Segmental bone replacement via patient‐specific,three‐dimensional printed bioresorbable graft substitutes and their use as templates for the culture of mesenchymal stem cells under mechanical stimulation at various frequencies

The treatment of large segmental bone defects remains a challenge as infection, delayed union, and nonunion are common postoperative complications. A three‐dimensional printed bioresorbable and physiologically load‐sustaining graft substitute was developed to mimic native bone tissue for segmental bone repair. Fabricated from polylactic acid, this graft substitute is novel as it is readily customizable to accommodate the particular size and location of the segmental bone of the patient to be replaced. Inspired by the structure of the native bone tissue, the graft substitute exhibits a gradient in porosity and pore size in the radial direction and exhibit mechanical properties similar to those of the native bone tissue. The graft substitute can serve as a template for tissue constructs via seeding with stem cells. The biocompatibility of such templates was tested under in vitro conditions using a dynamic culture of human mesenchymal stem cells. The effects of the mechanical loading of cell‐seeded templates under in vitro conditions were assessed via subjecting the tissue constructs to 28 days of daily mechanical stimulation. The frequency of loading was found to have a significant effect on the rate of mineralization, as the alkaline phosphatase activity and calcium deposition were determined to be particularly high at the typical walking frequency of 2 Hz, suggesting that mechanical stimulation plays a significant role in facilitating the healing process of bone defects. Utilization of such patient‐specific and biocompatible graft substitutes, coupled with patient’s bone marrow cells seeded and exposed to mechanical stimulation of 2 Hz have the potential of reducing significant volumes of cadaveric tissue required, improving long‐term graft stability and incorporation, and alleviating financial burdens associated with delayed or failed fusions of long bone defects.     

Problems of differential diagnosis in a case of bone lesions caused by myelosclerosis associated with hyperparathyroidism

The authors present a report on the case of a female patient with myelofibrosis where X-ray examinations of the bone skeleton predominantly showed such osteolytic changes which are no typical of myelosclerosis. Morphological criteria rather would have corresponded to osteitis fibrosa cystica generalisata. Laboratory examinations partially indicated primary hyperparathyroidism, this assumption could not be confirmed by other examinations. Also histological findings of repeated bone biopsies did not lead to a uniform diagnosis. Autopsy confirmed the presence of both diseases. The authors consider the synergistic effect of both diseases to be the cause for the development of those bone changes mentioned above.     

Skeletal Scintigraphy

Skeletal scintigraphy, using phosphates or diphosphonates labeled with technetium 99m, is a sensitive method of detecting bone abnormalities. The most important and most frequent role of bone scanning is evaluating the skeletal areas in patients who have a primary cancer, especially a malignant condition that has a tendency to spread to bone areas. The bone scan is superior to bone radiographs in diagnosing these abnormalities; 15 percent to 25 percent of patients with breast, prostate or lung cancer, who have normal roentgenograms, also have abnormal scintigrams due to metastases. The majority of bone metastases appear as hot spots on the scan and are easily recognized. The incidence of abnormal bone scans in patients with early stages (I and II) of breast cancer varies from 6 percent to 26 percent, but almost invariably those patients with scan abnormalities have a poor prognosis and should be considered for additional therapies. Progression or regression of bony lesions can be defined through scanning, and abnormal areas can be identified for biopsy. The incidence of metastases in solitary scan lesions in patients with known primary tumors varies from 20 percent to 64 percent. Bone scintigraphy shows positive uptake in 95 percent of cases with acute osteomyelitis. Stress fractures and trauma suspected in battered babies can be diagnosed by scanning before there is radiological evidence. The procedure is free from acute or long-term side effects and, except in cases of very young patients, sedation is seldom necessary.Although the test is sensitive, it is not specific and therefore it is difficult to overemphasize the importance of clinical, radiographic, biochemical and scanning correlation in each patient.     

