Intercalary Bone Allografts Research Articles

Scaffold-free Three-dimensional Graft From Autologous Adipose-derived Stem Cells for Large Bone Defect Reconstruction: Clinical Proof of Concept.

Long bone nonunion in the context of congenital pseudarthrosis or carcinologic resection (with intercalary bone allograft implantation) is one of the most challenging pathologies in pediatric orthopedics. Autologous cancellous bone remains the gold standard in this context of long bone nonunion reconstruction, but with several clinical limitations. We then assessed the feasibility and safety of human autologous scaffold-free osteogenic 3-dimensional (3D) graft (derived from autologous adipose-derived stem cells [ASCs]) to cure a bone nonunion in extreme clinical and pathophysiological conditions.Human ASCs (obtained from subcutaneous adipose tissue of 6 patients and expanded up to passage 4) were incubated in osteogenic media and supplemented with demineralized bone matrix to obtain the scaffold-free 3D osteogenic structure as confirmed in vitro by histomorphometry for osteogenesis and mineralization. The 3D “bone-like” structure was finally transplanted for 3 patients with bone tumor and 3 patients with bone pseudarthrosis (2 congenital, 1 acquired) to assess the clinical feasibility, safety, and efficacy. Although minor clones with structural aberrations (aneuploidies, such as tri or tetraploidies or clonal trisomy 7 in 6%–20% of cells) were detected in the undifferentiated ASCs at passage 4, the osteogenic differentiation significantly reduced these clonal anomalies. The final osteogenic product was stable, did not rupture with forceps manipulation, did not induce donor site morbidity, and was easily implanted directly into the bone defect. No acute (<3 mo) side effects, such as impaired wound healing, pain, inflammatory reaction, and infection, or long-term side effects, such as tumor development, were associated with the graft up to 4 years after transplantation.We report for the first time that autologous ASC can be fully differentiated into a 3D osteogenic-like implant without any scaffold. We demonstrated that this engineered tissue can safely promote osteogenesis in extreme conditions of bone nonunions with minor donor site morbidity and no oncological side effects.

Oncology

The June 2015 Oncology Roundup360 looks at: Infection in megaprosthesis; Impressive results for mid femoral reconstruction; Revered teaching or old myth? Femoral neck protection in metastatic disease; Megaprosthesis about the knee; Malignant transformation in multiple hereditary exostoses; Fracture of intercalary bone allograft; Comorbidity and outcomes in sarcoma; A worrying turn? Use of denosumab for giant cell tumour of bone

Should fractures in massive intercalary bone allografts of the lower limb be treated with ORIF or with a new allograft?

Massive bone allografts have been used for limb salvage of bone tumor resections as an alternative to endoprostheses, although they have different outcomes and risks. There is no general consensus about when to use these alternatives, but when it is possible to save the native joints after the resection of a long bone tumor, intercalary allografts offer some advantages despite complications, such as fracture. The management and outcomes of this complication deserve more study. The purposes of this study were to (1) analyze the fracture frequency in a group of patients treated with massive intercalary bone allografts of the femur and tibia; (2) compare the results of allografts treated with open reduction and internal fixation (ORIF) with those treated with resection and repeat allograft reconstruction; and (3) determine the likelihood that treatment of a fracture resulted in a healed intercalary reconstruction. We reviewed patients treated with intercalary bone allografts between 1991 and 2011. During this period, patients were generally treated with intercalary allografts when after tumor resection at least 1 cm of residual epiphysis remained to allow fixation of the osteotomy junction. To obtain a homogeneous group of patients, we excluded allograft-prosthesis composites and osteoarticular and hemicylindrical intercalary allografts from this study. We analyzed the fracture rate of 135 patients reconstructed with segmental intercalary bone allografts of the lower extremities (98 femurs and 37 tibias). In patients whose grafts fractured were treated either by internal fixation or a second allograft, ORIF generally was attempted but after early failures in femur fractures, these fractures were treated with a second allograft. Using a chart review, we ascertained the frequency of osseous union, complications, and reoperations after the treatment of fractured intercalary allografts. Followup was at a mean of 101 months (range, 24-260 months); of the original 135 patients, no patient was lost to followup. At latest followup, 19 patients (14%) had an allograft fracture (16 femurs [16%] and three tibias [8%]). Six patients were treated with internal fixation and addition of autologous graft (three femurs and three tibias) and 13 patients were treated with a second intercalary allograft (13 femurs). The three patients with femoral allograft fractures treated with internal fixation and autologous grafts failed and were treated with a second allograft, whereas those patients with tibia allograft fractures treated by the same procedure healed without secondary complications. When we analyzed the 16 patients with a second intercalary allograft (13 as primary treatment of the fracture and three as secondary treatment of the fracture), five failed (31%) and were treated with resection of the allograft and reconstructed with an endoprosthesis (four patients) or an osteoarticular allograft (one patient). Fractures of intercalary allografts of the tibia could successfully be treated with internal fixation and autologous iliac crest bone graft; however, this treatment failed when used for femur allograft fractures. Femoral fractures could be treated with resection and repeat allograft reconstruction, however, with a higher refracture frequency. The addition of a vascularized fibular graft in the second attempt should be considered. Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.

