Use of homologous bone in maxillofacial surgery

J Oral Maxillolac Surg 51:1181-1193.1993

Use of Homologous Bone in Maxillofacial Surgery EDWARD ELLIS III, DDS, MS,* AND DOUGLAS P. SINN, DDSt Homologous bone grafts were used in 135 maxillofacial surgical procedures. including acute midfacial fracture repair (n = 77), elective osteotomies of the facial bones (n = 35), secondary correction of traumatic deformities (n = 6), mandibular reconstruction (n = 10). facial bone augmentation (n = 5), and reconstruction of maxillary tumor defects (n = 2). Postsurgical complications occurred in five of the patients. This article reviews the rationale for using homologous bone grafts, their immune response, how they heal, and the risk of transmission of disease.

Although several types of bone grafts are available for use in reconstructive surgery, autogenous bone is the type used most frequently. It can be obtained from a host of sites within the body and can be taken in several forms. The advantages of autogenous bone are that it provides osteogenic cells for the first phase of bone formation and that it does not trigger an immunologic response. The disadvantage of autogenous bone is that it necessitates another site ofoperation for procurement of the graft. Homologous grafts, also known as allografts or allogeneic grafts, are taken from another individual within the same species. In 1968, Urist stated, "Neither undecalcified nor decalcified allogeneic bone grafts are rated equal to fresh, warm, autologous bone for repair of large bone defects in adult individuals."! After another 20 years of research, it is probably fair to say that that statement still remains true today.r" However, major problems in the use of autogenous bone grafts exist. Most important is donor site morbidity. Further, a limited amount ofautogenous bone is available, particularly in infants and children. For large defects, obtaining adequate autogenous bone can be challenging. The search for a suitable alternative to autologous grafts has led to the use of homologous (allogeneic) bone of various preparations. Today, the most commonly used homologous bone is freeze-dried. Any of Received from the Department ofOral and Maxillofacial Surgery, Un iversity of Te xas Southwestern Med ical Center, Dallas, TX. • Associate Professor. t Professor and Chairman. Address correspondence a nd reprint requ ests to Dr Ellis: Division ofOral and Maxillofacial Surgery, Uni versity ofTexas Southwestern Med ical Center, 5323 Harry Hin es Blvd, Dallas. TX 75235-9109.

© 1993 American Association of Oral and Maxillofacial Surgeons 0278 -2391/93/5111-0003$3.00/0

the treatments used to eliminate the immunologic respon se destroys remaining osteogenic cells within the graft and, therefore, homologous bone grafts cannot participate in the first phase ofosteogenesis. Their contribution to osteogenesis is purely passive, offering a hard tissue matrix for the second phase of osteogenesis, bone induction. Thus, the host must produce all ofthe essential elements in the graft bed for the homologous bone graft to become incorporated. The advantages of homologous bone are that another site of operation in the host is obviated and that a similar bone or a bone ofsimilar shape to that which is being replaced can be procured . The disadvantage of homologous bone is that it does not provide viable cells for the first phase of osteogenesis. This article reviews our experience with homologous bone when used for a variety of maxillofacial surgical procedures.

Materials All patients in whom homologous bone was used by the Oral and Maxillofacial Surgery service between July I, 1988 and December 31, 1991 were included in this review. Any patient with less than 12 weeks of folIowup was excluded. The following information was obtained from patient records: pati ent age and sex; type ofsurgery performed ; type and amount of homologous bone graft used; ' location of bone graft placement; method of securing bone graft; and postsurgical complications, defined as infection of the graft site, need for graft removal, spontaneous exfoliation of graft, or nonunion. The bone was obtained from The University of Texas Southwestern Transplant Services Center. This is a fulIservice tissue bank accredited by the American Association of Tissue Banks and the Eye Bank Association of America. Donors are screened for communicable 1181

Table 1.

.... .... oe

Uses of Homologous Bone in Patient Sample No, of Patients

Mean /\ ge (yr) (Range)

37

Orbital/n aso-orbitoethmoid fractures

Panmidfacial fractures

Diagnosis Primary treatment of facial fractures Zygcmnticomaxillary complex fractures

Midfacial osteotomies Le Fort I

Le Fort III

Segmental dentoalveolar

Mandibular osteoto mies Mandibular hypoplasia

I\)

Type of Done Graft

Location of Bone Graft Placement

Method of Done Graft Fixation

29 (14-86)

Rib (n = 29). ilium (n = 6). decalcified rib (n = 2)

Orb FI (n = 22). Ant M:lX (n = 9). Orb 1'1 + Ant Max (n = 6)

Lugscrew(s) (n = 28). bone platets) (n = 6). no lixation (n = 2)

24

26 ( 16·Sf»

Rib (n = 19), ilium (n = 4). fibula + rib (n = I)

Orb FI (n = I I). Orb R + medial wall (n = 9). medial wall (n = 3). Orb R + medial wall + nasal dorsum (n = I)

Lag serew(s) (n = I'», bone plate(s) (n = 3). no fixution (n = 3)

16

32 (20-66)

Rib (n = 15), decalcified rib (n = I)

Orb R + Ant Max (n = 12). AnI Max (n = 3). Orb R (n = I)

Lugscrcwts) (n = 15). bone plate (n = I)

patient brought in large sequestrum from AnI Max at 9 months' postsurgerysoft tissue healed. No secondary surgery necessary,

12

23 (6-48)

Fibula (n = 4). tibia (n = 3). rib (n = 2). ilium (n = 2). femur (n = I)

Ant Max wall (n = 9). intcrpositional (n = 3)

Lugscrews (n = 9), no fixation' (n = 3)

patient whose gmft was used intcrpositionally for vertical midface augmentation developed Iibrous union in spite of Ihe fact the maxilla was stabilized with plates and screws.

