Autogenous cancellous-marrow bone grafts irradiated mandibles Robert D. Marciani, D.M.D.,” Arthur A. Gonty, D.D.S.,** J. S. Giansanti, D.M.D., M.S.D.,*** and Jose Avila, M.D.,**** Lexington, Ky. VETERANS SURGERY,
ADMINISTRATION COLLEGE
HOSPITAL
OF DENTISTRY,
AND TJNIVERSITY
A pilot study was conducted to investigate cancellous-marrow grafts in irradiated tissue. large mandibles were used in this preliminary ceived 500 rads of cobalt irradiation twice a were created in the mandible and reconstructed row graft. Bony union occurred in all the formed in the surgical defect varied. The generally similar to the nonsurgical side.
THE
DEPARTMENT
OF
ORAL
OF KENTUCKY
the osteogenic potential of autogenous Three young adult mongrel dogs with experiment. Each dog mandible reweek for 5 weeks. Discontinuity defects immediately with a cancellous-marmandibles. The quantity of new bone graft sites showed a histologic picture
T
raumatic or surgically created discontinuity defects of the mandible have been successfully restored by cancellous-marrow grafts. Although the treatment of choice in many situations, this method of reconstruction has not been widely reported for the repair of defects in mandibles previously exposed to irradiation therapy. For that reason, this project was initiated as a pilot study to investigate the osteogenic potential of autogenous cancellous-marrow grafts supported by titanium baskets in irradiated tissue. ‘I’he objectives of the investigation were (1) to study clinically the tolerance of irradiated tissue to titanium mesh, (2) to observe clinical evidence of graft success or failure, and (3) to study the histology of the graft site compared to that of the uninvolved contralateral side. *Staff Oral Surgeon, VA Hospital, and Associate Professor, Department of Oral Surgery, University of Kentucky College of Dentistry. **Assistant Professor, Department of Oral Surgery, University of Kentucky College of Dentistry. ***Professor, Department of Oral Pathology, University of Kentucky College of Dentistry. ****Assistant Professor, Department of Radiation Medicine, University of Kentucky College of Medicine.
365
364
Marciani
et al.
Fig. 1. A 4 cm. discontinuity Fig. 8. Titanium mesh basket dibular continuity.
Oral March,
defect packed
surgically created with autogenous
Surg. 1977
in the body of the mandible. cancellous marrow restoring man-
It is generally agreed that bone grafts are most successful when the recipient site is well vascularized, soft tissue is plentiful, and the surgical site is free of infection. For this reason, malignant tumors of the oral cavity treated by a combination of irradiation and surgery resulting in discontinuity defects of the mandible usually present a major reconstruction dilemma. The soft tissue available to create a graft bed is often densely fibrotic and in short supply. In bone, absorption of large amounts of irradiation may cause death of osteocytes, vascular disturbances, destruction of marrow, and reduction or complete loss of bone vitality. In 1926 Ewing1 reported that moderate and severe radiation reduces the vitality and growth capacity of bone cells and compromises their bone-forming function. GowgieP experimentally studied the effects of a 7,500 r dose of orthovoltage on monkey mandibles. A fatty and acellular marrow resulted. Blood vessel walls in the body of the mandible were thickened. These vascular changes uniformly involved the arterioles, whereas medium- and large-sized arteries were only occasionally involved. Capillaries and veins were not affected. The over-all
Volume Number
43 3
Cancellous-marrow
Pig. 3. Dog No. 278. Complete regeneration of bone in the is indistinguishable from the adjacent bone. Fig. 4. Dog No. 271. The lingual aspect of the mesh is partially The full contour of the surgical site is not restored.
graft
bone grafts
site.
embedded
The in
grafted osseous
367
area tissue.