Novel technology to provide an enriched therapeutic cell concentrate from bone marrow aspirate

Current strategies to repair fractures rely on orthopaedic surgeons harvesting bone from one area of the body, typically pelvis and transferring it to the fracture site. The amount of tissue available is therefore limited, requiring a second surgical procedure and often causing the patient long term pain. An alternative approach is utilise therapeutic cells contained within bone marrow aspirate during the primary procedure. The number of therapeutic cells within a fresh aspirate is insufficient to provide clinically acceptable bone healing in a timescale that is satisfactory to the surgeon and the patient. Therefore methods to efficiently concentrate bone marrow in the clinical setting are required. Centrifugation is the current method of choice but has limitations in that it requires large capital equipment, servicing and there are potential issues of tissue contamination. We have developed a novel, acoustically‐assisted filtration device that addresses these limitations, delivering a concentrated bone marrow in a point of care, single use, fully disposable, compact device. An additional advantage is that the level of concentration required can be specified by the end user. The resulting bone marrow concentrate has been characterised in terms of cell number, viability and osteogenic potential using flow cytometry and alkaline phosphatase assay. When compared to recent clinical studies using bone marrow to repair non‐union fractures, the findings from our work suggest that the bone marrow concentrate is likely to be highly therapeutic and clinically efficacious as a bone fracture repair strategy. A product concept for use in the clinical setting is presented. © 2010 American Institute of Chemical Engineers Biotechnol. Prog., 2010     

Early experience with the Autophor prosthesis using a posterior approach

Twenty-eight Autophor hip prostheses have been implanted in 25 patients, using primarily a posterior approach. Complications have included two dislocations and two femoral shaft fractures. One dislocation required reoperation. The shaft fractures healed in three months with bone grafting and cerclage wiring. There were no infections and no cases of loosening or component failure. Radiological follow-up including bone scan suggests implant boney stabilization at six months. Our early experience suggests that this implant is quite successful, especially in the young patient and the patient with significant loss of bone stock from protrusio or revision surgery.     

Monoclonal antibodies to carbohydrate antigens in autologous bone marrow transplantation

Normal and malignant myeloid cells express a highly immunogenic oligosaccharide, lacto-n-fucopentaose-III (LNF-III), that has been identified by numerous monoclonal antibodies (MoAb). We have been interested in the use of a particular monoclonal antibody to LNF-III, PM-81, in the treatment of patients with acute myelogenous leukemia using the antibody to treat bone marrow in vitro. Following in vitro treatment of bone marrow with PM-81 and another MoAb, AML-2-23, the remaining cells are used as an autograft in a patient treated with high-dose chemotherapy and radiotherapy. In order to enhance the ability of the MoAb to lyse leukemic cells in the remission bone marrow, we have explored the effect of neuraminidase treatment on leukemia cells. In this paper we describe that myeloid leukemia cells expressing low levels of LNF-III by immunofluorescence can be shown to have high levels of LNF-III after neuraminidase treatment. In addition, we show that normal bone marrow progenitor cells do not have cryptic LNF-III antigen, thus allowing the application of this finding to the clinical setting. Moreover, we have shown that leukemia colony-forming cells from one patient with acute myelogenous leukemia express cryptic LNF-III and that after exposure to neuraminidase there was an increased ability of PM-81 in the presence of complement to eliminate these colony forming cells. These data indicate that the LNF-III moiety is almost universally expressed on myeloid leukemia cells and their progenitors but not expressed on normal progenitors. Thus, it may be possible to enhance leukemia cell kill in vitro by neuraminidase treatment of bone marrow.     

Detection of T-precursor cells in human bone marrow and foetal liver.

Human lymphoid cells that have been incubated with conditioned medium from confluent monolayers of human thymic epithelium (HTCM) show an increase in cells forming rosettes with sheep erythrocytes at 4 degrees C (E-rosettes). Those cells demonstrating this in vitro conversion have been interpreted to be T-cell precursors. Separation of human bone marrow cells on discontinuous bovine serum albumin (BSA) gradients, and on a single-step 23% BSA gradient showed enrichment of these T-precursor cells, not only in bone marrow, but also in human foetal liver cells. Bone marrow precursor cells from a patient with Wiskott-Aldrich syndrome (T-cell deficiency) showed a normal in vitro response to HTCM, but no response was seen in cells from a patient with severe combined immunodeficiency disease.     

