William W. Tomford

Infection in bone allografts. Incidence, nature, and treatment.

Of 283 patients who had a massive allograft of bone, an infection developed in thirty-three (11.7 per cent). To assess the frequency and identify the co-morbid and predisposing factors of this devastating complication, we compared demographic data for the infected and non-infected patients. Comparison of mean age, type of graft, anatomical site of the procedure, and stage of the tumor yielded no significant differences. Multiple-regression analysis of a subgroup of eighty-two patients who had a distal femoral graft showed a correlation between infection and factors that are associated with more extensive surgery (more loss of bone, soft tissue, or skin) or with multiple operations. Approximately 30 per cent of the patients who had an infected allograft had no co-morbid or predisposing factors that could be statistically correlated with an increased risk for infection. Gram-positive organisms were the most common cause of infection, with twelve infections (36 per cent) being due to Staphylococcus epidermidis. Six patients had a single gram-negative organism and nine had mixed flora. The final result in the thirty-three patients who had an infected allograft was poor compared with that of the over-all series and of the uninfected patients. Twenty-seven infected allografts (82 per cent) were considered to be failures of treatment because amputation of the limb or resection of the graft was required to control the infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Osteoarticular and intercalary allograft transplantation in the management of malignant tumors of bone.

Since 1971, the Orthopaedic Service at the Massachusetts General Hospital has treated 106 patients with malignant or aggressive bone tumors by wide resection and replacement with frozen cadaveric allograft. Sixty‐one of these patients have been followed for over two years (mean, 4.5 years), allowing a comprehensive end‐results analysis. In 45 patients, mostly with giant‐cell tumors or chondrosarcomas, the resection involved the articular end of a long bone and the replacement not only included bone, but glycerolized (to prevent freezing injury) articular cartilage. Ten of the segments were intercalary (bone alone) and six involved a combination of bone and a metallic joint prosthesis. Patients were graded as excellent, good, fair, or failure, depending principally on functional capacity. End‐results analysis in this group showed that five of the 61 patients had either a local recurrence (2) and/or distant metastases (3); in five additional patients the limb was amputated or the implant removed, primarily because of infection (total failure rate, 16.5%). Forty‐five (73.8%) had successful transplants (graded excellent or good) and were able to live essentially normal lives. Six of the patients (10%) required a brace or cane but three of these patients were able to return to preoperative work activities. Although the operations were arduous and difficult, and despite a high infection rate (13%) and occasional pathologic fractures (10%), the results compare favorably with other techniques used to restore the skeleton following massive segmental resection. In long‐term follow‐up, the data suggest that if no complications ensue in the first two years, the results are generally quite good and the grafts show no evidence of progressive deterioration with time.

Factors affecting nonunion of the allograft-host junction.

Nonunion of allograft-host junction after bone transplantation is not uncommon, and its treatment frequently is problematic. To improve the understanding of these nonunions, a retrospective review was performed of 163 nonunions in 945 patients who underwent allograft transplantation (17.3%) for various benign and malignant tumors at the authors’ institution between 1974 and 1997. Of these 945 patients, 558 did not receive adjuvant therapy. Chemotherapy was administered to 354 patients and only 33 patients received radiation therapy alone. Seventy-one patients had radiation treatment and chemotherapy. Of the 163 patients who had nonunion develop at the allograft-host junction, there were 269 reoperations performed on the involved extremity. In 108 patients, treatment was successful resulting in union of the allograft-host junction. Forty-nine patients did not respond to multiple surgical treatment attempts. The greater the number of surgical procedures, the worse the outcome. The rate of nonunions increased to 27% for the patients who received chemotherapy as compared with 11% for the patients who did not receive chemotherapy. The order of allografts from highest rate of nonunion to lowest was as follows: alloarthrodesis, intercalary, osteoarticular, and alloprosthesis. Infection and fracture rates were higher in the patients with nonunions as compared with the patients without nonunions.

Frozen musculoskeletal allografts. A study of the clinical incidence and causes of infection associated with their use.

A retrospective study was performed to determine the clinical incidence and causes of infection related to the use of frozen musculoskeletal allografts. The results of this study of 324 grafts, prepared and supplied by our hospital bone bank, showed that the patients in whom femoral head grafts and other small bone and soft-tissue allografts were used had a negligible clinical incidence of infection. The incidence of infection related to the use of large allografts, such as osteoarticular or diaphyseal grafts, was approximately 5 per cent in patients who had treatment for a bone tumor and 4 per cent in those who had revision of a hip arthroplasty. These rates of infection were not substantially different from those that have been reported in similar series in which large allografts or sterilized prosthetic devices were used. The causes of the infections were difficult to determine, but contamination of the allograft was probably not a factor in most patients.

A study of the clinical incidence of infection in the use of banked allograft bone.

