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Osteoradionecrosis (ORN), also known as postradiation osteonecrosis (PRON), is a serious, debilitating and deforming potential complication of radiation therapy for the treatment of cancer of the head and neck. It has been defined as a necrosis or death of the bone of the mandible or maxilla that may occur following radiation therapy for cancer in the oral and perioral region. It is known to occur when bone, in this case the mandible and/or maxilla, are directly in the field of radiation. The reported incidence ranges from 2.6% to 22% but is most commonly considered to be around 10% +/- 5%. Although it usually occurs in the mandible it can occur in the maxilla and it can occur following brachytherapy (radiation implants).
Diagnosis of ORN depends primarily on clinical and radiographic changes in the bone. These signs and symptoms typically include ulceration of the mucosa, loosening of teeth and exposure of a necrotic bone. Rarely is pain significant and is usually only present when exposure of the necrotic bone persists for more than 3 months.
The development of osteoradionecrosis was only recently understood. Robert E. Marx, DDS, reported that it is not a primary bony infection occurring in irradiated bone. Rather, ORN is a deficiency in the internal physiological condition of the bone and in the metabolic process that is created when cellular structures within the radiated bone are damaged. The sequence of developmental osteoradionecrosis is radiation, formation of hypoxic, hypovascular and hypocellular tissue (tissue low on oxygen supply with fewer than normal vessels and overall fewer tissue cells). Finally, tissues can break down and a chronic non-healing wound can develop.
Studies have shown that the mandibular bone in ORN patients (when compared to irradiated but non-osteoradionecrotic bone and to non-radiated bone) suggests that the inferior alveolar artery was obliterated or damaged to the extent that ischemia (low oxygen supply) occurred in the tissues in the area of distribution. Other bony changes in irradiated bone have also been reported.
From these reports it is now known that radiation affects the vascularity of the bone by eliminating or restricting the blood flow through arteries, arterioles and capillaries and reducing the overall cellularity (amount of tissue cells) of the bone (leukocytes, osteoblasts, and hematopoietic tissue). This in turn leads to hypoxic tissue that is susceptible to damage followed by necrotic changes and ultimately osteoradionecrosis. The body has no way to carry nutrients, oxygen, infection fighting cells and replacement tissues to heal the damage. This can be likened in some way to gangrene of radiated bone.
Specific etiology of ORN is generally considered to be from infection and/or trauma to the alveolar bone secondary to dental or oral pathologic conditions. Typically, the concern is that dental caries may progress to the point of infecting the dental pulp and with time turning into a dental abscess which the body cannot appropriately manage. In addition, it can be induced by the extraction of teeth, even in the absence of active infection. The hypocellularity and hypovascularity permit the bacteria and other pathogens to develop without host defenses counteracting them. Periodontal disease has also been shown in this author's experience to lead to ORN.
It is also assumed that non-tooth related oral trauma, such as that from a denture induced ulceration (denture sore), can permit the underlying bone to be exposed and allow infectious agents to colonize that area, leading to an osteomyelitis (infection of the bone). Non-infectious breakdown of alveolar bone, such as in an edentulous mandible without denture irritation, can lead to ORN, again in this author's experience, probably through general systemic weakness such as diabetes, osteoporosis, etc.
Prevention of ORN is primarily through meticulous attention to pre-radiation treatment planning to eliminate oral disease such as caries, abscess and periodontal disease, which would include the patient maintaining excellent oral hygiene following radiation therapy. Additional preventive considerations include pilocarpine prescribed to assist salivary flow to minimize xerostomia, topical fluoride to control dental caries, and possibly the use of artificial salivary supplements.
Since radiation induced xerostomia is a primary causative factor in dental caries and ultimately ORN, maintenance of a moist oral environment is crucial to the prevention of ORN.