Rib + ilium (n = 5), ilium (n = I)

Lateral orbit. nasofrontal j unction, ntcrygc maxillary j unction. internal orbital walls. nasofrontal area (n = 6)

Lugscrews and microplates (n

Ilium cancellous blocks (both)

Alcvolar defects after repositioning segments

No fixation

Ilium cancellous blocks

Intcrpositional between defects from invcrtcd-L osteotomies

Fixation across invertedL bone segmentsnone through bone grafts

6

2

8 (4-13)

3 1 &. 36

= 6)

Postoperat ive Complications

patient with soft tissue dehiscence over Ant M:lX bone grafts, Conservative dcbridcmcnt-c-soft tissuc covered.

::r:

...0

<3r-

0 C> 0 c: en t:C

0 Z m

...Z

>

X

r=r0

~

o

sr-

(,

II

(5-18)

en

c:;a

C> rn :;a

-<

m

lntcrpositional genioplasties

Seconda ry correction or trau matic defects Enophthalmos status post zygom:nieom:lxillary clllnplcx{orhital fractures

Frontal-suprnnrbital rim defect Mandibular reconstruction Itc miutandibulcctorny defect

9

19 ( 16·36)

Ilium cancellous blocks

Interpositional between inferiorly repositioned genial segment

rrVi

Wedged into place between hone fragments

>

Z 0

C/l

5

2X (22-34)

I

36

4

32 (15-41)

Rih (n n 2). fibular (n n 2). ilium (n = I)

Internal orhit-floor and medial wall (n = 5)

No fixation (n = 3). lag screws (n n I). hone plates (n = I)

Ilium

Right forehead

Lag screws + hone plates

lIem imandiblc (n = 3). split ribs (n = I). (hOlh had particulate autologous hone grafts)

!lone screws/wires (n 4)

=

Z Z

15·year-old boy developed chronic infection requiring debrldcmcnt of' ramus portion of hone graft 4 months postoperat ively. 26·ycar-old woman developed aseptic swelling Xmonths after hcrnimundibular reconsuu ction-« sequestrum of homologous bone dcbridcd-e-paticnt did well.

lIody defects

6

37 ( IX-5X)

Split rihs (n = 4). ilium (n = 2). (both had particulate autologous bone

Bone screws/wires (n = 6)

grafts)

F:Il';al bone augmcntution for contou r correcti on

Zygomatil' deprcssion Mandibular asymmetry

Reconstruction of maxillary tumor defects Maxillary umcloblustomu & giant cell grunuluma

3

IX. 21. & 39

Tibia (n = 2). femur (n = I)

Zygomaticomalar

Lag screws

eminence

2

19& 31

Femur (both)

Mandibular angle (n = I). mandibular angle + body tn = I)

Lag screws

2

19& 26

Rib crib + autologous cancellous (both)

l lcmirnuxillcctomy defects

Lag screws + hone plates

A bb revia tio ns: Orb Fl. o rbi ta l floor: A nI Max. a n terio r m a xilla.

-'" -'"

co

c.J

1184

HOMOLOGOUS BONE IN MAXILLOFACIAL SURGERY

diseases, infections or sepsis, cancer, and chronic illnesses. Serologic testing is performed on blood samples from each donor for the required tests (hepatitis B surface antigen, human immunodeficiency virus antibody [HIV Ab], hepatitis [B] core virus Ab, and serologic test for syphilis). In addition HIV 2 Ab and human Tcell lymphotropic virus I are included in the donor evaluation protoco\' Cultures are taken for aerobic and anaerobic microbial isolation. All tissues are procured following a standard surgical preparation using sterile techniques and instruments. Processing is accomplished in laminar flow hoods or using aseptic precautions as appropriate to tissue requirements. The bone available from this bone bank is not freeze-dried . Once procured, the bone is cleaned with pyrogen-free deionized water and defatted in three washes of 10%sodium hypochlorite, followed by three washes with absolute ethyl alcohol. Each wash is followed by three rinses in pyrogen-free deionized water. The bone is air-dried and sterilized by exposure to cobalt-irradiation. Control testing is performed for residual microbes following graft preparation, prior to sterilization procedures, as well as on similarly treated quality control samples following sterilization.