effect of irradiation was to limit bone production and favor bone resorption. Our interest in this project was to det,ermine whether these radiation effects would specifically apply to autogenous cancellous-marrow grafts and compromise the successof a well-established, usually successful, reconstructive procedure. METHOD Three young adult mongrel dogs with large mandibles were selected for this preliminary study (Dogs Nos. 271, 275, and 278). Two of the dogs (Nos. 275 and 278) were subjected to extraction of all their teeth. Only the mandibular teeth were extracted from the third dog. All the extractions were performed prior to irradiation. The extraction wounds were allowed to heal for approximately 7 weeks. The three animals. were subsequently irradiated over the same period of time. Each dog received ten treatments of cobalt-60 irradiation during a 32-day period. A total of 4,100 rads were administered (410 rads per treatment). The dose was calculated at the midsagittal plane and administered from laterally opposed ports (205 rads per port). The field size was 5 by 15 cm., with the lower lip forming the anterior boundary of the field. The field extended beyond the ramus posteriorly and below the mandible inferiorly. The commissure of the lip provided the superior boundary. (Irradiation was conducted with the mouth open and the maxilla out of the field.) The radiation equivalent therapy dose (RET) was 1,610. This dosewas calculated to duplicate a presurgical irradiation protocol of 1,600 RET commonly used to treat oral carcinoma in human beings (200 rads per day over a 5-week period.) All the animals tolerated the dental extractions and the subsequent irradiation well. They were housed in standard laboratory cages and were fed a highprotein soft diet. There was no significant alteration in the well-being of the animals. Three weeks after irradiation, unilateral partial mandibulectomies were performed on each dog (Fig. 1). Surgical accesswas gained through a submandibular midline skin incision extending from the anterior mandible to a point opposite
368
Marcia&
et al.
Oral March,
Surg. 1977
the mandibular angle. A full-thickness skin flap was developed laterally over the right mandible. The periosteum covering the lateral and medial surfaces of the jaw was excised and removed from the animal. A 4 cm. discontinuity defect of the mandibular body was created and immediately restored with an autogenous cancellous-marrow graft. The bone was collected from the iliac crest and supported in the defect by a titanium mesh basket (Fig. 2). The wound was closed in layers. Intermaxillary fixation was not used. Each dog recevied 2 ml. of Tylan 200 for 3 days. There were no significant, initial postoperative complications. The dogs were examined clinically at regular intervals. Six months following graft placement, the three animals were killed. Their mandibles were removed and placed in 10 per cent formalin with subsequent decalcification in 5 per cent formic acid. Specimens mere taken for microscopic inspection from the graft site a.nd from the mandibular body of the contralateral side. After decalcification, dehydration, and infiltration with paraffin, sections were cut at &.L, and stained with hematoxylin and eosin. CLINICAL
OBSERVATIONS
At the time of being put to death, dog No. 278 was completely healed intraorally and extraorally (Fig. 3). Neither mandibular bone nor titanium basket was visible in the oral cavity. The continuity of the mandible had been restored and the full height, width, and depth of the original defect were completely reconstituted. Bone in the grafted area was indistinguishable from adjacent hard tissue and exceeded the boundaries of the autogenous transplant. The titanium mesh basket was firmly fixed at the operative site. The superior lingual portion of the mesh basket was visible intraorally in dog No. 275. The adjacent alveolar and lingual mucosa otherwise appeared normal. Bony union was complete and firm. The gross examination of the mandible at necropsy was similar to that of dog No. 278. Mucosal ulceration was significant in dog No. 271. Virtually t.he entire superior buccal surface of the mesh and a smaller segment of the lingual portion of the basket were exposed. Firm clinical union, however, had been achieved (Fig. 1). The lingual aspect of the mesh was partially embedded in osseoustissue but bone production at the graft site was considerably less than in the other dogs. The full contour of the mandible was not restored and the titanium basket was loose and freely movable. HISTOLOGIC
OBSERVATIONS
The over-all architecture and morphology of all the nongrafted left mandibles were normal. The bone consisted almost entirely of cortical and trabecular lamellar bone. There did not appear to be any reduction in the number of viable osteocytes within the lacunae. ‘I’he vascularity within the bone did not exhibit any obvious pathosis. Normal trabeculae, prominent nerve bundles, and vascular channels were seen in the medullary portions of the bone. The marrow was entirely of the fibrofatty type (Fig. 5). Occasional small foci of osteoblastic activity were found. A few osteoclasts were also noted. In general, however, the degree of osteoblastic and osteoclastic activity was minimal. The periosteum appeared
Volume Number
Fig. 5. Dog No. 271. irradiated mandible. Fig. 6. Dog No. 275. and irradiated mandible but
Cancellous-marrow
43 3
A representative section (Hematoxylin and eosin; A representative section (Hematoxylin and eosin;
bone
grafts
369
of the fibrofatty marrow of the nongrafted x15.) of the hematopoietic marrow of the grafted x40.)