A significant challenge to the dentist is the determination, prior to radiation therapy, of what oral or dental condition pre-exists that requires treatment to limit the possibility of ORN following radiation therapy. Historically the extraction of all teeth in the field of radiation was undertaken to prevent dental disease leading to ORN; this alone can be debilitating to the patient, both physically and emotionally, and patients have been known to refuse radiation therapy for significant oral carcinoma when presented with this treatment plan. This situation can lead to early death from a disease state that might otherwise be controllable; therefore, attention needs to be directed to eradication of dental and oral pathology, and potential oral pathology, prior to radiation therapy.
A group of dental clinicians and researchers from the Netherlands and the United States (Buins, Koole and Jolly) have undertaken studies to define treatment planning and decision making prior to radiation therapy. Conclusions from the first parts of this study have shown that there is a general consensus among dentists and dental oncology specialists in Europe, North America and Australia about treatment planning. In short, a patient receiving radiation therapy for head and neck cancer who presents with normally treatable dental disease (if it were in the healthy individual) but who demonstrates poor oral hygiene history requires dental extraction rather than attempts to restore or retain teeth. However, early stages of dental caries and very early periodontal disease can usually be managed successfully.
Use of Hyperbaric Oxygen
As both a prevention and treatment modality, hyperbaric oxygen (HBO) has been found useful. It is used prophylactically prior to dental extractions and prior to reconstruction of mandibular defects to improve the circulation in the bone, thereby increasing cellularity and the ability of the bone to heal following the surgical procedure. It has been found that the use of hyperbaric oxygen is a means of revascularizing irradiated tissues and improving fibroblastic cellular density which enhances wound healing.
HBO is also used to treat ORN. A study was done with patients who were diagnosed with ORN following radiation therapy in doses ranging from 60 - 90 Grays (Gy); this dosage is often described as 6,000-9,000 centigrays (cGy), or in older terms, 6,000-9,000 rads (the mean dosage was 69.6 Gy). The onset of ORN was noted to occur immediately following radiation therapy or could be delayed in displaying symptoms up to as long as 128 months following radiation therapy. In this study the mean onset time was 12 or 28 months following radiation therapy depending on which treating facility provided the initial radiation therapy.
HBO has been used in more than one manner. Van Merksteyn used HBO in a multiplace chamber at 3.0 ATM (3 atmospheric pressures or 3 times the pressure of air we breathe at sea level) with the patient wearing a mask of 100% oxygen during each of 90-minute treatments. There were 30 preoperative treatment sessions (or dives) followed by 10 postoperative sessions. Another study placed patients in a chamber at 2.5 ATM of pure oxygen for 90-minute treatments with the individualized sessions based on pre-treatment consultation.
Irradiated head and neck cancer patients needing dental extractions may benefit from HBO. HBO may also be indicated as a therapy prior to reconstruction of the mandible and other facial structures. Treatment would usually consist of 20 "dives" prior to dental extraction or reconstruction, followed by the primary closure or extraction and then 10 postoperative dives. (A "dive" is a term given to the period of time when the hyperbaric chamber is slowly pressurized with air. Once at the correct pressure, the patient would begin breathing 100% oxygen.)
The author has used this approach at The Ohio State University Medical Center, Hyperbaric Medicine Unit. Patients were given 20 dives at 2.4 ATM of pure oxygen for 90 minutes (excluding pressurization and depressurization time) prior to dental extractions, then an additional 10 dives immediately following extraction of teeth, radical alveolectomy and primary closure. Utilizing this approach, the author has treated more than two dozen patients in the last decade, and none have developed ORN.
Osteoradionecrosis is a serious possible sequela of radiation therapy for head and neck carcinoma. Prevention is the most important component of the management of potential ORN. Prevention consists of several options:
1. Extraction of diseased and at-risk teeth prior to radiation therapy. Diseased and at-risk teeth are described as those with caries extending into the pulp chamber, those with periapical lesions, periodontal pockets over 4-5 mm, furcation involvements of Grade 2 (mild to moderate mineralized plaque and bacteria and gingivitis on multiple teeth) and mobility of Grade 2 or more. Extractions should be performed a minimum of 2 weeks prior to the beginning of radiation therapy. Teeth that should be treated are those within a field of radiation expected to exceed 50 Gy.
