Osteoradionecrosis, oral health and dental treatment.

Introduction

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 most commonly considered to be around 10% +/- 5%. Although it usually occurs in the mandible (lower jaw) it can occur in the upper jaw and it can occur following brachytherapy (radiation implants).

Course Objectives

Upon completion of this course, the reader should be able to:

1. Explain what Osteoradionecrosis (ORN) is.

2. Explain the development of Osteoradionecrosis (ORN).

3. Identify the signs and symptoms of Osteoradionecrosis (ORN).

4. Describe how radiation affects the vascularity of the bone.

5. List five measures taken to prevent Osteoradionecrosis (ORN).

6. Explain what role Hyperbaric Oxygen plays as both a prevention and treatment modality.

7. Explain what Hyperbaric Oxygen is and how it benefits patients with Osteoradionecrosis (ORN).

Outline

I. Introduction

II. Course Objectives

III. Outline

IV. Diagnosis

V. Pathogenesis

VI. Prevention

VII. Use of Hyperbaric Oxygen

VIII. Discussion

IX. Summary

X. Test Questions

Diagnosis

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 the teeth, exposure of the necrotic bone; but rarely is pain a significant component of signs and symptoms. It is said to be present when exposure of the necrotic bone persists for more than three months.

Pathogenesis

The development of osteoradionecrosis was only recently understood. Marx reported that it is not a primary bony infection occurring in irradiated bone. Rather, it 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 development of 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 nonhealing wound can develop.

Studies have shown that the mandibular bone in ORN patients, when compared to irradiated but nonosteoradionecrotic bone and to nonradiated 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, hematopoetic 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 a 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 for dental caries to progress to the point of infecting the tooth nerve and later turning into a dental abscess that 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, as well.

It is also assumed that nontooth-related oral trauma, such as that from a denture-induced ulceration (denture sore), can permit the underlying bone to be exposed and infectious agents colonize that area, leading to an osteomyelitis (infection of the bone). Noninfectious 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

Prevention of ORN is primarily through meticulous attention to preradiation treatment planning to eliminate oral disease such as caries, abscess and periodontal disease. Prevention also requires the patient to maintain 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. 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 (Bruins, 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 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 that enhances wound healing.

Hyperbaric oxygen (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 as early as immediately following radiation therapy or could be delayed in displaying symptons up to as long as 128 months following RT. 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 breath 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 pretreatment 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.

Discussion

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 and mobility of Grade 2 or more. Extractions should be performed a minimum of two 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 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.

Summary

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.

GLOSSARY

Brachytherapy--Radiation implants

Carcinoma--An invasive malignant tumor derived from epithelial tissue that tends to metastasize to other areas of the body

Cellularity--Amount of tissue cells

Chronic--Lasting 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--A term given to the period of time when the hyperbaric chamber is slowly pressurized with air

Etiology--The study of causes or origins

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

Xerostomia--Abnormal dryness of the mouth

REFERENCES

Beumer J III, Harrison R, Sanders B, Kurrasch M. Postradiation dental extractions: a review of the literature and a report of 72 episodes. Head Neck Surg 1983; 6:581-6.

Bras J, de Jonge HK. van Merkesteyn JP. Osteoradionecrosis of the mandible: pathogenesis. Am J Otolaryngol 1990; 11: 244-50.

Bruins H, Koole R, Jolly DE. Pretherapy dental decisions in patients with head and neck cancer. Oral Surg Oral Med Oral Pathol Oral Radiol 1998; 86:256-67.

Bruins K, Jolly DE, Koole R. Preradiation dental decisions in patients with head and neck cancer. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999; 88:406-12.

Davis JC, Dun JM, Gates GD, et al. Hyperbaric oxygen: a new adjunct in the management of radiation necrosis. Arch Otolaryngol 1979; 105:58-61.

Epstein J, van der Meij E, McKenzie M, Wong F. Lepawsky M, Stevenson-Moore, P. Postradiation osteonecrosis of the mandible. Oral Surg Oral Med Oral Path 1997; 83(6):657-662.

