The biology of bone grafting.

Allograft bone continues to play an important role in revision hip and knee arthroplasty with well documented clinical success. A basic understanding of allograft biology and immunology is important in order to optimize outcome. The importance of the interaction of immunologic factors with the biologic processes involved in bone graft incorporation has yet to be fully understood. A better understanding may, in the future, enable an improvement in the quality and uniformity of clinical outcome.

Biology of allografting.

Allograft bone continues to play an important role in revision hip and knee arthroplasty. A basic understanding of allograft biology and immunology is important in order to increase the success of allografting. Although the literature has a wealth of knowledge on the subject there are still many unknowns. The role of immunology in bone transplantation has been known for a long time, but only recently has it become apparent that the bone remodeling system and the immunologic system interact to affect the clinical success of bone transplantation. Neither of these two systems are completely understood nor is their interaction. Future research in the field of bone transplantation will be aimed at a better understanding of these systems individually but, more important, how they interact in humans. Until that time, allografting still can be used with success if one understands the role of allograft biology, immunology, and the important role of the host environment in bone transplantation.

The immune response: the afferent arm.

The key to understanding afferent immunity is the mechanism of activation of T lymphocytes by specialized antigen presenting cells, which bind antigenic peptide to Class II major histocompatibility molecules, and stimulate T cells via Signal 1 (antigen) and Signal 2 (costimulation). The best studied costimulatory pathway is the interaction of B7-1 or B7-2 ligand molecules on antigen presenting cells with CD28 or CTLA-4 receptors on T cells. T cell signaling occurs through the T cell receptor-CD3 complex and is augmented by cosignaling via CD4, CD8, and CD45. The activation of T cells to alloantigen occurs by either a direct pathway of recognition of allogenic major histocompatibility molecules (with or without an associated endogenous peptide), or by an indirect pathway of recognition of processed donor alloantigens via recipient antigen presenting cells. Afferent immunity on the musculoskeletal system is of special interest because of the absence of viable donor antigen presenting cells in processed grafts that makes them susceptible to the indirect pathway of alloantigen recognition.

Fresh osteochondral allografts for advanced giant cell tumors at the knee.

Sixteen patients with advanced giant cell tumors presenting at the knee were treated with complete tumor resection and reconstruction using fresh osteochondral allografts. All patients had one or more of the following indications for tumor resection (as opposed to curettage): tumor recurrence, pathologic fracture, or destruction of the subchondral bone plate. At the 3-15-year follow-up period (mean, 9 years), two grafts have been revised to second fresh grafts because of fracture and one graft has been converted to an allograft-implant composite reconstruction. One joint was fused because of late infection. Functional assessment was carried out in 13 patients, and 8 were good or excellent, 4 were fair, and 1 was poor. The authors conclude that the fresh osteochondral allograft is a viable treatment alternative to prosthetic arthroplasty in advanced, benign, aggressive bone tumors.

[Fresh osteochondral transplants in the treatment of advanced giant cell tumors]. / Frische osteochondrale Transplantate in der Behandlung fortgeschrittener Riesenzelltumore.

Eighteen patients with advanced giant cell tumors were treated with complete tumor resection and reconstruction using fresh osteochondral allografts. All patients had one or more of the following indications for tumor resection (as opposed to curettage): tumor recurrence, pathological fracture, or destruction of the subchondral bone plate. At the 4- to 16-year follow-up (mean 9 years), two grafts were revised to a second fresh graft because of fracture, one graft was converted to an allograft implant composite and two joints were fused because of infection. The functional results were assessed in 14 patients: 9 were good or excellent, 4 fair and 1 poor. We conclude that the fresh osteochondral allograft is a viable treatment alternative to prosthetic replacement in advanced benign, aggressive bone tumors.

Fractures following limb-salvage surgery and adjuvant irradiation for soft-tissue sarcoma.

