Dental aspects of osteoradionecrosis

Operative

Oral

Surgery

DENTAL ASPECTS OF OSTEORADIONECROSIS HAROLD H. NIEBEL, B.S., D.D.S.,” AND EDWARD W. NEENAN, B.A., D.D.S.,*+ CHICAGO, ILL. H E prevention and management of osteoradionecrosis is a controversial problem which confronts not only the radiotherapist and surgeon: but also the dentist. In this field, the dentist is occasionally required to remove teeth from patients who have received radiation to either the maxilla or the mandible during the course of cancer therapy. This operative procedure must be accomplished with a minimum of trauma to decrease the hazard of osteoradionecrosis. The danger of producing a portal of entry for oral bacteria to the supporting soft tissue and alveolar bone must be avoided in all cases. A review of the literature and a comprehensive study of nineteen cases of osteoradionecrosis were undertaken in an effort to determine the most desirable methods of managing this problem. A technique was then adopted for both the removal of teeth from irradiated tissues and the dental management of oral cancer patients. Although a discussion of radiobiology and radiophysiology is beyond the scope of this article, it must be emphasized that there is no essential difference in the biologic response of tissues to irradiation from either high- or lowvoltage x-rays, gamma rays, or beta rays. By whatever mechanism radiation energy is absorbed in a cell, a variety of changes and degrees of change become apparent. Broadly speaking, the intensity of effect depends upon the type of cell that is being irradiated and upon the dose employed. The lethal effect of radiation on living cells is the final result of the ionization produced in their collisions with the molecular components of living tissue.l Shields Warren’ states that the reaction of formed bone to radiation is primarily a lowering of vitality, which in some instances progresses to necrosis. This may occur without change in the bone’s structure or general appearance, the only indication of the injured state being a slight alteration of the osteocytes. Atrophy and eburnation of bone are recognized late radiation changes. Irradiated bone, because of the impairment of its vitality, is peculiarly sensitive to infection and trauma and these are in a large part responsible for

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From the Veterans Administration West Side Hospital, 820 S. Damen Ave., Chicago 12, Illinois. *Chief, Ingatient Dental Service. **Director, Dental Services. 1011

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irradiation ost,eomyelitis. There is little evidence IGnting to the reactions of usteocytes, osteoblasts, and osteoclasts. ivnrren also states that a pure radiation effect is infrequent in the maxilla and mandible, hut destructive lesions of these bones are conlmonly seen l)y ratliologists as a result of the combined effect of rildiatiotl and infection after treatment 01’ intraoral carcinoma. Regautl” observctl certain peculiarities of necrosis of hone following irradiation of (aarcillollla of the lmccal mu~sa and ronc~luded that bone is more ~ulneral~le that) surface epithelium. This vulneral~ility is probably inherent in the supporting substance ant1 not in t>he hone cells. There is no elective sensitivity o 1’ rlo~~~lal atlult I)ot~e to ratliatioll, but rather a diffuse radiosensitivity c~onditioned I),- (3alcification of the fundamental substance. The secontla1-y rays act nlainly on the lamellar substance, altering in some way the physical constit,ution of this sahstanve without procluc4ng gross evidence of change a s l o n g a s t h e hone relrl;lins free froitl t~*alllna and infection. An alterat,ion in the grountl snl)stil tlce is responsible for the greater susceptibility to infection and less susceptibility to histolytic solvents. which is also seen in all collagcnous substances affected by radiation. It is LaDow ‘s’ opinion that irradiation theral)y interferes with normal hone nutrition. Fle s t a t e s t h a t t h e f u n c t i o n o f t h e periosteum is altered 1)~ primary irriltliation p l u s secon;la ry effects of irradiated calcium particles within the bone. (‘ellular elements within t,he l)onr marrow spaces are also changed. l:lood vessels are oc~clutletl 1,~ thrombosis or a proliferating fibrosis. The decreased pI1 of the saliva is a result, of irradiation and could be due to (1) lessened glantll~lal* function. (2) lessened mast,icatory function due to pain or absence of teeth, or (1:) increased organisms due to poorer oral hygiene. Ewing” llas shown histol~~gically that. irradiated bone seems to present widening ant1 irregularit\.- of Iacunae ailtl canaliculi and a partial loss of lamellar* structure. I ie concludetl that these changes signified severe tlegeneration of bone cells, tlestrnction of cell processes, closure 01’ many canaliculi, and challges of’ all nntletei,rllilled llat,ure ill the latnellar substance. Kanthak” felt that this intlicatrd that thr I)one cells, themselves, are readily killed hy irradiation iLJltl thus the entire Ixjne suffers deritalization and alteration. Tn addition to these eft’ects. there is consitleral)le reactioll of the vascular supply of the hone. The vessels tent1 to l)ecome thickened and are finally obliterated. Tn addition to the tlenth of I)one ~~~~11s llotetl alcove, an aseptic type of necrosis lialrthak :I~SO stated that the relative]~~ high incidence of Df t,he b o n e OCVUI*S. osteoradiollect*osis of the ja\V.S following s-ray treatment of neoplasms of the oral (da\Tity alld co,ltiguous stl’uctures lnakcs ii. essential that al1 infectetl 01’ questionable teeth be rrmovetl ant1 that the remaining teeth ant1 related struttures he l)ut in as sountl it cv~ntlition i1.S possible prior. to treatment. I,awrence’ illso ohseryed that the mavoscopic structure of the irradiated hone conIt I)r retainetl, lmt if infebon entered the l)olle a n in(l() (lestructive pro(?rss