to be normal, and there was no evidence of subperiosteal osteoblastic activity. The graft sites showed a histologic picture generally similar to that of the nonsurgical side. The major difference was the abundance of hematopoietic marrow in the graft sites (Fig. 6). Hematopoiesis was least prominent in the graft site of dog No. 278 and, comparatively, it most closely resembled the bone of the nongrafted side. The subperiosteal and endosteal surfaces of dog No. 275 exhibited osteoblastic activity. The interstices of the bone consisted of an admixture of both fibrofatty and hematopoietic bone marrow. The surrounding soft tissue was densely fibrous, containing a small sequestrum of nonviable bone. There was a pronounced focal inflammatory cell infiltrate near the soft tissue covering. The mandible of dog No. 271 was morphologically split into two seg-
370
Marciani
et al.
Oral March,
Surg. 1977
ments. One of these segments consisted entirely of dense, predominantly lamellar bone. Osteoblastic activity was apparent along the trabecular surfaces and much of the periosteal covering showed prominent osteoblastic activity. Foci of acute and chronic inflammatory cells were found in the medullary spaces of the bone and in the surrounding soft tissue. The second part, of this same specimen consisted of approximately equal amounts of woven and lamellar bone. Osteoblastic activity was prominent with few osteoclasts present. A dense infiltration of acute and chronic inflammatory cells was seen. The bone in both sections contained a large number of viable osteocytes. DISCUSSION Several impressions from the literature are worthy of discussion. Therapeutic doses of irradiation are known to reduce the growth capacity of bone cells and compromise their bone-forming function. 1, 2 This direct effect on bone cells significantly alters the ability of bone to repair itself. Further interference with bone production results from alterations in blood vessels and available blood supply. Decreasing circulation undoubtedly contributes to the increased incidence of infection of irradiated mandibles. Likewise, considerable morphologic and functional alteration has been observed in the salivary glands of dogs receiving 1,750 I” of 200 kv. radiation locally to the head.3 In addition, there are often associated soft tissue changes observed including stomatitis, surface sloughing, oral hemorrhage, erythema of exposed areas, and epilation. All of these changes are frequently seen in the irradiated human patient, Even in an edentulous situation, the effects of reduced salivary flow are very important. An already radiation-atrophied alveolar mucosa is rendered more fragile and susceptible to injury from both internal and external agents. This increased friability places the underlying mandibular bone at a greater risk of exposure to the oral environment. When irradiated bone is so exposed, intraosseous infection usually follows with all the concomitant implications of osteoradionecrosis. Despite the inherent viability of the autogenous cancellous-marrow grafts, it is logical to assume that they may fare badly in such a potentially poor environment. In our study, however, the grafts enjoyed relative success. Continuity of the mandible was restored in each of the three animals previously irradiated with megavoltage doses equivalent to some commonly used human irradiation protocols. As noted, however, the “successes” were variable. Only one of the dogs could be considered to be without clinical problems at the end of the 6-month period. One of the animals had developed a relatively small ulceration with exposure of a portion of the titanium mesh. This minor problem persisted to the time of necropsy. The third dog had developed extensive mucosal ulceration that, despite restoration of mandibular continuity, significantly inhibited the total reconstitution of the surgical defect. The latter case would have to be considered a major clinical problem. It is difficult to draw conclusive inferences from this pilot study for several reasons: (1) The number of animals was small. (2) The animal chosen as the study model does not necessarily duplicate the human subject and may respond
Volume Number
43 3
Cancellous-marrow
bone grafts
371