Lengthening of the reconstructed mandible using extraoral distraction devices: report of five cases

Fibular and scapular osteocutaneous free-tissue transfer represents the workhorse procedure in the reconstruction of large oromandibular defects. However, transplanted bone segments for mandibular reconstruction may be too short for a correct interarch alignment, which is a prerequisite for further functional rehabilitation. Extraoral distraction osteogenesis was performed in the neomandible of five patients after tumor resection following neoadjuvant radiotherapy-chemotherapy. The neomandible was distracted bilaterally in two patients and unilaterally in three patients. Gradual distraction was applied at a rate of 0.5 mm twice a day after osteotomy in the region of vascularized fibular and scapular reconstruction. An average sagittal bone gain of 11 mm was achieved following active distraction. In three patients, the distraction procedure rendered good results with full compensation of the deficit; in one patient, the sagittal bone gain did not compensate for a lateral deviation of the mandible; and in another patient, the fixation pins loosened and had to be reaffixed. Osteodistraction is a treatment option in patients in whom vascularized bone grafts have been used for mandibular reconstruction, but due to contractures or lack of hard and soft tissues, no satisfactory interarch alignment could be achieved. Distraction procedures in irradiated and reconstructed neomandibles bear a higher risk of failure and complications than those in nonirradiated tissues. A correct and stable intermaxillary relation always has to be attempted in the first surgical approach, as osteodistraction cannot be suggested as a routine procedure in this special group of patients.     

Deep-freeze preservation of cranial bones for future cranioplasty: nine years of experience in Soroka University Medical Center

Background Decompressive craniectomy is routinely performed in many neurosurgical centers to treat intracranial hypertension refractory to medical therapy as a result of head trauma, CVA or various brain tumors. When the patient survives his illness, cranioplasty with autologous bone graft or other reconstructive materials is considered to repair the skull defect. Objective This prospective study reviews the cases of decompressive craniectomies followed by later cranioplasty undertaken at our institute through the years 1996 and 2005 and describes the method used for preservation of removed bone flaps for future cranioplasty. Subjects and methods Sixty-eight patients underwent decompressive craniectomies since 1996. A protocol was designed to prepare the removed bone flaps for deep freeze preservation. After removal, the bone flaps were transferred to the skin bank at our institution within 6 h, gently rinsed using 1–3 liters of sterile saline (0.9% NaCl) supplemented with antibiotics (neomycin, 2 mM) with no dimethylsulfoxide (DMSO), then flaps were wrapped in two layers of sterile plastic coverage and preserved at −80°C. Results The patient’s population will be presented. Since 1996 we have performed 12 cranioplasties using deep-freeze preserved autologous bone graft. It took a rather long learning period, beginning with a single patient per year and continued with several others. Up to now, no case of infection, osteomyelitis or bone resorption following cranioplasty have occurred. Conclusion Deep-freeze preservation of autologous bone grafts to reconstruct skull defects after decompressive craniectomy is a useful procedure and has a low revision rate. N. Grossman: deceased 23 December 2006.     

La maladie d’Erdheim-Chester : à propos d’un cas

IntroductionErdheim-Chester disease (ECD) is a rare form of non-Langerhans histiocytosis of which prevalence is difficult to estimate. To date, 178 cases have been published. Its pathophysiology is still unknown. It is characterized by an infiltration of foamy histiocytes within several organs, mainly bone, retroperitoneum, lung, heart, brain and retro-orbital tissue.ObservationWe present the case of ECD in a 62-year-old woman with neurological symptoms, retro-orbital and osseous involvement. Diagnosis was made through an anatomopathological examination of the brain biopsy. A Tc^99m-HDP bone scan revealed a bilateral and symmetric increased uptake of diaphyses and metaphyses of the long bones and a focal increased uptake of the skull. The axial skeleton is spared. The evolution of this patient was marked by recurrences of cerebral localizations and by worsening of neurological deficits. The patient was treated by corticosteroids.Discussion and conclusionErdheim-Chester is a rare non-Langerhans histiocytosis showing characteristic radiological and histological features. Extraskeletal manifestations can occur in almost all organs, leading to a poor prognosis. The diagnosis requires biopsy with histologic confirmation of an extraosseous site. Because clinical bone symptoms can be mild or absent, bone scan may be valuable, as it discloses all sites of bone affected in one diagnostic procedure.     

