by Michael H. McGuire, MD
Michael H. McGuire, MD, is professor and chairman, department of surgery, Creighton University, Omaha, Neb.
The modern era of orthopaedics spans the 20th century. The transplantation of human cadaver allograft bones for the reconstruction of skeletal defects has been one of the highlights of the history of orthopaedic surgery during this century. An idea that was at one time surely a desperate response to a desperate problem has become a rather sophisticated system for planned reconstructions.
Since the work of Parrish and others in the 1960s, surgeons have demonstrated the ability to perform limb-sparing resections of malignant tumors of the skeleton. Most estimates suggest that approximately 2,500 new cases of primary sarcomas of the skeleton are diagnosed each year. These are osteosarcomas and Ewing's sarcomas in adolescents and chondrosarcomas and MFH/fibrosarcomas in older adults and elderly. These routinely arise from the appendicular skeleton. With early diagnosis, appropriate radiographic and MR imaging, an understanding of oncologic principles, and careful surgery, most can be treated by resection of the tumor rather than amputation of the limb. The problem then becomes one of successful reconstruction.
The history of clinical application of allograft bone transplants begins with the reports of MacEwen and Lexer from the early part of the century. A partial list of the players in this drama/act include Phemister of Chicago; Herndon and Chase of Cleveland; Ottolenghi of Buenos Aires, Argentina; Burwell of Oswestry, England; Parrish of Houston and, of course, their patients. More recently, Mankin, Friedlaender, Tomford, Gebhardt and others have worked diligently to establish and standardize the techniques for both the banking of cadaver bones and the successful clinical use of these bones.
Phemister in 1914 in an article, "The Fate of Transplanted Bone and Regenerative Power of its Various Constituents" (Surg Gynecol Obstet 1914;19:303) stated "all of the experiments were performed upon dogs with bone from the same animal, as it has been sufficiently proved that bone from a different animal of the same species behaves in the same manner as that from the same animal, but with somewhat diminished powers, and that a transplant from a different species acts the same as dead bone or any other foreign body." I agree with his assessment.
Now, more than 80 years later, we know that the transplantation of bone evokes an immune response (at least in the early postop period), and we know that that response is decreased by freezing of the bones in storage. Healing at the osteosynthesis and the gradual replacement of the graft occurs slowly by the process generally recognized as creeping substitution. No clinically significant rejection is seen and no immunosuppression regimen or drugs are used. The articular cartilage is an avascular tissue that is inert (or privileged) from an immune status. The chondrocytes have low metabolic demands and often survive the storage/freezing and regain viability when transplanted to a healthy synovial joint.
The American Association of Tissue Banks has established the standards, procedures and policies for the safe retrieval and storage of cadaver musculoskeletal tissues. Tissue banks meeting these standards can seek certification through the American Association of Tissue Banks. With careful screening of donors and with the appropriate testing of serum and other body fluids, the tissues retrieved for banking are free of risk of disease transmission. The bones and tissues are obtained in a sterile fashion and are either fresh frozen or freeze-dried. Freeze-dried tissues (such as blocks and struts of cancellous and/or cortical bone) can be secondarily sterilized prior to storage and use. Currently, I feel that it is safe to say that basically no risk of disease transmission exists in the use of allograft bones.
The skeletal defect to be replaced by the transplanted segment of bone may require either an osteoarticular graft to replace the end or an intercalary graft to replace the shaft of the long bone. The original location of the tumor and the requirements of the resection obviously dictate or define the defect.
An intercalary graft to replace the shaft of a long bone (while maintaining the joint and its surrounding structures both proximal and distal to the graft) allows the surgeon and the patient to potentially achieve a normal extremity following the resection. In this case, healing of the graft and host tissues at the osteosynthesis site accomplishes true biologic fixation of the "implant." Fixation of the allograft bone can be accomplished by either an intramedullary device or by plate and screws. Rigid fixation at the osteosynthesis site must be accomplished to encourage healing of the cortical bone of the host to that of the graft.
The replacement of the end of a long bone and half of the associated joint is accomplished by the transplantation of an osteoarticular graft. Allograft segments with joint capsules and ligaments intact make the reconstruction of a mobile joint possible. A clever and creative surgeon can repair or reconstruct the joint capsule and ligamentous structures in a most satisfactory fashion. Host muscle tendon units can be attached to the graft through normal tendon insertion sites. The fixation of the graft to the host is accomplished in a rigid fashion, most commonly using a plate and screws. Step cut osteotomies add rotational control and extend the surface area at the graft site. With a successful outcome, a nearly normal joint can result.
A great example of the use of an osteoarticular graft would be for the reconstruction of a proximal humerus and shoulder following the resection of a low-grade chondrosarcoma. If the resection of the humerus can be accomplished at a level proximal to the insertion of the deltoid muscle, the allograft can function mostly as a fulcrum for the arm. By reattaching the rotator cuff tendons to the allograft, nearly normal function of the shoulder can result. The non-weightbearing status of the shoulder joint makes it likely that the articular cartilage would be sufficient for many years. Similar results can be obtained about the hip joint. A number of surgeons have found it advantageous to combine a proximal femoral allograft with a standard total hip replacement (an allograft-prosthesis composite).
In summary, when at all possible and when patient preferences allow, I favor the use of an allograft bone transplant for the reconstruction of skeletal defects following the resection of tumors. The bone, cartilage and associated connective tissues make a biologic implant. The transplant is accepted by host tissues. Healing to the host and even biologic replacement of the graft occur without clinical rejection. When complete, the transplant has reconstructed the skeleton and allows for an entire range of more standard orthopaedic procedures.