Epstein JB, Rea G, Wong FL, Spinelli J, Stevenson-Moore 17 Osteonecrosis; study of the relationship of dental extractions in patients receiving radiotherapy. Head Neck Surg.1987; 10:48-54.

Epstein JB, Wong FL, Stevenson-Moore P. Osteoradionecrosis: clinical experience and a proposal for classification. J Oral Maxillofac Surg 1987; 45:104-110

Farmer JC, Shelton DL, Angelillo JD, Ferguson BJ. Treatment of radiation-induced tissue injury by hyperbaric oxygen. Ann Otolaryngol 1987; 87:707-15.

Fattore L, Strauss RA. Hyperbaric oxygen in the treatment of osteoradionecrosis: a review of its use and efficacy. Oral Surg Oral Med Oral Pathol 1987; 63:280-6.

Friedman RB. Osteoradionecrosis: causes and prevention. NCO Monogr 1990: 145-9

Galler C, Epstein JB, Guze KA, Buckles D, Stevenson-Moore P. The development of osteoradionecrosis from sites of periodontal disease activity: report of three cases. J Periodontol 1992; 4:310-6

Kluth EV, Jain PR, Stuchell RN, Frich JC Jr. A study of the factors contributing to the development of osteoradionecrosis of the jaws. J Prosthet Dent 1988; 59:194-201.

Li JH, Peh WC, Sham JS. Maxillary osteonecrosis after radiotherapy for nasopharyngeal carcinoma. Clin Oncol (R Coll Radiol) 1994; 6:135-6.

Lozza L, Cerrotta A, Gardani G, De Marie M, Di Russo A, Kenda R, Tana S, Valvo F, Zucali R. Analysys of the risk factors for mandibular bone radionecrosis after exclusive low dose-rate brachytherapy for oral cancer. Radiother Oncol 1997; 44:143-7.

Mainous EG, Hart GB. Osteoradionecrosis of the mandible: treatment with hyperbaric oxygen. Arch Otolaryngol 1975; 101:173-7.

Mansfield MJ, Sanders DW, Heinbach RD, et al. Hyperbaric oxygen as an adjunct in the treatment of osteoradionecrosis of the mandible. J Oral Surg 1981; 39:585-9.

Marx RE. Osteoradionecrosis: a new concept of its pathophysiology. J Oral Maxillofac Surg 1983; 41:283-7.

Marx, RE. Osteonecrosis of the jaws: a review and update. Hyperbaric Oxygen Rev 1984; 5:78-127.

Marx RE, Ames JR. The use of hyperbaric oxygen in bony reconstruction of the irradiated and tissue deficient patient. J Oral Maxillofac Surg 1982; 40:412-20.

Marx RE, Johnson RP, Kline SN. Prevention of osteoradionecrosis: a randomized prospective clinical trial of hyperbaric oxygen vs. penicillin. J Am Dent Assoc 1985; 111:49-54.

Mitchell HJ, Logan PM. Radiation-induced changes in bone. Radiographics 1998; 18:1125-36.

Murray GC, Daly TE, Zimmerman SO. The relationship between dental disease and radiation necrosis of the mandible. Oral Surg Oral Med Oral Pathol 1980; 49:99-104.

Murray GC, Herson J, Daly TE. Radiation necrosis of the mandible: a 10 year study. Part I--Dental factors: onset, duration, and management factors influencing the onset of necrosis. Int J Radiat Oncol Biol Phys 1980; 6:543-8.

Patel P, Raybould T, Maruyama Y. Osteoradionecrosis of the jaw bones at the University of Kentucky Medical Center. J Ky Med Assoc 1989; 87:327-31.