La scintigraphie osseuse en trois phases pancorporelles

Performing three-phase whole-body bone scan is easy on every patient, does not increase the radiation burden to the patient and enhances the diagnostic value of the procedure. It should be performed almost routinely on every patient scheduled for a bone scan.     

Spurious Case of XX Maleness in A Patient With A History of Wiskott-Aldrich Syndrome

ObjectiveTo alert endocrinologists about the potential for karyotype confusion in patients who have undergone bone marrow transplantation.MethodsClinical, laboratory, and imaging data are reported on a young adult male patient who initially presented because of concerns about short stature.ResultsAn 18-year-old fully virilized male patient with a history of Wiskott-Aldrich syndrome had undergone successful bone marrow transplantation in infancy. The donor was his older sister. Many years later, he underwent evaluation because of short stature and was found to have a 46, XX karyotype. This unexpected finding led to several costly laboratory and imaging studies, as well as a new diagnosis of a disorder of sex development. The patient was referred to our medical center for further evaluation of XX sex reversal. A skin biopsy was eventually performed, which revealed a 46, XY karyotype. This unusual case highlights the fact that a peripheral blood specimen from bone marrow transplant recipients reflects the genetic makeup of the bone marrow donor.ConclusionAlthough the cytogenetic changes that occur in recipients of bone marrow transplants are well known to hematologists and oncologists, they are not commonly recognized by other health care providers. Increased awareness of this potential situation in long-term survivors of bone marrow transplantation is needed. (Endocr Pract. 2011;17:e1-e3)     

Spontaneous growth of colonies with mature T lineage phenotype from T-cell-depleted bone marrow precursors in a patient with a lymphoproliferative disorder of the large granular lymphocytes

Bone marrow cells from a patient with pancytopenia and a lymphoproliferative disorder of large granular lymphocytes (LGL) were cultured and tested for their hemopoietic colony-forming potential. Neither erythroid nor granulocyte-macrophage colony formation could be obtained from unfractionated, or LGL-depleted bone marrow cell preparations. However, a spontaneous growth of lymphoid colonies was observed after culturing LGL-depleted (T3-) bone marrow cell suspensions for 25 days. Pooled colonies expanded with recombinant interleukin-2 yielded a population composed predominantly of mature T cells (T3+, Leu 6-). These findings suggest that some (T3-) T cell precursors may mature in the bone marrow and that, in our patient, LGL may have exerted a suppressor effect on this maturational process.     

HLA compatibility for patients with thalassemia: implications for bone marrow transplantation

In order to evaluate the possibility of a patient with thalassemia finding an HLA-identical sibling donor, we performed an analysis of HLA antigens in families of thalassemic patients. The pattern distribution was not significantly different from the expected ratio 25:50:25. When the siblings were subdivided according to the age of the patients (under or over 5 years), the above pattern remained unmodified for both the age groups. The average size of the 129 thalassemic families was 2.4. Thus, taking into account that thalassemic patients have an average of 1.4 siblings and that the HLA genotype distribution is expected as such, HLA-matched siblings are available for 33% of the patients. Because an additional 8.5% of the patients were found HLA-phenotypically identical to one parent, the chance for a patient with thalassemia to find a suitable donor for bone marrow transplantation would be increased to 41.5%. Our preliminary data cannot be extrapolated to the overall Italian thalassemic population; however, it can be inferred that for a patient with thalassemia, the chance of finding a suitable donor for bone marrow transplantation is not reduced.     