Results In the 3.5-year period , 135 patients received homologous bone grafts. The types of surgery for which bone grafting was performed are presented in Table I. In descending order of frequency they were acute midfacial fracture repair (n = 77), elective osteotomies of the facial bones (n = 35), secondary correction oftraumatic deformities (n = 6), mandibular reconstruction (n = 10), facial bone augmentation (n = 5), and reconstruction of maxillary tumor defects (n = 2). Postsurgical complications occurred in five of the patients. Two ofthe complications were exposure and/ or sequestration of bone grafts placed along the anterior

maxilla . This was a minor complications that required minimal care in the outpatient setting and led to no untoward sequelae . One patient who had vertical midface augmentation with homologous bone developed fibrous union and slight mobility of the maxilla. This occurred in spite of the use of plate and screw fixation. The patient subsequently underwent autogenous bone grafting with plate and screw fixation. Two pat ients who underwent mandibular reconstruction using a homologous bone graft packed with autogenous cancellous bone developed problems that required subsequent surgery under general anesthesia. One was a 15-year-old boy who underwent mandibular reconstruction 8 weeks after resection of half of his mandible for an aggressive fibrous tumor. Eight weeks later the patient developed swelling and an extraoral sinus tract. Oral antibiotics caused a resolution of the process for approximately 2 months. The patient then returned with :'similar findings and radiographic examination showed some dissolution of the bon e graft. A sequestrectomy of a portion of the composite graft was performed under general anesthesia, leaving the patient with continuity of the mandible. The second patient was a 26-year-old woman \vho underwent delayed reconstruction of the mandibular ramus and posterior body of the mandible after resection of an ameloblastoma. She did well for 8 months and returned with a nontender swelIing over the mandibular angle. A radiograph showed what appeared to be a sequestrum from the homologous bone crib. This was removed under general anesthesia and the patient did very well thereafter. MIDFACIAL TRAUMA

The most common application of homologous bone grafting was in the primary management of midfacial fractures (n = 77). In these instances, bone was used to reconstruct osseous anatomy. The most common

FIGURE I. Use of homologous split rib to fillan anterior maxillary defect following reduction and fixation of'a zygomaticomaxillary complex fracture. A. Fracture reduced and stabilized with bone plates. Note the large anterior maxillary defect. IJ. Rib contoured to bridge defect and secured with two lag screws. Note notch for infraorbital nerve.

1185

ELLIS AND SINN

raft was split rib, which can be readily curved and shape of the miss~ng anatomy. Fig~re I shows the use of homologous nb for reconstruction of the anterior maxilla following reduction and fixation of a fractured zygomaticomaxillary complex. Should reconstruction of the infraorbital rim be necessary, homologous fibula was found to be very useful. The bone is triangular in form and, when split , provides a nice contour for this purpose. It is dense cortical bone and readily accepts the application of plate and screw fixation devices without splintering. A severe orbital fracture that was reconstructed with homologous fibula and rib is demonstrated in Figure 2.

~dapted to the

MIDFACIAL OSTEOTOMIES

Homologous bone was used in 26 elective midfacial osteotomies. Most commonly, the bone was used to fill the defect in Le Fort I maxillary advancements. Although many surgeons ad vocate high Le Fort I procedures for individuals with hypoplastic maxillae, we have been dissatisfied with the problem of palpability of the bone plate along the piriform aperture after this operation. The intent of a high Le Fort I osteotomy is to augment the contours in the perinasal and infraorbital areas. Unfortunately, the higher position of the bone plate along the piriform aperture has necessitated removal in several instances due to patient complaints of palpability. An alternate technique is to perform a standard Le Fort I osteotomy where the bone cut is made as high as necessary to accommodate the position of tooth roots. Once the maxilla has been advanced (and/or inferiorly repositioned), the bone plates are applied. Cortical blocks of fibula, tibia, or femur are then contoured to the anterior surface of the maxilla above the osteotomy (Fig 3). The bone graft can extend from the advanced alveolar segment to the infraorbital rim, placing a notch for the infraorbital nerve, if indicated. The graft is frequently triangular in cross-section, being thicker at the base than at the infraorbital rim . The graft extends to and under the piriform aperture ifperinasal augmentation is desired. The source of graft depends on how much augmentation is desired . Femur has cortices from 5 to 8 mm, tibia from 4 to 6 mm , and fibula from 2 to 4 mm in thickness. The graft is placed directly over the bone plates, removing interferences along the inner surface ofthe grafts to allow proper seating on the anterior maxilla. The graft is then secured to the anterior maxilla with one or two countersunk bone screws.

mandible and augmenting the left mandibular angle region with homologous femur. This bone is very dense and can be up to 8 mm in thickness. It was placed transorally and secured with lag screws.