differently to an adverse environment. (3) The surgical defect created did not exactly reproduce the usual morphologic picture seen in en bloc oral tumor dissections encompassing the mandible, adjacent soft tissue, and radical neck resection. In our study, soft-tissue loss was minimal. Major blood vesselswere not interrupted. The abundance of soft tissue and the relatively superior blood supply undoubtedly contributed significantly to the successof the grafts. The inherent resistence of the animal to infection may be another major factor. (In one animal a considerable portion of the graft was exposed to the oral environment, but bone was still produced. ) The histomorphology of the unoperated left mandible reflected some of the changes reported in earlier studies of irradiated bone.‘, 2 The marrow was fibrofatty, but the vascularity within the bone did not exhibit any obvious pathologic change. The histologic changes in the unoperated mandibular body will be closely monitored in our future studies. In our clinical experience with human patients, the alleged “bone-sparing effect” of megavoltage irradiation has not decreased the incidence of osteoradionecrosis.4 It may, however, provide an improved environment for cancellousmarrow grafts. (Clearly, the degree of histologic alteration of irradiated bone is directly related to the dose received, irrespective of the type of irradiation. Our subsequent studies will include irradiation levels above usual preoperative doses.) Interestingly, the graft sites appeared more vascular. The interstices supported both fibrofatty and hematopoietic marrow. We suspect that this microscopic picture may change in future studies in which the specimens will be examined one year or more after graft placement. We believe the results of this pilot study suggest that cancellous-marrow bone grafts can be successful in subjects receiving therapeutic irradiation at lower megavoltage doses. Additional animals at similar dosage levels are presently being studied to further confirm this impression. Subsequent investigations of this technique at high levels of irradiation are likewise being planned. SUMMARY A pilot study was conducted to investigate the osteogenic potential of autogenous cancellous-marrow grafts placed in irradiated tissue. Three dogs received 4,100 rads in ten treatments over 32 days. Postirradiation discontinuity mandibular defects were created. These defects were restored with cancellous-marrow autogenous bone supported in position by a titanium mesh basket. Bony union occurred in all the mandibles. The titanium mesh partially eroded through the oral mucosa in two animals. The quantity of new bone formed in the surgical defect varied. Two dogs had complete restoration of the resected mandible. Histologic observations were documented in both the graft area and the surgically uninvolved contralateral side of the mandible.
REFERENCES
1. Ewing, J.: Radiation Osteitis, 2. Gowgrel, J. M.: Experimental 1960.
Acta Radiol. 6: 399-412, 1926. Radio-Osteonecrosis of the Jaws,
J. Dent.
Res.
39:
176-197,
372
Marciani
Oral March.
et al.
Surg. 1977
3. English, J. A., Wheatcroft, M. G., Lyon, H. W., and Miller, C.: Long-Term Observations of Radiation Changes in Sabvery Glands and the General Effects of 1000 R to 1,750 R of X-ray Radiation Locally Administered to the Heads of Dogs, ORAL SURG. 8: 87-99, 1955. 4. Marciani, R. D., and Plezia, R. A.: Osteoradionecrosis of the Mandible, J. Oral Surg. 32: 435-440, 1974. Reprint requests to : Dr. Robert D. Marciani Department of Oral Surgery University of Kentucky Medical Lexington, Ky. 40506
Center
ADMINISTRATION COLLEGE
HOSPITAL
OF DENTISTRY,
AND TJNIVERSITY
A pilot study was conducted to investigate cancellous-marrow grafts in irradiated tissue. large mandibles were used in this preliminary ceived 500 rads of cobalt irradiation twice a were created in the mandible and reconstructed row graft. Bony union occurred in all the formed in the surgical defect varied. The generally similar to the nonsurgical side.
THE
DEPARTMENT
OF
ORAL
OF KENTUCKY
the osteogenic potential of autogenous Three young adult mongrel dogs with experiment. Each dog mandible reweek for 5 weeks. Discontinuity defects immediately with a cancellous-marmandibles. The quantity of new bone graft sites showed a histologic picture
T
raumatic or surgically created discontinuity defects of the mandible have been successfully restored by cancellous-marrow grafts. Although the treatment of choice in many situations, this method of reconstruction has not been widely reported for the repair of defects in mandibles previously exposed to irradiation therapy. For that reason, this project was initiated as a pilot study to investigate the osteogenic potential of autogenous cancellous-marrow grafts supported by titanium baskets in irradiated tissue. ‘I’he objectives of the investigation were (1) to study clinically the tolerance of irradiated tissue to titanium mesh, (2) to observe clinical evidence of graft success or failure, and (3) to study the histology of the graft site compared to that of the uninvolved contralateral side. *Staff Oral Surgeon, VA Hospital, and Associate Professor, Department of Oral Surgery, University of Kentucky College of Dentistry. **Assistant Professor, Department of Oral Surgery, University of Kentucky College of Dentistry. ***Professor, Department of Oral Pathology, University of Kentucky College of Dentistry. ****Assistant Professor, Department of Radiation Medicine, University of Kentucky College of Medicine.
365
364
Marciani
et al.
Fig. 1. A 4 cm. discontinuity Fig. 8. Titanium mesh basket dibular continuity.