In a prospective study, consecutive patients were treated for soft-tissue sarcoma (STS) by wide resection and adjuvant irradiation. Twelve patients had resection of bone to achieve a tumor free margin; five of these patients were left with lower extremity open segmental cortical defects in the high-dose radiation field. Four of the five patients with cortical defects suffered a fracture through the defect more than six months after surgery. Only one of 71 patients not treated with bony resection suffered a late fracture. Patients requiring bony cortex resection for STS of the lower extremity should be considered at risk for late fracture if adjuvant irradiation is prescribed.

Wound healing complications in soft tissue sarcoma management: comparison of three treatment protocols.

A prospective, nonrandomized comparison of three treatment protocols was undertaken in 45 patients with soft tissue sarcoma designated preoperatively as being at high risk of wound healing complications. All patients underwent complete resection of the gross tumour mass (5 with positive and 40 with negative microscopic margins). Fourteen patients received postoperative adjuvant irradiation (group I), 16 preoperative irradiation (group II), and 15 preoperative irradiation and vascularized tissue transfer to the surgical bed after resection (group III). Major wound healing complications (defined as complications requiring at least 1 further surgical procedure) were lower in group III patients (chi-square = 5.57, P less than 0.03), as was the mean postoperative hospital stay (P less than 0.02, analysis of variance), and the mean number of secondary surgical procedures. Multivariate analysis showed that the only variable influencing length of stay was the use of tissue transfer. Careful intraoperative assessment of the adequacy of resection is essential prior to performing vascularized tissue transfer to ensure that tumour contamination of the donor site is avoided. Since this study is a nonrandomized clinical trial using sequential distribution of patients to the treatment groups, the data should be considered as preliminary, rather than definitive, evidence of the efficacy of vascularized tissue transfer.

Analysis of alterations in the retinoblastoma gene and tumor grade in bone and soft-tissue sarcomas.

We examined 43 sporadic bone and soft-tissue sarcomas for molecular genetic alterations affecting the retinoblastoma susceptibility gene Rb-1 (also known as RB1). The gene was altered in 6 of 14 sporadic osteosarcomas and in 5 of 29 other bone and soft-tissue sarcomas. Rb-1 messenger RNA (mRNA) transcripts were detected in normal tissues and benign lipomas, but they were absent or altered in each of the 19 sarcomas we examined. To examine the association of deletions in the Rb-1 gene with tumor grade, we correlated the DNA alterations in the Rb-1 gene with clinical data for 36 patients. The Rb-1 gene was altered in 40% of high-grade bone and soft-tissue tumors, but not in low-grade bone tumors and in only one low-grade, soft-tissue sarcoma. Overall, 10 of 25 high-grade sarcomas had detectable alterations of the Rb-1 gene compared with only 1 of 11 low-grade tumors.

Class I (H-2Kb) gene transfection reduces susceptibility of YAC-1 lymphoma targets to natural killer cells.

A "hybrid gene" (MTKb) comprised of the human metallothionein IIA promoter ligated to the genomic sequence of the major histocompatibility complex class I (H-2Kb) gene was subcloned into the expression vector pSV2neo and transfected into the natural killer (NK) cell-sensitive YAC-1 lymphoma. The Kb gene product was readily detectable on the cell surface of G418-resistant transfectants using both Kb-specific monoclonal antibodies and H-2b-specific cytolytic T cells. Unlike control pSV2neo transfectants, MTKb-pSV2neo transfectants were relatively resistant to lysis by NK cells from H-2a, H-2b, H-2k or H-2 (a x b)F1 haplotype mice. These data strongly suggest that the effects of MHC expression on susceptibility to NK cells can be mediated by a single and well-defined class I molecule, Kb.

The viability of articular cartilage in fresh osteochondral allografts after clinical transplantation.

The articular cartilage of four fresh osteochondral allografts was biopsied after transplantation, and its viability was studied by autoradiography. The biopsy specimens were labeled with both 3H-cytidine, for newly synthesized ribonucleic acid, and 35S-sulphate, for newly synthesized proteoglycans. The cartilage of a lateral humeral condylar graft at twelve months had 96 to 99 per cent labeled chondrocytes, the articular cartilage of a medial femoral condylar graft at twenty-four months showed 69 to 78 per cent labeled chondrocytes, and the cartilage of a medial tibial-plateau graft at forty-one months had 90 per cent labeled cells. At six years, a lateral tibial-plateau graft had 37 per cent labeled chondrocytes.