tlcr-eloped

w h i c h

culminated

ollly a f t e r

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sequestration and healing. lvCs II:II’(~ tided that i n d e s t r u c t i v e p r o c e s s (:llllllillilteclin the tleath of’ t h e t)atie1tt

01%

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ill

some cases this ~10~ e v e n though the

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primary carcinoma, for which the irradiation was delivered, had been eliminated Lawrence concluded that it was safer to extract all remaining teeth prior to therapy, although this point is a debatable one. Deland* makes the following observations regarding osteoradionecrosis : Devitalized teeth lead to sepsis. Teeth subjected to irradiation show recession of the surrounding mucosa. The blood supply is impaired, and pyorrhea and sepsis follow. Sepsis wreaks havoc with irradiated tissues; therefore, teeth and irradiation therapy are not compatible.

Radiation Effect on Bone The cementing or intercellular substance of bone consists of mineral salts, mainly calcium phosphate, which, upon being struck by the ionizing rays, produce damaging secondary radiation. Eecause of this high calcium content, the actual intensity of a given dose of irradiation is probably greater in bone than in the overlying skin and mucous membrane. In determining the depth

Fig.

l.-Medullary

portion of mandible which had received 6,000 r to the depth over forty-one days. Note the diffuse flbrosis.

dose received by the bone in the cases reviewed, this back-scatter irradiation was not considered. Thus, the actual dose received by the bone was unquestionably much greater than the computed dose. Woodard and Coley” state : “In the adult, radiation therapy involving the delivery of doses in excess of 3,000 r to the bone should not be used for benign lesions because of the danger of damage to the regenerative capacity of the bone. For malignant lesions, doses up to 4,000 r may be used in the

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Fig. 2 .--Destruction of osteocytes evident in mandible which had received 8,600 forty-eight

Fig. S.--New

days.

b l o o d vesse1 formation in irradiated mandible.

f o

Note the diffuse Rbrosis

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expectation that the bone, alt,hough permanently damaged, will retain a considerable degree of useful function. Doses much higher than this may cause such severe damage to bone that the final results will range from unsat,isfact,ory to disastrous. ” In three cases studied by us, where part of the mandible had received over 6,000 r and was subsequently excised, there was little microscopic evidence of complete obliterative endarteritis. The predominant change observed was the presence of a diffuse fibrosis (Fig. 1). In some areas there existed new vessel formation and telangiectasis consistent with granulation tissue formation, while other areas contained older vessels whose walls were thickened, but were not thickened to the point of lumen obliteration (Figs. 2 and 3). In the cortical bone a few lacunae were empty, showing deat,h of the contained osteocytes.