Discussion Based on our experience, we believe that homologous bone has many uses in maxillofacial surgery. Similar experience has been expressed by others who have used homologous bone for filling bone cavities and cysts,5.12 the surgical repositioning of teeth, 13 alveolar ridge augmentation,10.14,15 stabilization/grafting maxillofacial osteotornies.v'""? grafting alveolar cleft defects,14.18.20 grafting nonunion of the mandible.r':" and for mandibular reconstruction.P'P The main advantage in the use of such bone is that a second donor site may be avoided, reducing morbidity and shortening the time of surgery. This is especially important in children, where large amounts ofautogenous bone may be difficult to obtain. We have used homologous bone in a number of circumstances, Most frequently, the need for a bone graft is anticipated preoperatively and patient consent is obtained for procuring autogenous and/or homologous bone. Many patients prefer homologous over autogenous bone to avoid a second surgery site. If the patient has no preference, the decision for using one over the other is usually based on the requirements ofthe defect to be reconstructed and the surgical access. If only bone grafting for facial augmentation is required, our choice is dense cortical homologous bone, usually fibula, tibia, or femur. If a coronal incision is used for surgical access, we frequently obtain cal varial grafts. Many times, however, a coronal incision is not used and homologous bone is used to preclude a second surgical site and to expedite surgery. When a bone defect is present that requires as much biologic assistance in healing as possible, a combination of homologous and autogenous cancellous bone may be chosen. For instance, in mandibular reconstruction, vertical midface augmentation, or maxillary nonunion, cancellous bone is packed around the homologous cortical bone to assist in the healing process. . Several questions about the use of homologous grafts must be addressed, however. First, what, if any, immunologic reaction does this bone cause in the host? Second, how do such grafts heal, ie, what is their ultimate fate? Third, what is the risk of transmission of disease?

FACIAL BONE AUGM ENTATION THE IMMUNE RESPONSE TO HOMOLOGOUS BONE

Dense cortical blocks are useful to augment the contour of the facial skeleton in selected cases. Figure 4 demonstrates such a case. This patient had been treated for a malocclusion with bimaxillary osteotomies and was left with a facial asymmetry. The deformity was treated by shaving the buccal cortical plate of the right

Because of the immunologic rejection oftransplants between individuals or between species,23.26 methods have been used to diminish the response to bone transplants by altering their antigenicity so that immune response of the host will not be stimulated. Several

1186

HOMOLOGOUS BONE IN MAXILLOFACIAL SURGERY

FIGURE 2. Use of homologous fibula and rib to reconstruct a severe orbital defect. A. The patient was struck in the left infraorbital area with a hammer. A 3-cm laceration in infraorbital area is present. B. Computed tomogram showing comminution of orbital rim and displacement of bone and globe. C. Defect of inferior orbital rim and orbital floor following reconstruction of lateral orbital rim with bone plates. Note the infraorbital nerve spanning the defect. Surgical access was via the laceration. D. Cross-section of homologous fibula used to reconstruct infraorbital rim. Note the suitability of this bone when cut as demonstrated. The piece of bone with the arrow is removed, leaving a bone flange for the anterior maxilla/infraorbital rim, and one for the anterior floor of the orbit. (Fig 2 continued next page.)

methods of treatment have been used, including boiling, deproteinizing, merthiolating, freezing, freezedrying, irradiating, and dry-heating the bone graft. Newer methods of assay for humoral and cell-mediated immunity have been used to determine whether implantation of bone homografts stimulates the host's immune system. 26-31 One of the most important aspects of these contemporary methods has been the recognition that bone represents a composite tissue with a variety of cell types and ground substances. Although the most significant source of antigens in bone homografts appears to be the cells bearing cell-surface antigens (HLA in humans),32-3~ there is now evidence

that certain of the components of the matrix also may be capable of evoking an immune response. 35-37 Subcellular particles in bone representing DNA-like protein have been shown to have the capacity to elicit an immune response." Freezing and freeze-drying procedures appear to destroy these subcellular particles as well as to destroy cell viability, thereby decreasing the tissue immunizing capacity of the preserved bone and leaving the matrix intact for transplantation.Pr'? Other treatments may have the same capacity for reducing the immunogenicity of the graft, but may destroy properties deemed desirable in the graft. Reports of the immunogenicity of human bone ho-

ELLIS AND SINN

1187

FIGURE 2 (COllI 'd). E. Fibula following contouring. Note the conical flanges which extend laterally and medially to accept screws to stable orbital rims. The orbital floor plate was contoured to fit on top of the fibula. F. Reconstructed rim in place. The fibula was secured to the lateral and medial orbital rims with lag screws. The orbital floor plate was secured to the fibula with screws. Homologous rib grafts were placed on top of the orbital floor plate and along the anterior maxilla . Note the notch for the infraorbital nerve. G, Radiograph of patient following surgery. II. Frontal appearance of patient 18 months after the injury,

mografts are sparse. 4 1-44 Despite the fact that many thousands of such grafts have been implanted in humans, little is known about whether there are immune responses in patients directed against bone graft-related antigens and, if so, what the nature and consequences of those responses may be. Friedlaender and coworkers evaluated human recipients of freeze-dried bone homografts for donor-specific anti-HLA antibodies to determine if clinically significant immune reactions occur. 45 Freeze-dried bone homografts from donors of known tissue type evoked donor-specific anti-Hl.A antibodies in nine of their 43 patients. Eight of the nine sensitized patients were followed radiographically for

an average of23 months and were known to have had a satisfactory resolution of the benign process for which the graft was used. The ninth patient was doing well when lost to follow-up 4 month after receiving the graft. The results of this study indicate that freeze-drying may leave some antigens intact but the clinical significance of this is thought to be negligible. HEALING OF HOMOLOGOUS BONE GRAFTS