Allograft-implant composite reconstruction following periacetabular sarcoma resection.

Ten patients with primary periacetabular sarcomas were treated with internal hemipelvectomy and allograft-implant composite reconstruction. Three patients developed local recurrences, one of which was salvaged with repeat resection. One patient underwent hemipelvectomy for infected wound recurrence. At a mean follow-up period of 25 months (range, 7-85 months; median, 18 months), six of nine patients assessed with the Musculoskeletal Tumor Society functional assessment had satisfactory results, with scores of 21 or better (of a possible 35). Although complications were frequent and functional scores were often limited by the muscle resection required for adequate tumor removal, we remain cautiously optimistic about the early results of this procedure.

Granulocyte precursors are the principal cells in bone marrow that stimulate allospecific cytolytic T-lymphocyte responses.

Mouse bone marrow cells were fractionated and enriched for functional activity as stimulators of allospecific cytolytic T-lymphocyte (CTL) responses in vitro. The relevant stimulator cells were enriched sequentially in the low-density fraction of bone marrow, its 2-hr adherent and 18-hr non-adherent fractions and in the FcR-negative fraction of 18-hr non-adherent cells. The functionally enriched cell population contained over 90% granulocyte precursors by ultrastructural analysis. The results indicate that granulocyte precursors are the principal cells in bone marrow that stimulate alloreactive T-cell responses.

Measurement of grip strength in the diagnosis of wrist pain.

Grip strength was assessed in patients with chronic wrist pain and correlated with the results of subsequent bone scans and pathology. The results showed a highly significant decrease of grip strength in patients with positive bone scans or confirmed wrist pathology compared with those with negative bone scans (p less than 0.01). We conclude that the detection of weakness of grip is a simple indicator of true pathology in "obscure" wrist pain.

Bone banks and allografts in community practice.

The increasing volume of orthopaedic reconstructive procedures requiring replacement of bone stock justifies the initiation of programs of bone banking in community hospitals. Provided that strict criteria are followed to assure rigorous screening of donor bone and the reliable preservation of bone graft material, community banking is safe and cost-effective. Banked allograft bone can be used successfully in a wide variety of orthopaedic procedures performed in community hospitals. In general, the best uses are filling bone cavities, buttressing, and augmenting the quantity of autograft bone. In revision reconstructive surgery of the hip, bank bone is used to replace bone stock in protrusio, acetabular dysplasia, and proximal femoral deficiency. The best and most common indication for the use of bank bone in tumor surgery is after curettage or excision of benign lesions. Allografts may be used to reconstruct bony defects after excision of malignant tumors and in the surgical treatment of metastatic disease. These instances require larger bone bank facilities than those commonly available in a community hospital setting. Medicolegal considerations related to bone banking and the use of allografts in community practice include the regulatory requirements outlined in the UAGA, questions concerning negligence liability, and theories of strict product liability. Overall, good medical practice and obtaining informed consents will minimize legal risks related to bone banking and transplantation in a community setting.

Ender nailing in fractures of the proximal femur.

Seven hundred twenty-three consecutive patients with intertrochanteric fractures of the femur have been treated by intramedullary nailing with Ender's nails. Six hundred forty-four patients have survived for 6 months or longer, with one patient requiring secondary surgery for delayed union and six patients requiring revision of the fixation device. The morbidity has been low, the complication rate acceptable, and the complications readily corrected. The overall result in terms of fracture healing, maintenance reduction, and functional activity has been very satisfactory.

Ulnar variance in carpal instability.

Ulnar variance was measured in wrist conditions of patients with carpal instability and compared to values obtained from the assessment of normal wrist x-ray films. The results showed a significantly greater amount of negative ulnar variance in patients with scapholunate dissociations than in normal controls (t-test, p less than 0.0005; chi-square test, p less than 0.02). Ulnar variance in lunotriquetral dissociations and old scapholunate dissociations with arthrosis did not differ significantly from controls (p greater than 0.6). Posttraumatic scapholunate dissociations do correlate with negative ulnar variance.