Oral March,
defect packed
surgically created with autogenous
Surg. 1977
in the body of the mandible. cancellous marrow restoring man-
It is generally agreed that bone grafts are most successful when the recipient site is well vascularized, soft tissue is plentiful, and the surgical site is free of infection. For this reason, malignant tumors of the oral cavity treated by a combination of irradiation and surgery resulting in discontinuity defects of the mandible usually present a major reconstruction dilemma. The soft tissue available to create a graft bed is often densely fibrotic and in short supply. In bone, absorption of large amounts of irradiation may cause death of osteocytes, vascular disturbances, destruction of marrow, and reduction or complete loss of bone vitality. In 1926 Ewing1 reported that moderate and severe radiation reduces the vitality and growth capacity of bone cells and compromises their bone-forming function. GowgieP experimentally studied the effects of a 7,500 r dose of orthovoltage on monkey mandibles. A fatty and acellular marrow resulted. Blood vessel walls in the body of the mandible were thickened. These vascular changes uniformly involved the arterioles, whereas medium- and large-sized arteries were only occasionally involved. Capillaries and veins were not affected. The over-all
Volume Number
43 3
Cancellous-marrow
Pig. 3. Dog No. 278. Complete regeneration of bone in the is indistinguishable from the adjacent bone. Fig. 4. Dog No. 271. The lingual aspect of the mesh is partially The full contour of the surgical site is not restored.
graft
bone grafts
site.
embedded
The in
grafted osseous
367
area tissue.
effect of irradiation was to limit bone production and favor bone resorption. Our interest in this project was to det,ermine whether these radiation effects would specifically apply to autogenous cancellous-marrow grafts and compromise the successof a well-established, usually successful, reconstructive procedure. METHOD Three young adult mongrel dogs with large mandibles were selected for this preliminary study (Dogs Nos. 271, 275, and 278). Two of the dogs (Nos. 275 and 278) were subjected to extraction of all their teeth. Only the mandibular teeth were extracted from the third dog. All the extractions were performed prior to irradiation. The extraction wounds were allowed to heal for approximately 7 weeks. The three animals. were subsequently irradiated over the same period of time. Each dog received ten treatments of cobalt-60 irradiation during a 32-day period. A total of 4,100 rads were administered (410 rads per treatment). The dose was calculated at the midsagittal plane and administered from laterally opposed ports (205 rads per port). The field size was 5 by 15 cm., with the lower lip forming the anterior boundary of the field. The field extended beyond the ramus posteriorly and below the mandible inferiorly. The commissure of the lip provided the superior boundary. (Irradiation was conducted with the mouth open and the maxilla out of the field.) The radiation equivalent therapy dose (RET) was 1,610. This dosewas calculated to duplicate a presurgical irradiation protocol of 1,600 RET commonly used to treat oral carcinoma in human beings (200 rads per day over a 5-week period.) All the animals tolerated the dental extractions and the subsequent irradiation well. They were housed in standard laboratory cages and were fed a highprotein soft diet. There was no significant alteration in the well-being of the animals. Three weeks after irradiation, unilateral partial mandibulectomies were performed on each dog (Fig. 1). Surgical accesswas gained through a submandibular midline skin incision extending from the anterior mandible to a point opposite
368
Marcia&
et al.