Of some importance to the clinician is the ultimate fate of homologous bone grafts. Are they replaced in time by host bone? Do they resorb and leave nothing

1188

HOMOLOGOUS BONE IN MAXILLOFACIAL SURGERY

FiGURE 3. "A . Illustration showing the location of the plate along the piriform aperture when used in high Le Fort I osteotomies to advance the maxilla. This plate is frequently palpable (arrol\') following surgery. An alternative technique is demonstrated in Band C. where a standard Le Fort I osteotomy is performed and bon e plates applied. Homologous cortical bone grafts are then contoured and placed over the top of the bone plate(s) to provide contour augmentation and facilitate healing.

behind? Do they resorb and leave fibrous tissue remaining? Do they remain as inert "implants" surrounded by host bone and/or fibrous tissue? Most studies in the literature have shown that homologous grafts are more or less completely incorporated by the host and become impossible to distinguish from an autogenous transplant.46-50 However, the result depends on the type of bone graft placed and the characteristics of the recipient site. Initially, homologous bone grafts were thought to heal by the process of osteoconduction, a passive process where capillaries and osteoprogenitor (mesenchymal) cells from the recipient site grow into the grafted bone. The homologous graft essentially acts as a scaffold for deposition of new bone by the host bed. This leads to a slow process of "creeping substitution" of the bone graft. Later, the discovery of the process of bone induction called attention to the fact that bone is one of the few organs in the human body that retains the primordial capacity to induce regeneration of lost parts. It is now believed that the organic matrix of the bone graft contains an inductive substance and that its contact with host tissue transforms progenitor cells to become chondroblasts or osteoblasts. Thus, a homologous bone graft may be both osteoconductive and osteoinductive. What is unclear, however, is how much osteoinductive material is present is homologous grafts

prepared by different means. While freeze-drying is thought to preserve all bone morphogenetic proteins, boiling or chemically treating the graft to kill the cells and reduce antigenicity has been shown to destroy any inductive effect, perhaps by denaturing bone morphogenetic proteins within the bone,,·51-53 Further, boiling, drying, or chemically treating bone frequently causes organic elements to become coagulated, making their removal by cellular processes within the host difficult:H,54 Irradiation of bone has been used as both a sterilizing process and as a means of destroying the antigens contained within the bone. 28.33,55-57 However, the amount of radiation necessary for sterilization exceeds the amount that the bone can withstand and still induce host osteogenesis.l -" The bone used in our series, since it is treated with ethylene-oxide or radiation, probably contains little bone morphogenetic substances of any value. Several studies have suggested that the fate of homologous bone is similar to any nonviable osseous tissue and greatly parallels the fate of solid autogenous cortical block grafts;59.60 that is, the nonviable osteons must first be penetrated by a revascularization process. Small blood vessels and perivascular connective tissue cells grow into autogenous grafts within I to 2 weeks, but it takes much longer with homologous bone. 48.61-63 After the grafts are vascularized by the host,

ELLIS AND SINN

1189

FIGURE 4. Use of homologous femur to augment facial skeleton to treat asymmetry. A. Patient following bimaxiIlary osteotomies for facial asymmetry with residual asymmetry. Note the fullness of right mandible in relation to the left mandible. B. Cross-section of homologous femur . Note thickness of cortex . C. Femoral cortex after contouring for placement along mandibular an gle. D, Patient 16 months after surgery.

osteoclasts and inflammatory cells appear. The nonviable bone matrix is slowly resorbed from around the narrow central canals of each osteon. Osteogenic connective tissue cells lay down new bone on some of the surfaces of the bone trabeculae of the donor, while in other parts of the transplant the old bone tissue is simply absorbed. The dynamic process of bone resorption and bone apposition may go on until the homologous bone is totally replaced. This process of creeping substitution progresses more slowly in homografts than in fresh autografts.48.61.65 Of interest, however, is that not all the homologous bone is replaced. Studies have shown that large blocks of undecalcified cortical bone transplants

are not only slowly incorporated, but sequestered particles may be found in place as late as 20 years after the operation.V" It should not be surprising that several studies have shown that homologous bone grafts may produce less bone fill than autogenous bone grafts. Marx et al compared homologous to autogenous alveolar cleft repairs in dogs." They found that autogenous grafting provided more bone fill. That study, like many others in which autogenous and homologous bone grafts were compared, gives credence to the concept that transplanted cells arc very important in new bone formation. Stroud et al68 and Frost et al69 implanted autogenous and homologous bone interpositionally into defects