2. Prescription of pilocarpine for the treatment of xerostomia at a dose and schedule of 5 mg three times daily (up to 30 mg total daily dose) beginning one hour prior to the first radiation dose and continuing potentially life-long. Some evidence suggests that beginning pilocarpine prior to radiation therapy could lessen the need for the medication following radiation therapy.
3. Topical fluoride should be provided in a brush-on gel or in a custom tray and used twice daily for 15 minutes. The fluoride can be either a 0.4% stannous fluoride or 1% neutral sodium fluoride preparation.
4. Strict adherence to regular toothbrushing three times daily and flossing daily is of the utmost importance.
5. Edentulous patients should be closely monitored for dehiscence or tissue breakdown of the mucosa under a denture. Denture ulcerations should be treated by leaving the denture out of the mouth until mucosal coverage is complete. Denture soft tissue adjustments and occlusion must be carefully monitored to minimize trauma. Following extractions and radiation therapy denture fabrication should be deferred up to a year or more depending on alveolar healing and overall oral and systemic health.
6. Saliva substitutes can be used to relieve xerostomia. The subjective reports of some patients suggest that water has as much beneficial effect and is less costly than commercial products.
Osteoradionecrosis (ORN) is a potentially debilitating complication of radiation therapy in the treatment of carcinoma in and around the oral cavity. Treatment of ORN is by surgical resection of all necrotic tissue and primary closure of the mucosa. This is supplemented with HBO given in 90-minute sessions at approximately 2.5 ATM of pure oxygen for 20 sessions prior to surgical intervention and followed by 10 additional postoperative dives. Antibiotics, such as penicillins or similar spectrum antibiotics, may be utilized preoperatively and for approximately one week postoperatively.
More research is needed for patients receiving oral bisphosphonate for the treatment of osteoporosis. At this time, it does not seem to be a serious risk and normal dental services are recommended. You should be familiar with the different types of oral bisphosphonates. Any patient who is taking an oral bisphosphonate should be questioned about dosage and reason for usage. A consultation with the patient's physician is always in order.
Brachytherapy - radiation implants or internal radiation.
Carcinoma - an invasive malignant tumor derived from epithelial tissue of the skin or lining of the internal organ that tends to metastasize to other areas of the body.
Cellularity - amount of tissue cells.
Chronic - persisting for a long period of time or marked by frequent recurrences as certain diseases.
Dehiscence - a rupture or splitting open as of a surgical wound.
Dive - is a term given to the period of time when the Hyperbaric Chamber is slowly pressurized with air.
Etiology - the study of causes or origins.
Gangrene - death of tissue, usually due to deficiency in blood flow.
Hematopoietic - stimulates the production of blood cells.
Hypocellular - fewer tissue cells.
Hypovascular - fewer than normal vessels.
Hypoxic - deficiency in the amount of oxygen reaching body tissues.
Ischemia - low oxygen supply.
Leukocytes - white blood cells.
Necrotic - death of cells or tissue through injury or disease, especially in a localized area of the body.
Osteoblasts - a cell from which bone develops, a bone forming cell.
Osteomyelitis - infection of the bone and bone marrow in which the resulting inflammation can lead to a reduction of blood supply to the bone.
Pathogenesis - the development of a disease.
Ulceration - denture sore (could be derived from dentures).
Xerostomia - abnormal dryness of the mouth.
About the Author
Daniel E. Jolly, DDS, FAAHD, FACD, DABSCD
Daniel E. Jolly is in private practice in Columbus, Ohio. He is retired as Professor and Director of the General Practice Residency program at The Ohio State University College of Dentistry and University Medical Center. He has actively practiced dental care for people with cancer for over 30 years and educated the dental team over those same three decades. Dr. Jolly is a Fellow in the American Association of Hospital Dentists and the American College of Dentists. He also is a Diplomate of the American Board of Special Care Dentistry and has served as President of the American Association of Hospital Dentists and the Special Care Dentistry Association.
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