Factors affecting outcome of massive intercalary bone allografts in the treatment of tumours of the femur

We retrospectively reviewed 101 consecutive patients with 114 femoral tumours treated by massive bone allograft at our institution between 1986 and 2005. There were 49 females and 52 males with a mean age of 20 years (4 to 74). At a median follow-up of 9.3 years (2 to 19.8), 36 reconstructions (31.5%) had failed. The allograft itself failed in 27 reconstructions (24%). Mechanical complications such as delayed union, fracture and failure of fixation were studied. The most adverse factor on the outcome was the use of intramedullary nails, followed by post-operative chemotherapy, resection length > 17 cm and age > 18 years at the time of intervention. The simultaneous use of a vascularised fibular graft to protect the allograft from mechanical complications improved the outcome, but the use of intramedullary cementing was not as successful. In order to improve the strength of the reconstruction and to advance the biology of host-graft integration, we suggest avoiding the use of intramedullary nails and titanium plates, but instead using stainless steel plates, as these gave better results. The use of a supplementary vascularised fibular graft should be strongly considered in adult patients with resection > 17 cm and in those who require post-operative chemotherapy.

Incorporación de aloinjertos óseos intercalares corticales: Estudio experimental en conejos

An experimental study was carried out on 40 rabbits in order to evaluate the incorporation of large intercalary bone allografts and the influence of freezing on the bone graft. In 36 rabbits resection of 3 centimetres of diaphysis of the tibia was carried out and the defect was rebuilt with different types of bone graft: fresh autograft and frozen autograft, fresh allograft and frozen allograft; osteosynthesis was carried out with two intramedullary Kirschner needles. Monthly radiological studies were made until the sacrifice of the animals, at 2, 4 and 8 months. A densitometric, histological and diaphanisation study of the tibias was made with Spalteholz's technique. In 24 animals 25 mg/kg of oxytetracicline was administered 3 and 6 days before sacrifice, to study the velocity of bone apposition in the graft. We observed a good and excellent radiological consolidation in 80% of the grafts (99% in the autografts and 66% in the allografts). The bone density showed a fall until the 4th month due to bone reabsorption except in the group of fresh allografts. The revascularization of the allografts was slower and poorer than the autografts, but with the same vascular pattern. Bone incorporation and neoformation were greater in the autografts without significant differences with the frozen allografts. The speed of bone apposition did not change with the different types of bone graft used. Freezing facilitated and accelerated incorporation and the quantity of bone neoformation of the allografts.

Non-neoplastic causes of high signal intensity at T2-weighted MR imaging after treatment for musculoskeletal neoplasm.

The objective of this study was to describe a variety of non-neoplastic causes of high-signal-intensity areas seen on T2-weighted magnetic resonance (MR) images obtained after treatment for malignant musculoskeletal neoplasm. MR examinations obtained after treatment for malignant musculoskeletal neoplasm in 11 patients were reviewed. The examinations of these patients were selected because at least one MR study of each patient showed high-signal-intensity areas on T2-weighted images at or near the site of the original tumor. The MR imaging findings were correlated with results of biopsy in four patients, and with information from follow-up radiologic examinations and the patients' medical records in all cases, to determine the cause of the high-signal-intensity areas. Non-neoplastic entities responsible for high-signal-intensity areas included postsurgical seroma, hematoma, postradiation therapy changes, fat necrosis and seroma, surgical hemostatic packing material, intercalary bone allograft, strut bone graft, atrophic muscle, and herniated colon and bladder. Knowledge of details of the surgical procedure and the time interval since surgery or irradiation aided in accurate interpretation of the findings, but did not allow immediate biopsy to be deferred in every case. High-signal-intensity areas on T2-weighted images in patients previously treated for malignant musculoskeletal neoplasm may represent a variety of entities other than residual or recurrent neoplasm, even in the presence of a mass. The MR imaging findings should be interpreted in conjunction with details of the specific clinical circumstances to prevent misdiagnosis and unnecessary biopsy.