1190

HOMOLOGOUS BONE IN MAXILLOFACIAL SURGERY

created by Le Fort I osteotomy in monkeys. They found that homologous bone had less osteogenic potential than autologous bone. The homografts were more slowly revascularized than autologous grafts, but served as a scaffold for host bone deposition. It is plausible that much of the transplanted cortical bone that we used in our patients does not resorb but remains as involucra, or biocompatible "implants." This has great application for facial bone augmentation because onlay bone grafts have met with little longterm maintenance of bulk. Based on what is available in the literature, maintenance of an onlay graft can best be assured by using dense cortical bone (ie, eranial)lI,70-72 and rigidly stabilizing the graft. lI,70-75 The cortical plates of the fibula, tibia, or femur represent some of the most dense bone in the body, which should retain a large bulk when rigidly secured to the host. We have not obtained computerized tomograms on our patients, but can clearly see onlay cortical bone grafts in place on cephalograms up to 2 years after surgery. Examination of the radiographs shows little loss of bulk or contour. It is probable that these dense, rigidly fixed, cortical grafts are never completely revascularized, and much of the bone remains as an involucrum, 'acting as a homologous "implant." This should not be surprising since studies have shown that in transplantation of large blocks of cortical bone, sequestered particles may be found in place as late as 20 years after the operation.v" The fate of the bone graft also may depend on the site ofplacement. Bone grafts placed into the orbit seem to become completely incorporated and appear as normal bone months after placement. We have had to reoperate on four patients who had orbital bone grafts placed previously, and in every instance found the bone to have been completely incorporated with host bone. The periorbita could be readily stripped, revealing vascularized bone with little demarcation between the graft and host bone. However, these grafts were usually thin cortical plates, such as split ilium or rib, which may allow them to become more thoroughly incorporated than thick, dense cortical blocks used as onlays. TRANSMISSION OF INFECTIOUS DISEASES

Surgeons and patients alike, who are considering transplantation of bone homografts, are justifiably concerned about transmission of infectious diseases with the graft. Foremost among such diseases is the concern of transmitting HIV. Since the acquired immunodeficiency syndrome (AIDS) has now reached epidemic proportions, and since transmission of HIV with a bone homograft has been reported," the degree of concern has heightened. Although the fear of infection with HIV or hepatitis

is great and has received significant media attention, the small number of documented cases indicate the incidence is exceedingly rare with transplants of bone. Even prior to serologic testing of donors for specific infectious diseases, only one case of hepatitis B transmission from a bone graft had been reported, and this was from a refrigerated graft taken from an amputated specimen in 1954.77 This finding might suggest that osseous tissues do not harbor large quantities of virus. Transmission of HIV-l from bone grafts has now been reported from two donors. One case involved a femoral head homograft removed during hip surgery on a 52-year-old man in November 1984.76,78 The recipient of the bone was a woman with progressive idiopathic scoliosis who underwent fusion of a lateral curvature of the spine. The homograft obtained from the donor was acquired from the hospital bone bank and used in the procedure. Twenty months later, the recipient complained of enlarged lymph nodes. In February 1988, she tested positive for HIV antibody. On further investigation, the donor was found positive for the HIV antibody and was diagnosed as having AIDS. He later died of recurrent pneumocystis pneumonia and atypical mycobacteriosis. Of note in this case was that no HIV antibody screening of the donor was performed (prior to 1985, no serologic test for HIV antibodies was available). The second case was reported in newspapers nationally in mid-May 1991.79 This case is of more concern because transmission of HIV-1 by transplantation oforgans and tissues in several recipients occurred even though the donor was screened for HIV-1. From available information, a 22-year-old man was shot and killed during a 1985 service station robbery. He had no identified risk factors for HIV and tested negative for HIV antibodies. All four recipients of organs and all three recipients of unprocessed frozen bone were infected with HIV-1. However, 34 recipients of other tissues (two receiving corneas, three receiving lyophilized soft tissue, 25 receiving ethanol-treated bone, three receiving dura mater treated with gamma radiation, and one receiving marrow-evacuated, fresh-frozen bone) tested negative for HIV-l antibody. This is a case where the grafts were procured between the time the donor became infected and the appearance of antibodies. Approaches to prevention of disease transmission include the screening of prospective donors for risk factors and laboratory markers for HIV infection, and the inactivation of HIV in homografts through processing techniques. Screening donors for HIV is the most effective method of preventing transmission of such infection. Unfortunately, however, there is usually a period of several weeks to 6 months between HIV infection and the appearance of HIV antibody." Most infected individuals become seropositive within 2 to 3

1191

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months. The exact risk of HIV transmission from a seronegative donor, as in the one case presented above, is unknown, but is very small. More than 60,000 organs and 1 million tissue homografts have been transplanted in the United States since routine donor screening for antibody to HIV was instituted in 1985. By 1990, only one case of HIV transmission from a seronegative donor, the one discussed above , had occurred." In an excellent theoretical study using analysis of available data, Buck et al calculated that with proper precautions and adequate laboratory testing, the incidence of transmission of HIV through homologous bone transplants was less than one in a rnillion.!' There has also been a recommendation for delaying transplantation of banked tissues for several months until recipients of fresh tissues from the same donors, such as organs, can be followed to determine if they may have become infected." This would be a method of positively eliminating the potential of infecting recipients of banked tissues. Homograft processing that eliminates or inactivates HIV also may reduce the risk of HI V transmission by transplantation. The ability of heat, ethanol and other chemicals, and ultraviolet and gamma radiation to inactivate HIV in plasma has been demonstrated.F''" In the report of transmission of HIV from a seronegative donor cited above, those tissues that were processed prior to transplantation, such as bone, did not infect the recipients." However, Buck et al demonstrated that bone samples taken from AIDS patients at autopsy harbored the HIV. 85 After freezing, some initially positive specimens no longer yielded virus, but those that continued to yield virus were not further altered by subsequent washing, which removed essentially all marrow, or by freeze-drying. These findings indicate that the safeguards against potential transmission of HIV by a bone homograft are principally the screening and testing methods for donors, which include rigorous donor selection, repeated screening for HIV antibodies and antigens, and detailed morphologic tissue studies. An HIV carrier may be excluded from the donor pool for anyone ofseveral reasons. However, for an infected donor to go unrecognized, all of the combined screen- . ing methods would have to fail." Should these steps fail and an infected individual who is seronegative become a donor, there may be a further reduction in the chance of transmission of HI V by the processing steps in the usual technical sequence for tissue banking. Thus, the use of bone homografts poses an added risk, albeit slight, to both the patient and surgeon. Therefore, it is important for the surgeon to be familiar with the guidelines for specimen collection used by tissue banks for harvesting from cadaver donors. The decision to use homograft for patient treatment rests with the surgeon and patient. The surgeon must have con-

