:1 ratio to receive either PRF plus standard extraction care or standard extraction care alone.

For participants allocated to the intervention group, autologous PRF will be prepared chairside from venous blood using horizontal centrifugation and placed into the extraction socket(s) during the same procedure. The PRF will not be stored or transported.

The study will evaluate whether adjunctive PRF reduces the occurrence of ORN following dental extraction and will also evaluate clinical soft-tissue healing, radiographic bone healing, postoperative pain, analgesic use, postoperative complications, and adverse events.

The study will be conducted at participating centres in Winnipeg, Manitoba, and Calgary, Alberta, Canada.

• Platelet-rich fibrin (PRF) (Procedure): Autologous platelet-rich fibrin (PRF) will be prepared chairside from venous blood collected from the participant. Blood will be processed using horizontal centrifugation to produce PRF. The prepared PRF will be placed into the eligible dental extraction socket(s) during the same procedure. PRF will not be stored or transported.
• Standard Dental Extraction Care (Procedure): Participants will undergo extraction of one or more eligible teeth within a previously irradiated area of the jaw using standard dental extraction care. No platelet-rich fibrin (PRF) will be placed in the extraction socket(s) as part of this intervention.

Primary outcomes

• Incidence of Osteoradionecrosis Within 6 Months [From dental extraction through 6 months after extraction]: Osteoradionecrosis (ORN) will be assessed at the participant level using the ClinRad definition adopted by the ISOO-MASCC-ASCO guideline. ORN is defined as a radiographic lytic or mixed sclerotic lesion of bone, visibly exposed bone, and/or bone probeable through a periodontal pocket or fistula within an anatomical site previously exposed to therapeutic head and neck radiation. A participant will meet the primary endpoint if at least one study extraction socket meets the definition at any scheduled or unscheduled visit through 6 months.

Secondary outcomes

• Complete Mucosal Closure of the Extraction Site [2 weeks, 6 weeks, 3 months, and 6 months after dental extraction]: Complete mucosal closure will be assessed clinically at each study extraction socket and recorded as a binary outcome (yes/no). Complete mucosal closure is defined as intact epithelium across the entire socket orifice, with no dehiscence and no exposed bone. Socket-level outcomes will account for clustering of multiple extraction sockets within individual participants.
• Radiographic Bone Healing at the Extraction Site [Baseline to 6 months after dental extraction]: Radiographic bone healing at each study extraction site will be assessed by qualitative comparison of the 6-month cone-beam computed tomography (CBCT) scan with the pre-extraction baseline CBCT. Assessment will include the presence, absence, and extent of lytic or mixed sclerotic changes and cortical continuity at the socket crest.
• Postoperative Pain Intensity [2 weeks, 6 weeks, 3 months, and 6 months after dental extraction]: Pain intensity at each study extraction socket will be assessed using the 11-point Numeric Rating Scale (NRS-11), ranging from 0 to 10, where 0 represents no pain and 10 represents the worst pain imaginable. Participants will rate pain at each extraction site over the preceding 24 hours. Higher scores indicate greater pain intensity.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

Age 18 years or older. History of head and neck cancer treated with radiation therapy. Requires at least one dental extraction within an area of the jaw that was previously treated with radiation.

Willing and able to attend all study follow-up visits. No minimum or maximum time since completion of radiation therapy is required.

Exclusion Criteria:

Abscess or draining sinus tract associated with a planned study extraction site.

Blood disorder affecting platelet production or function, such as thrombocytopenia, hemophilia, von Willebrand disease, or a qualitative platelet disorder.

Current immunosuppressive therapy, including calcineurin inhibitors, antimetabolites, biologic therapy, or active cytotoxic chemotherapy.

Current tobacco use in any form, including nicotine vaping, within the previous 30 days.

Known recurrence of head and neck cancer. Previous re-irradiation or re-irradiation currently planned. Chronic systemic corticosteroid use equivalent to at least 5 mg of prednisone daily for at least 30 consecutive days within the previous 3 months.

Current or previous bisphosphonate therapy by any route. Denosumab within the previous 12 months or use of another antiresorptive or antiangiogenic medication.

Current pregnancy. Therapeutic low-molecular-weight heparin or unfractionated heparin that cannot be scheduled at trough level.

• Julia M Burgess, DMD (current OMFS Resident), Principal investigator, University of Manitoba
• Reda Elgazzar, Oral and Maxillofacial Surgeon, Study director, University of Manitoba
• Edmund Chan, DMD, Study director, University of Calgary