Oral March,
Surg. 1977
the mandibular angle. A full-thickness skin flap was developed laterally over the right mandible. The periosteum covering the lateral and medial surfaces of the jaw was excised and removed from the animal. A 4 cm. discontinuity defect of the mandibular body was created and immediately restored with an autogenous cancellous-marrow graft. The bone was collected from the iliac crest and supported in the defect by a titanium mesh basket (Fig. 2). The wound was closed in layers. Intermaxillary fixation was not used. Each dog recevied 2 ml. of Tylan 200 for 3 days. There were no significant, initial postoperative complications. The dogs were examined clinically at regular intervals. Six months following graft placement, the three animals were killed. Their mandibles were removed and placed in 10 per cent formalin with subsequent decalcification in 5 per cent formic acid. Specimens mere taken for microscopic inspection from the graft site a.nd from the mandibular body of the contralateral side. After decalcification, dehydration, and infiltration with paraffin, sections were cut at &.L, and stained with hematoxylin and eosin. CLINICAL
OBSERVATIONS
At the time of being put to death, dog No. 278 was completely healed intraorally and extraorally (Fig. 3). Neither mandibular bone nor titanium basket was visible in the oral cavity. The continuity of the mandible had been restored and the full height, width, and depth of the original defect were completely reconstituted. Bone in the grafted area was indistinguishable from adjacent hard tissue and exceeded the boundaries of the autogenous transplant. The titanium mesh basket was firmly fixed at the operative site. The superior lingual portion of the mesh basket was visible intraorally in dog No. 275. The adjacent alveolar and lingual mucosa otherwise appeared normal. Bony union was complete and firm. The gross examination of the mandible at necropsy was similar to that of dog No. 278. Mucosal ulceration was significant in dog No. 271. Virtually t.he entire superior buccal surface of the mesh and a smaller segment of the lingual portion of the basket were exposed. Firm clinical union, however, had been achieved (Fig. 1). The lingual aspect of the mesh was partially embedded in osseoustissue but bone production at the graft site was considerably less than in the other dogs. The full contour of the mandible was not restored and the titanium basket was loose and freely movable. HISTOLOGIC
OBSERVATIONS
The over-all architecture and morphology of all the nongrafted left mandibles were normal. The bone consisted almost entirely of cortical and trabecular lamellar bone. There did not appear to be any reduction in the number of viable osteocytes within the lacunae. ‘I’he vascularity within the bone did not exhibit any obvious pathosis. Normal trabeculae, prominent nerve bundles, and vascular channels were seen in the medullary portions of the bone. The marrow was entirely of the fibrofatty type (Fig. 5). Occasional small foci of osteoblastic activity were found. A few osteoclasts were also noted. In general, however, the degree of osteoblastic and osteoclastic activity was minimal. The periosteum appeared
Volume Number
Fig. 5. Dog No. 271. irradiated mandible. Fig. 6. Dog No. 275. and irradiated mandible but
Cancellous-marrow
43 3
A representative section (Hematoxylin and eosin; A representative section (Hematoxylin and eosin;
bone
grafts
369
of the fibrofatty marrow of the nongrafted x15.) of the hematopoietic marrow of the grafted x40.)
to be normal, and there was no evidence of subperiosteal osteoblastic activity. The graft sites showed a histologic picture generally similar to that of the nonsurgical side. The major difference was the abundance of hematopoietic marrow in the graft sites (Fig. 6). Hematopoiesis was least prominent in the graft site of dog No. 278 and, comparatively, it most closely resembled the bone of the nongrafted side. The subperiosteal and endosteal surfaces of dog No. 275 exhibited osteoblastic activity. The interstices of the bone consisted of an admixture of both fibrofatty and hematopoietic bone marrow. The surrounding soft tissue was densely fibrous, containing a small sequestrum of nonviable bone. There was a pronounced focal inflammatory cell infiltrate near the soft tissue covering. The mandible of dog No. 271 was morphologically split into two seg-
370
Marciani
et al.
Oral March,
Surg. 1977
ments. One of these segments consisted entirely of dense, predominantly lamellar bone. Osteoblastic activity was apparent along the trabecular surfaces and much of the periosteal covering showed prominent osteoblastic activity. Foci of acute and chronic inflammatory cells were found in the medullary spaces of the bone and in the surrounding soft tissue. The second part, of this same specimen consisted of approximately equal amounts of woven and lamellar bone. Osteoblastic activity was prominent with few osteoclasts present. A dense infiltration of acute and chronic inflammatory cells was seen. The bone in both sections contained a large number of viable osteocytes. DISCUSSION Several impressions from the literature are worthy of discussion. Therapeutic doses of irradiation are known to reduce the growth capacity of bone cells and compromise their bone-forming function. 