fidence in the source of the homograft, which requires a working knowledge of how the tissue bank operates. Patients must be educated to make an informed choice between homograft and other treatment options.

References I. Urist MR: Surface-decalcified allogeneic bone implants. Clin Orthop 56:37, 1968 . 2. Burchardt H, Busbee GA, Enneking WF: Repair of experimental autologous grafts of cortical bone. J Bone Joint Surg 57A: 814, 1975 3. Burchardt H, Glowczewskie FP, Enneking WF: Allogenic segmental fibular transplants in azathioprine-immunosuppressed dogs. J Bone Joint Surg 59A:881, 1977 4. Burchardt H, Jones H, Glowczewskie F, et al: Freeze-dried allogeneic segmental cortical-bone grafts in dogs. J Bone Joint Surg 60A:1082, 1978 5. Boyne PJ: Treatment of extravasation cysts with freeze-dried homogenous bone grafts. J Oral Surg 14:206, 1956 6. Constantinides J, Zachariades N: Homogenous bone grafts to the mandible. J Oral Surg 36:599, 1978 7. Cooksey DE: Clinical and animal experiments to investigate the healing properties of freeze-dried bone materials in cysts of the jaws. Thesis, Graduate School of Georgetown University, Washington, DC, 1954 8. Kaban LB, Mulliken JB, Glowacki J: Treatment ofjaw defects with demineralized bone implants. J Oral Maxillofac Surg 40: 623, 1982 9. Marble HB: Hornografts of freeze-dried bone in cystic defects of the jaws. Oral Surg 26: 118, 1968 10. Marx RE, Kline SN, Johnson RP, et al: The use of freeze-dried allogeneic bone in oral and maxillofacial surgery. J Oral Surg 39:264, 1981 II. Richter M, Laurent F, Chausse JM: Homologous cancellous bone grafts for large jaw defects caused by bone cysts. J Oral MaxiIIofac Surg 44:447, 1986 12. Spcngos MN: Irradiated allogeneic bone grafts in the treatment of odontogenic cysts. J Oral Surg 32:674, 1974 13. Boyne PJ: Use of freeze-dried homogenous bone grafts in the surgical positioning of teeth. J Oral Surg 15:231, 1957 14. Allard RHB. Lekkas C, Sward JGN: Autologous versus homologous bone grafting in osteotomies. secondary cleft repairs and ridge augmentations: A clinical study . Oral Surg 64:269, 1987 15. Perrott DH, Smith RA. Kaban LB: The use of fresh frozen allogenic bone for maxillary and mandibular reconstruction. Int J Oral Maxillofac Surg 21:260, 1992 16. Christian JM , Peterson U : Frozen femoral head allogeneic bone grafts for orthognathic surgery. J Oral Maxillofac Surg 40: 635, 1982 17. Epker BN, Friedlaender G, Wolford LM, et al: The use of freezedried bone in the middle third face advancements. Oral Surg 42:278. 1976 18. Backdahl M, Nordin KE: Replacement of the maxillary bone defect in cleft palate. A new procedure. Acta Chir Scand 122: 131.1961 19. Kaban LB. Glowacki J: Induced osteogenesis in the repair of experimental mandibular defects in rats. J Dent Res 60: 1356, 1981 20. Nique T, Fonseca RJ. Upton LG. et al: Particulate allogeneic bone grafts into maxillary alveolar clefts in humans: A preliminary report . J Oral Maxillofac Surg 45:386. 1987 21. Shira RB, Frank OM: Treatment of nonunion of mandibular fractures by intraoral insertion of homogenous bone chips. J Oral Surg 13:306, 1955 22. Marx RE, Saunders TR : Reconstruction and rehabilitation of cancer patients, ill Fonseca RJ, Davis WH (eds): Reconstructive Preprosthetic Oral and Maxillofacial Surgery. Philadelphia. PA, Saunders, 1986, Chapter 9, pp 347-426