Experimental study on vascularized bone allografts for reconstruction of massive bone defects.

To study the healing mechanism of vascularized bone allografts under short-term as well as long-term immunosuppression with cyclosporin A, experimental vascularized intercalary bone allograft transplantation was carried out between inbred rats using the tibiofibula graft model. Bone scintigram and radiographs were used as an indicator for early detection of rejection after transplantation and bone union. In vascularized bone allografts under long-term immunosuppression with cyclosporin A, early bone union and continuous incorporation were similar to that observed in vascularized bone autograft transplantation. When administration of cyclosporin A was discontinued before completion of bone union, the graft was rejected and bone union was delayed. Apparent swelling on the operated limb associated with a decrease in bone scintigram uptake suggested the occurrence of rejection of the allograft. Vascularized bone allograft transplantation is useful for reconstruction of massive bone defects only if immunosuppressants are used and maintained at least until bone union is obtained.

Intercalary bone allografts. 23 tumor cases followed for 3 years.

From 1987 to 1991, 26 patients with malignant bone tumors (osteosarcoma, Ewing's sarcoma, chondrosarcoma and malignant fibrous histiocytoma) in the diaphysis or metaphysis of long bones have been treated by chemotherapy, radiotherapy and intercalary bone allograft replacement after resection. The mean follow-up was 3 years in 23 patients, 2 died from tumors, and 1 had an amputation because of local recurrence. Allograft incorporation in 11 metaphyseal anastomoses was excellent in all cases. In the 23 diaphyseal anastomoses there were 6 non-unions. Other complications were deep infection in 3 cases, leg length discrepancy in 2 and allograft fracture in 2. Function became satisfactory in 14 cases.

The treatment of adamantinoma of the tibia by wide resection and allograft bone transplantation.

Since 1975, nine patients who had adamantinoma of the tibia were treated by the orthopaedic oncology service of the Massachusetts General Hospital and the Children's Hospital, Boston, Massachusetts. All patients were followed for two years or more or until a relapse occurred (mean length of follow-up, 5.3 years). Five of the patients were female and four were male; their ages ranged from fourteen to fifty-six years (mean, 19.1 years). The treatment consisted of staging, wide surgical resection of the tumor, and insertion of a segment of intercalary bone allograft (eight patients) or an osteoarticular segment (one patient). All grafts were fixed with compression plates and screws. All but two of the allografts had united at both the proximal and the distal host-donor junction site by twelve months. None of the patients had a local recurrence but pulmonary metastases developed in one. Four of the patients had complications that affected the final result. The functional results were excellent in five patients, good in one, fair in one, and a failure in two. Seven of the nine patients were asymptomatic and fully functional at the time of writing; only one needed a brace to walk. On the basis of this experience we recommend wide resection and implantation of an intercalary allograft in the treatment of adamantinoma of the tibia.

Banking of Massive Osteoarticular and Intercalary Bone Allografts???12 Years?? Experience

Preparation and banking of massive osteoarticular allografts and intercalary bone allografts have been performed for the past 12 years. Careful selection of donors as well as extensive laboratory studies of the donor and the allograft have virtually eliminated the danger of transmitting disease from the donor to the recipient. The availability of a variety of allografts in the Tissue Bank allows for the selection, on an anatomic basis, of an allograft best suited for a particular recipient. The authors have supplied several hundred allografts to recipients in many institutions on the premise that excision, preparation, banking, and implantation of bone allografts constitute a clinical service. Thus, the surgeon who excises and prepares the allograft assumes a joint responsibility for the care of the recipient with the surgeon who implants the allograft. This establishes a close working relationship, which encourages frequent consultation between the parties concerned. This relationship is of particular importance in the initial evaluation of the patient and in determining which particular allograft will best serve a given patient. The experience at the authors' institution provides a model for a multiinstitutional facility that may serve as a base for discussion of the methodology involved in the excision, preparation, and storage of bone allografts. The costs associated with the operation of such a facility are not inconsiderable, but the cost of individual osteoarticular and intercalary allografts can be brought down by an increase in the efficiency of operation inherent in the processing of allografts from over 100 donors per year. During the past several years, the cost of excising and preparing intercalary allografts has been $600 per implant, while the cost for osteochondral allografts varied between $900 and $1,200. Such a large multiinstitutional facility offers the advantages of readily available allografts and quality control. However, because of the expense and complexity of operation, it may not be suitable for many medical centers.