Schweiger JW. Oral complications following radiation therapy: a five-year retrospective report. J Prosthet Dent 1987; 58:78-82

Toljanic JA, Ali M, Haraf DJ, Vokes EE, Moran WJ, Graham L. Osteoradionecrosis of the jaws as a risk factor in radiotherapy: a report of an eight-year retrospective review. Oncol Rep 1998; 5:345-49

Van Merkesteyn JPR, Bakker DJ, Borgmeijer-Hoelen AMMJ. Hyperbaric oxygen treatment of osteoradionecrosis of the mandible: experience in 29 patients. Oral Surg Oral Med Oral Pathol 1995; 80:12-6.

DISCLAIMER: Support for People with Oral and Head and Neck Cancer, Inc. does not endorse any treatments or products mentioned in this article. Please consult your physician before using any treatments or products.

Published with permission from News From S*P*O*H*N*C, Vol. 9 No. 9 Summer 2000, a program of Support for People with Oral and Head and Neck Cancer, P.O. Box 53, Locust Valley, NY 11560-0053, 800-377-0928, www.spohnc.org.

Daniel E. Jolly, DDS, is 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 20 years and educated dental students, dental residents, dentists, dental hygienists and others over those same two decades. Dr. Jolly is an active member of the International Society for Oral Oncology and is currently Second Vice President of the American Association of Hospital Dentists.

Test Questions: Osteoradionecrosis, Oral Health and Dental Treatment

Please note: There is an administrative fee of $8 to cover a portion of grading and publication costs. This fee MUST accompany the test when it is submitted for grading. Use answer sheet opposite. APPROVED FOR ONE CONTINUING EDUCATION CREDIT -ADAA Members Only

1 Which of the following is (are) considered a preventive measure(s) in the management of potential ORN?

A. Tooth brushing 3 times a day

B. Topical fluoride

C. Extraction of diseased and at-risk teeth

D. Saliva substitutes

E. All of the above

2. A serious, debilitating and deforming complication of radiation therapy for the treatment of cancer of the head and neck is called --.

A. Osteoarthritis 

B. Osteoradionecrosis (ORN)

C. Osteomyelitis

D. PRON

E. B and D only

3. Tissue low on oxygen supply is called --.

A. Hypovascular

B. Hypocellular

C. Hypoxic

D. Chronic

4.Abnormal dryness of the mouth is --.

A. Dehiscence

B. Xerostomia

C. Osteomyelitis

D. None of the above

5. What percentage of stannous fluoride or neutral sodium fluoride is recommended for use as a means of preventing ORN?

A. 4% stannous and 2% neutral sodium fluoride

B. 40% stannous and 10% neutral sodium fluoride

C. .4% stannous and 1% neutral sodium fluoride

D. 10% stannous and 10% neutral sodium fluoride

6. At-risk teeth and diseased teeth are described as those with

A. Periapical lesions

B. Perio pockets over 4-5 mm

C. Caries extending into the pulp chamber

D. Mobility of Grade 2 or more

E. All of the above

7. Hyperbaric oxygen improves the circulation in the bone.

A. True

B. False

8. Which of the following is (are) a sign(s) or symptom(s) of Osteoradionecrosis (ORN)?

A. Teeth become loose

B. Ulceration of the mucosa

C. Exposure of the necrotic bone

D. B and C only

E. All of the above

9. Radiation affects the vascularity of the bone by eliminating or restricting the blood flow.

A. True

B. False

10. 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.

A. True

B. False

11. Maintenance of a dry oral environment is crucial to the prevention of ORN.

A. True

13. False

12. A patient receiving radiation therapy for head and neck cancer who presents with normally treatable dental disease but has poor oral hygiene history requires dental extractions rather than attempts to restore or retain the teeth.

A. True

B. False

13. Following extractions and radiation therapy, denture fabrication should be deferred how long after healing?

A. 3 months

B. 6 months

C. 9 months

D. 12 months or more

14. Leaving the denture in the patient's mouth until mucosal coverage is complete should treat denture ulcerations.

A. True

B. False

15. Treatment of Osteoradionecrosis (ORN) is by surgical resection of all necrotic tissue and primary closure of the mucosa supplemented with hyperbaric oxygen.

A. True

B. False

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Osteoradionecrosis, Oral Health and Dental Treatment

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