1, 2 This direct effect on bone cells significantly alters the ability of bone to repair itself. Further interference with bone production results from alterations in blood vessels and available blood supply. Decreasing circulation undoubtedly contributes to the increased incidence of infection of irradiated mandibles. Likewise, considerable morphologic and functional alteration has been observed in the salivary glands of dogs receiving 1,750 I” of 200 kv. radiation locally to the head.3 In addition, there are often associated soft tissue changes observed including stomatitis, surface sloughing, oral hemorrhage, erythema of exposed areas, and epilation. All of these changes are frequently seen in the irradiated human patient, Even in an edentulous situation, the effects of reduced salivary flow are very important. An already radiation-atrophied alveolar mucosa is rendered more fragile and susceptible to injury from both internal and external agents. This increased friability places the underlying mandibular bone at a greater risk of exposure to the oral environment. When irradiated bone is so exposed, intraosseous infection usually follows with all the concomitant implications of osteoradionecrosis. Despite the inherent viability of the autogenous cancellous-marrow grafts, it is logical to assume that they may fare badly in such a potentially poor environment. In our study, however, the grafts enjoyed relative success. Continuity of the mandible was restored in each of the three animals previously irradiated with megavoltage doses equivalent to some commonly used human irradiation protocols. As noted, however, the “successes” were variable. Only one of the dogs could be considered to be without clinical problems at the end of the 6-month period. One of the animals had developed a relatively small ulceration with exposure of a portion of the titanium mesh. This minor problem persisted to the time of necropsy. The third dog had developed extensive mucosal ulceration that, despite restoration of mandibular continuity, significantly inhibited the total reconstitution of the surgical defect. The latter case would have to be considered a major clinical problem. It is difficult to draw conclusive inferences from this pilot study for several reasons: (1) The number of animals was small. (2) The animal chosen as the study model does not necessarily duplicate the human subject and may respond
Volume Number
43 3
Cancellous-marrow
bone grafts
371
differently to an adverse environment. (3) The surgical defect created did not exactly reproduce the usual morphologic picture seen in en bloc oral tumor dissections encompassing the mandible, adjacent soft tissue, and radical neck resection. In our study, soft-tissue loss was minimal. Major blood vesselswere not interrupted. The abundance of soft tissue and the relatively superior blood supply undoubtedly contributed significantly to the successof the grafts. The inherent resistence of the animal to infection may be another major factor. (In one animal a considerable portion of the graft was exposed to the oral environment, but bone was still produced. ) The histomorphology of the unoperated left mandible reflected some of the changes reported in earlier studies of irradiated bone.‘, 2 The marrow was fibrofatty, but the vascularity within the bone did not exhibit any obvious pathologic change. The histologic changes in the unoperated mandibular body will be closely monitored in our future studies. In our clinical experience with human patients, the alleged “bone-sparing effect” of megavoltage irradiation has not decreased the incidence of osteoradionecrosis.4 It may, however, provide an improved environment for cancellousmarrow grafts. (Clearly, the degree of histologic alteration of irradiated bone is directly related to the dose received, irrespective of the type of irradiation. Our subsequent studies will include irradiation levels above usual preoperative doses.) Interestingly, the graft sites appeared more vascular. The interstices supported both fibrofatty and hematopoietic marrow. We suspect that this microscopic picture may change in future studies in which the specimens will be examined one year or more after graft placement. We believe the results of this pilot study suggest that cancellous-marrow bone grafts can be successful in subjects receiving therapeutic irradiation at lower megavoltage doses. Additional animals at similar dosage levels are presently being studied to further confirm this impression. Subsequent investigations of this technique at high levels of irradiation are likewise being planned. SUMMARY A pilot study was conducted to investigate the osteogenic potential of autogenous cancellous-marrow grafts placed in irradiated tissue. Three dogs received 4,100 rads in ten treatments over 32 days. Postirradiation discontinuity mandibular defects were created. These defects were restored with cancellous-marrow autogenous bone supported in position by a titanium mesh basket. Bony union occurred in all the mandibles. The titanium mesh partially eroded through the oral mucosa in two animals. The quantity of new bone formed in the surgical defect varied. Two dogs had complete restoration of the resected mandible. Histologic observations were documented in both the graft area and the surgically uninvolved contralateral side of the mandible.
REFERENCES
1. Ewing, J.: Radiation Osteitis, 2. Gowgrel, J. M.: Experimental 1960.
Acta Radiol. 6: 399-412, 1926. Radio-Osteonecrosis of the Jaws,
J. Dent.
Res.
39:
176-197,
372
Marciani
Oral March.
et al.
Surg. 1977
3. English, J. A., Wheatcroft, M. G., Lyon, H. W., and Miller, C.: Long-Term Observations of Radiation Changes in Sabvery Glands and the General Effects of 1000 R to 1,750 R of X-ray Radiation Locally Administered to the Heads of Dogs, ORAL SURG. 8: 87-99, 1955. 4. Marciani, R. D., and Plezia, R. A.: Osteoradionecrosis of the Mandible, J. Oral Surg. 32: 435-440, 1974. Reprint requests to : Dr. Robert D. Marciani Department of Oral Surgery University of Kentucky Medical Lexington, Ky. 40506
Center