To determine the incidence of infection in grafting procedures utilizing banked allograft bone, 567 questionnaires were sent to collaborating surgeons who used Navy Tissue Bank freeze-dried allograft bone from October 1973 to October 1976. Three hundred and three questionnaires were sufficiently completed to be included in the study. Twenty-one patients were reported as showing evidence of infection, of which twelve were considered minor and nine were considered major according to the effect on the patients postoperative course. In eleven of the twenty-one patients there were positive cultures as proof of infection: in the remaining ten there were not. Analysis of the proved infections showed that the allograft was probably not primarily responsible in most of the patients. Based on the data obtained in this study, the incidence of infection with the use of banked allogenous bone appears to compare favorably with infection rates reported for orthopaedic procedures utilizing autogenous bone.

Immunologic responses in human recipients of osseous and osteochondral allografts.

A multiinstitutional study was carried out to evaluate immunologic responses for human recipients of massive frozen (-80 °C) osseous and osteochondral allografts. Allografts were used to reconstruct skeletal defects associated with a variety of traumatic degenerative and neoplastic disorders. Serum samples were obtained before surgery and from 1 month to 4 years after surgery. Sera were tested by microcytotoxicity against T cells from 60 donors for human leukocyte antigen Class I antibodies and against β2-microglobulin treated B cells from 40 donors for human leukocyte antigen Class II antibodies. Panels were selected to represent the majority of known human leukocyte antigen specificities. Of the 84 cases evaluated, 62 (74%) received blood transfusions and 28 of 44 (64%) female recipients had been previously pregnant. Sensitization before transplant was shown in 33 of 84 (39%) patients. After grafting, 49 of 84 (58%) recipients showed evidence of sensitization to Class I antigens and 46 of 84 (55%) recipients showed evidence to sensitization to Class II antigens. Overall sensitization was 67%.

BONE BANKING: Update on Methods and Materials

Bone allografts are being used in increasing numbers by orthopedic surgeons, yet many surgeons are unfamiliar with their preparation and processing, as well as their use as safe and effective transplants. This article reviews current sources of bone allografts, new methods of processing to achieve optimal results, the biology of incorporation of allografts, and new bone substitutes.

Improved fixation of the femoral component after total hip replacement using a methacrylate intramedullary plug.

When the distal part of the medullary canal of the femur was plugged with a bolus of methylmethacrylate prior to the insertion of cement and femoral component, fixation of the prosthesis was improved in vitro. A special syringe was devised to introduce the plug at the desired level. When the plug was used, the penetration of the cement into the trabecular bone lining the canal was increased, and subsequent push-out tests showed that the force necessary to disrupt the methacrylate from the bone was significantly greater. Casts of the methacrylate from femora with and without plugged canals showed that the surfaces of the casts made with the canal plugged conformed much more completely with the irregularities of the bone and provided more intimate contact at the cement-bone interface.

LONG-TERM FOLLOW-UP OF PATIENTS WITH OSTEOCHONDRAL ALLOGRAFTS: A Correlation Between Immunologic Responses and Clinical Outcome

This article confirms immunologic responses in humans to histocompatibility antigens (Class I and II) presented by frozen osteochondral allografts. These observations include a correlation of immune responses with long-term clinical outcome. As found in animal models, matching of histocompatibility antigens, particularly to Class II, improves clinical and, presumably, biologic success following implantation of massive frozen bone allografts in humans. The presence of sensitization clearly does not preclude a satisfactory outcome, nor have other reconstructive alternatives (e.g., metallic implants) been shown to be superior in their long-term results.

Allograft fractures revisited.

A retrospective review of patients with allograft fractures was done at the authors’ institution. Between 1974 and 1998, 185 of 1046 (17.7%) structural allografts fractured in 183 patients at a mean of 3.2 years after transplantation. Initial allograft fixation included internal fixation with plates and screws in 181 patients. Patients with grafts that were longer than the average length (15.5 cm) tended to have worse results. Adjuvant therapy had no effect on fracture rate. Seventy-three patients with fractures had other allograft complications. Infection and nonunion with allograft fracture significantly worsened the outcome. The incidence of fracture in the patients with osteoarticular and arthrodesis transplants was significantly higher than those patients who had intercalary and composite reconstructions. Treatment of the allograft fractures included open reduction and internal fixation in 41 patients, reconstruction with a new allograft in 38, allograft-prosthesis composite in five, oncologic prosthesis in 19, amputation in 15, arthroscopic removal of loose bodies in three, resurfacing of fractured osteoarticular allograft surfaces in 39, allograft removal and cement spacer placement in 15. Twenty patients did not receive treatment. Eight of the fractures in patients who were not treated healed spontaneously. Outcomes were judged as excellent in nine patients (4.9%), good in 72 patients (38.9%), fair in 17 patients (9.2%), and in 85 patients (45.9%) the allograft reconstruction failed.