Infection Six of the nineteen cases of osteoraclionecrosis which we studied are shown in Table 1. Tt was noted that in every case either infection gained aeeess to the previously irradiated bone or there was a recurrence of the neoplasm prior to the development of necrosis. The access of organisms into the irradiated tissue appeared to be the single most consistent factor in the initiation of necrosis. We have never seen a purely aseptic case. In nine patient,s there was associated tumor recurrence. Neither age, sex, race, nor time following radiotherapy appeared to be influencing factors. Loss of vascularity, whether from radiotherapy or from vessel ligation, definitely decreases the abilit,y of tissue regeneration and resistance to bacterial invasion. This diminished blood supply thus enhances the danger of osteoradionecrosis. Eleven of the nineteen patients received x-radiation plus gamma. radiation delivered by radium in nerclles or radon seeds (Table I). The morbidity periods extended from three months to three years. Fig. 4 illustrates the course of a typical ease of osteoradionecrosis and shows both radiation caries and surgical repair of the mandible. Early diagnosis of ost,eoradionecrosis is difficult, if not impossible, for radiographic osseous changes are not apparent until the beginning of sequestration.

Management of Teeth in Irradiated Patients The removal of all teeth in the path of irradiation prior to the initiation of radiotherapy is felt to be inclicated in every case where a cancerociclal dose of x-radiation is to be delivered through multiple portals for intraoral squamous-cell carcinoma. Fig. 5 illustrates a case of periapical osteolysis following intensive radiotherapy to the mandible from which the teeth were not previously removed. Since the early organized blood clot is extremely sensitive to radiation and thus prone to breakdown, an alveolectomy should be performed in order to minimize the clot size. The buccal and/or labial alveolar plates of bone are beveled labiolingually and/or buccolingually (Fig. 6). All sharp edges are rounded and the entire process is smoothed with the bone file.

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Fig. 4.-Progress of osteoradionccrosis of the mandible extending over a period of thirty months. The ramus and part of the body were ultimately excised and replacetl with a rib graft. Note the radiation caries in C and D.

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infection resulting from teeth devitalized by irradiation. occurred over the period of one year.

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Soft-tissue flaps are tightly sutured so as to cover completely ar~tl firmly all exposed bone (Fig. 7). With this procedure, a minimum number of radiosensitive young connective-tissue cells will be formed by the organization ar1t1 t,he differentiation of the blood clot. Radiotherapy, even though protracted, should not be started for at, least fifteen days following this surgical procedure.

Fig. fi.-Raclical

alwolertomy

to minimize

clot size.

When salivary glands have been heavily irradiated, even if the teeth were not in the path of the beam, quantitative and qualitntiye changes occurring in the saliva ran ultimately result in the development of a peculiar type of caries first describetl b y tlel Regatol” (Fig. 8). The danger lies with the difficulty encounteretl in controlling this type of caries. Its continued progress evcntnally results in devitalizat,ion of teeth, with subsequent yeriapical infection and radiation necrosis (Fig. 4). The diminished quantity of sali\-a. JI~LIS its ropy consistency. adds to the patient’s difficulty in keeping his teeth free of plaque formation. In an effort to increase the saliva flow, he will frequently hold hard fruit candy it1 his mouth. The glucose augments the production of lactic acid and fnrther aggravates the already lowered pII of the saliva. This comhinat,ion of factors in all probability results in the production of the soca.lled “radiation caries.” The following observations were made in a series of ten patients who had one or more of their major salivary glands irradiated during the course of radiotherapy for carcinoma : 1. In all patients the quantity and consistency of the saliva were altered. A dry mouth was the universal complaint. The saliva that remained was of a ropy consistency. 2. The interva.1 between irradiation and the pII studies varied from two days to four years. The pII was lowe& immediately after irradiation. In one case, the pl-1 ret,urned t o 8 one year after irradiat,ion.

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B.

Fig. 7 . - A , E d ermoid tomy

Fig.

B.-Early

radiation

carcinoma involving alveolar ridge and maxillary sir LUS prior to radiotherapy. (Three days postsurgery. )

caries.

Both the field of

parotid and irradiation.

submaxillary

glands

4 1 vet llec-

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The average for the

A certain amount of cellular aiteration produced by heavy radiation is irreversible, and the vitality of the irradiated tissues is permanently lowered. a,nd the It is felt that dentures should never be placed on irradiated Gssues patient should be made aware of the danger of ora. t,rauma in order t>o avoid a,ny form of irritation, either chemical, mechanical, or thermal. It should bc emphasized that the hard and soft tissues have sust,ainetl a permanent change. resulting in a lowered resistance to mechanical tra,uma and infectious l)t*o(‘esses. Whether the diminished vitalit,y is tlue to a decrea.sed distribution of t,he blood supply to the area or a change in the capil1a.ry or cell wail I)errneability is not known. Although the exact yuantity of irradiation that is required to produce this tlegrce of change has never been determined, \ve feel that bone receiving 4,000 P or more to the depth has a permanently lowered vitality and should be treated accordingly.