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49. Weaver JB: Experiences in the use of homogenous (bone bank) bone. J Bone Joint Surg 31:778, 1949 50. Wilson PD: Experience with the use of refrigerated homogenous bone. J Bone Joint Surg 33B:301, 1951 51. Deleu J, Trueta J: Vascularization of bone grafts in the anterior chamber of the eye. J Bone Joint Surg 47B:319, 1965 52. Keith WS: Small bone grafts. J Bone Joint Surg 16:314, 1934 53. Williams G: Experiences with boiled cadaveric cancellous bone for fractures oflong bones. J Bone Joint Surg 46B:398, 1964 54. Wilson PD: Experiences with a bone bank. Ann Surg 126:932, 1947 55. Bassett CAL, Packard AG: A clinical assay of cathode ray sterilized cadaver bone grafts. Acta Orthop Scand 28:198, 1959 56. Manning CW: A bone bank. Proc R Soc Med 53:935, 1960 57. Urist MR, Mikulski AJ, Boyd SD: A chemosterilized antigen extracted bone morphogenetic alloimplant. Arch Surg 110: 416, 1975 58. Urist MR: Practical applications of basic research on bone graft physiology, ill Instructional Course Lectures, The American Academy of Orthopedic Surgery, vol 25. St Louis, MO, Mosby, 1976 59. Burwell RG: The fate of freeze dried bone allograft. Transplant Proc 8:95, 1976 (suppl I) 60. Enneking WF, Burchardt H, Puhl 11, et al: Physical and biological aspects of repair in dog cortical bone transplants. J Bone Joint Surg 57A:232, 1975 61. Burwell RG: The fate of bone grafts, ill Apley AG (ed): Recent Advances in Orthopedics. London, England, Churchill, 1969, pp 115-207 . 62. Peer LA: Transplantation ofTissues, vol I. Cartilage, Bone; Fascia, Tendon, and Muscle. Baltimore, MD, Williams & Wilkins, 1955, pp 152-153 63. Turner TC, Bassett CAL, Pate JW, et al: An experimental cornparison of freeze-dried and frozen cortical bone-graft healing. J Bone Joint Surg 37A:1197, 1955 64. FriedlaenderGE, Mankin HJ, Sell KW: Osteochondral Allografts: Biology, Banking, and Clinical Applications. Boston, MA, Little, Brown, 1983 65. Kreuz FP, Hyatt GW, Turner TC, et al: The preservation and clinical use of freeze-dried bone. J Bone Joint Surg 33A:863, 1951 66. Wilson PD: A clinical study of the biomechanical behavior of massive bone transplants used to reconstruct large bone defects. C1in Orthop 87:81, 1972 67. Marx RE, Miller RI, Ehler WJ, et al: A comparison of particulate allogeneic and particulate autogenous bone grafts into maxillary alveolar clefts in dogs. J Oral Maxillofac Surg 42:3, 1984 68. Stroud SW, Fonseca RJ, Sanders GW, et al: Healing of interpositional autologous bone grafts after total maxillary osteotomy. J Oral Surg 38:878, 1980 69. Frost DE, Fonseca RJ, Burkes EJ: Healing of interpositional allogeneic lyophilized bone grafts following total maxillary osteotomy. J Oral Maxillofac Surg 40:776, 1982 70. Peer L: The fate of autogenous human bone grafts. Br J Plast Surg 3:233, 1950 71. Wilkes GH, Kernahan DA, Christenson M: The long-term survival of onlay bone grafts: A comparative study in mature and immature animals. Ann Plast Surg 15:374, 1985 72. Zins JE, Whitaker LA: Membranous versus endochondral bone: Implications for craniofacial reconstruction. Plast Reconstr Surg 72:778, 1983 73. Beckers HL, Frietag V: Fixation of onlay bone grafts with lag screws. J Maxillofac Surg 8:316, 1980 74. Conley J: Use of composite flaps containing bone for major reo pairs in the head and neck. Plast Reconstr Surg 49:522, 1972 75. La Trenta GS, McCarthy JG, Cutting CB: The growth of vascularized bone transfers. Ann Plast Surg 18:511, 1987 76. Transmission of HI V through bone transplantation: Case report and public health recommendations. MMWR 37:597, 1988 77. Shutkin NM: Homologous-serum hepatitis following the use of refrigerated bone bank bone. J Bone Joint Surg 36A: 160, 1954 78. Center for Biologics and Research: Revised recommendations for prevention of human immunodeficiency virus (HlV)

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1193 82. Hilfenhaus JW, Gregersen JP, Mehdi S, et al: Inactivation of HIV-l and HIV-2 by various manufacturing procedures for human plasma proteins. Cancer Detect Prcv 14:369, 1990 83. Kitchen AD, Mann GF, Harrison JF, et al: Effect of gamma irradiation on the human immunodeficiency virus and human coagulation proteins. Vox Sang 56:223, 1989 84. Wells MA, Wittek AE, Epstein JS, et al: Inactivation and partition of human T-celllymphotrophic virus, type Ill, during ethanol fractionation of plasma. Transfusion 26:210, 1986 85. Buck BE, Resnick L, Shah SM, et al: Human immunodeficiency virus cultured from bone. Implications for transplantation. C1in Orthop 251:249, 1990