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.

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 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.

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.

[Fresh osteochondral transplants in the treatment of advanced giant cell tumors].

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.

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.

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).

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.

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.

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.

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.

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.

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).

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.

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.

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.

Ontogeny of priming of cytotoxic T cells to minor alloantigens: the development of direct priming precedes that of cross-priming.

Cytotoxic T lymphocytes of heterozygous adult mice primed in vivo with minor alloantigens on cells of one parental H-2 genotype can be boosted in vitro to respond to minor alloantigens on cells of both the immunizing parental H-2 genotype (direct priming) and of the H-2 genotype of the other parent (cross-priming). We studied the ontogeny of this phenomenon and show that during early postnatal life the development of direct priming precedes that of cross-priming. The delayed maturation of cross-primed responses parallels the known development time sequence of functional antigen-presenting cells and provides evidence for the explanation of cross-priming in terms of antigen processing.

Bone and cartilage allotransplantation. A review of 14 years of research and clinical studies.

The authors review their experience of over 14 years in the field of osteochondral allotransplantation. Experimental studies demonstrated the immunogenicity of bone and cartilage, immunosuppression in skeletal transplantation models, and a subset of myeloid cells within bone marrow with strong immunogenic properties. Clinical results of knee joint resurfacing with fresh small-fragment osteochondral allografts have been best in posttraumatic joints.

Analysis of HLA B27 in ankylosing spondylitis with human alloreactive cytolytic T lymphocyte clones: failure to detect disease-related T cell epitopes.

We have generated several human alloreactive cytolytic T lymphocyte (CTL) clones specific for HLA B27 expressed on cells of normals or of patients with ankylosing spondylitis (AS). These clonal T cell reagents were used to test the recognition of panels of target cells from B27+AS+, B27+AS- and B27- individuals. None of these CTL clones distinguished differences between B27+AS+ and B27+AS- cells.

Antigen presenting cells and bone allotransplantation.

Antigen presenting cells may have a direct bearing on the results of allotransplantation of bone. There is no doubt that these cells are neither T nor B lymphocytes and that they do reside in the bone marrow. Evidence suggests that these bone marrow cells are of the granulocyte lineage and that they initiate immunologic reactions in vitro.