Fig.

9.-Osteoradionecrosis

of the mandible. surgical

The bone was allowed to sequestrate without intervention.

Extraction of Irradiated Teeth Should extraction of teeth from heavily irradiated bone become necessary, their extrusion with the use of ela,stic hands has proved to be the technique of choice. This procedure has been used repeatedly with success and will be the subject of a later article. Although Wi1dermut.h and Cantril’l feel that teeth can be extracted with the “proper support and caution,” this opinion is not shared by others, including ourselves. Intraoral lead shielding is not and in some instances cannot be utilized as often desired, for radiation is frequently delivered through multiple portals.

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Shielding is most easily and advantageously effected in the lip and cheek areas. In one case, lead shielding was used posterior to the uvula when the radiation was delivered through an intraoral cone, and the primary lesion was limited to the uvula.

Management Two methods of treatment have been advocated for osteoradionecrosis of the mandible. The more conservative approach allows sequestration to occur, while in the radical approach the entire irradiated area on the involved side is excised and plastic repair subsequently performed. Fig. 9 illustrates a case in which the conservative method is being used. Sequestration in radionecrosis is much slower than in necrosis due to trauma and infection. Although a discussion of the treatment of osteoradionecrosis is beyond the scope of this article, it is felt that the conservative approach is the preferable one. Pain frequently is entirely absent. When severe pain does persist, it can be controlled with either deep alcohol block injections or by severance of the nerve. Soft-tissue infection is eliminated with the use of antibiotics. Premature surgical intervention endangers the life of the surrounding viable bone. We feel that waiting until the sequestrum can be removed with ease will insure a smaller loss of ha,rd and soft tissue, resulting in a minimum of disfigurement.

Conclusions 1. Even with the use of supervoltage and improved radiotherapy techniques, osteoradionecrosis will continue to be a problem that confronts the radiotherapist, surgeon, and dentist. 2. Changes occurring in bone after irradiation appear to result from cellular damage as well as impaired vascularity. Histologic examination of bone obtained from excised irradiated mandibles demonstrated some loss of vascularity. The predominant change noted was the presence of a diffuse fibrosis. 3. The access of organisms into heavily irradiated tissue appears to be the primary influencing factor in the production of osteoradionecrosis of the mandible. Other influencing factors are (a) loss of vascularity from either surgery or radiotherapy and (b) recurrent neoplasm. 4. Where radiation is used in the treatment of oral cancer, all teeth in the path of the rays should be extracted and an alveolectomy performed prior to the initiation of therapy. This applies only when a cancerocidal dose of irradiation is contemplated. 5. The conservative method of treating osteoradionecrosis is preferable to the radical method, even though the period of morbidity is increased.

References 1. Ackerman, L. V., and de1 Regato, J. A.: Cancer: Diagnosis, Treatment, and Prognosis, St. Louis, 1947, The C. V. Mosby Company, p. 99. 2. Warren, S.: Arch. Path. 34: 443, 562, 749, 917, 10’70, 1942. 3. Regaud, C.: Compt. rend. Sot. de biol. 87: 629, 1922.

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4 . I,aDow, c. s . : Osteoradiorrecrosis of the .J zw, OKAI, SCM:., @hU MED., & OIUL PATH. 3: 582, 1930. J. Bwinr. .J.: Acta radio]. 6: ::HIJ. 1926. 6 . Rantggk, P. E’.: J. Am. 1)ent. k. 28: 1925-1929, 1941. 7. Lawrence, E. A.: Am. J. I~oentgeuol 55: iSi42, 1946. X. Deland, E. M.: Radiology 52: 206, 1949. 9. Woodard, H. Q., and Cole)-. H. I,.: Am. J. Hoentgenol. 57: 464.471, 1947. IU. Del Regato, J. A.: Am. .J. .Koentgenol. 42: 404-410, 19%). 1 1 . Wildermuth, C)., and C’antril, S . ‘ I ’ . : R a d i a t i o n N e c r o s i s o f t h e M a n d i b l e , R a d i o l o g y 6 1 : ‘771-785, 195X,