Aggressive multifocal form of epithelioid hemangioendothelioma--case report

Epithelioid hemangioendothelioma (EHE) is a rare tumor of the vascular origin. It was first described in its pulmonary form by Dail and Leibow in 1975 and named "intravascular bronchioalveolar tumor" (IVBAT). Since then, reports of occurrences of the tumor have been made for number of locations, but most often tumor can be found in soft tissues, liver, lungs, bone and skin. It is considered to be a low or borderline malignant tumor with, usually, slow progression, but aggressive forms have been described. We here report a case of a 46-year old female patient with multifocal malignant tumor spreading to lungs, liver, spleen and with synchronous involvement of lumbal vertebrae, illiac bones and central nervous system dissemination. To the best of the authors knowledge, no case of malignant EHE with multiorgan involvement of this proportions and synchronous central nervous system and bone involvement in one patient has been reported to this date in English-speaking literature.     

Case report: restoration of edentulous mandible with 4 BOI implants in an immediate load procedure

Dental implants for insertion from the lateral aspects of the jaw bone have been described repeatedly, since 1972. Long term results have been reported. Due to their design, BOI-Implants (basal osseointegration) can be installed even in those cases, where the vertical bone supply is reduced. This applies to the distal areas of the maxilla and the mandible. Furthermore, BOI-implants allow immediate loading as long as a balanced masticatory function can be achieved and maintained. This paper reports on the steps taken to install a full lower bridge in 4 BOI-implants and restoration in a patient with a circular bridge. The bridge was made from CoCr-Alloy and covered with acrylic resin. This treatment technique reduces costs and treatment time by about 50% compared to conventional techniques.     

A combined RSA and FE study of the implanted proximal tibia: correlation of the post-operative mechanical environment with implant migration

There is strong evidence to suggest that inducible displacements, migration and implant loosening are closely related to the initial mechanical environment of the implanted tibia. If this is true, then it should be possible to predict the likelihood of implant migration using patient-specific finite element models. Finite element models of the proximal implanted tibiae were analysed based on pre-operative quantitative computed tomography data of four patients entered into a radiographic migration study. These four patients were also part of an radiostereometric analysis (RSA) study. A variety of load cases were analysed and the risk of bone failure determined for a 2 mm layer of bone immediately beneath the tibial tray. The results were compared with the RSA data measured 1 year post-operatively for each patient. For each patient, an appropriate load case was selected based on patient weight and on the varus-valgus migrations observed in the migration study. The two patients with press-fit implants were predicted to have the highest risk of failure and were found to migrate the most. The two patients with bonded implants (one HA coated and one cemented) were found to have a low risk of failure and these implants migrated the least. This study suggests that the degree of implant migration is dependent on the initial mechanical environment and can be determined using patient-specific finite element analysis.     

Nuclear medicine studies of aging—III. Radial bone mineral content by single and dual photon absorptiometry

Measurement of bone mineral content of the radius has been possible by single photon absorptiometry. Recently, dual photon devices have become widely used for measuring the quantity of lumbar vertebral bone mineral. Therefore, we studied the utility of a dual beam machine for quantifying the bone mineral content of the radius, and compared results with those obtained by single photon absorptiometry in the same patient on the same day. There was an excellent correlation between single and dual beam measurements of the radius. The present study indicates that a dual photon machine can be used for assessing not only vertebral, but radial bone mineral content as well. This may facilitate studies of the two sites by use of one machine.     

Changes in Skeletal Mineral in Patients on Prolonged Maintenance Dialysis

The measurement of bone loss in patients undergoing maintenance dialysis over a period of two and a half years is reported. The tendency to lose bone is a likely event in renal failure, but depends more on the individual patient than on the type of dialysis used, provided that steps are taken to prevent avoidable calcium loss during dialysis. Vitamin D therapy was an important factor in preventing bone loss in some cases. The tendency to lose bone more readily when both kidneys were absent may have reflected a deficiency of 1-25 dihydrocholecalciferol. On the other hand, bone loss was also observed in transplanted patients. The need to measure bone loss at regular intervals once renal failure has been diagnosed is stressed.     

Intraosseous vascular malformations of the orbit

Intraosseous vascular malformations are rare benign tumors involving the bones of the orbit. The diagnosis should be considered when a patient presents with an enlarging mass fixed to bone in the upper face, and the characteristic x-ray appearance should be looked for on plain films. Treatment is local excision of the bone containing the tumor and immediate reconstruction with autogenous bone.