The significance of histology in relation to non-invasive techniques in the evaluation of bone tissue.
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Bone Remodeling↗
Biomedical subjects
G Delling
Publications and source records attributed to G Delling.
[Pathologic humeral fracture in secondary osteosarcoma of the humerus: a rare complication of osteodystrophia deformans Paget].
Pathological fracture in histologically proven post-Paget osteosarcoma of the humerus is a rare complication. Due to individual requests as well as age and comorbidity, a course of primary palliative treatment was chosen in the present case. Survival time after diagnosis was 9 months and the patient died of a tumor-independent disease. Even in combined treatment, consisting of surgery and (neo-)adjuvant radio-/chemotherapy, prognosis of osteosarcomas secondary to Paget's disease remains very disappointing. Therefore, in treatment of this highly lethal tumor the patient's individual requests and personal situation often require more consideration than in many other malignancies.
Aged↗
P-glycoprotein expression in high grade central osteosarcoma and normal bone cells. An immunohistochemical study.
One important mechanism by which multidrug resistance is mediated is the mdr1 gene product, P-glycoprotein (Pgp). Even though chemotherapy, in the treatment of high grade central osteosarcoma (hgc-OS), has led to dramatic improvements in survival rate, a certain percentage of patients still show only a poor response to chemotherapy. To further characterize a potential connection between Pgp and chemotherapy as well as the role of Pgp in tumorigenesis of osteosarcoma, we analyzed Pgp-expression in hcg-OS. Immunohistochemistry was performed on 68 hgc-OS samples from 58 patients using the monoclonal antibody JSB-1; in addition, Pgp-expression in normal bone cells was studied in 5 human epiphyseal growth plates. 70.5% of all cases stained positive for P-glycoprotein, while 29.5% of the cases were negative. Cases investigated after chemotherapy showed a higher incidence (82.9%) of positive P-glycoprotein immunostaining than cases prior to chemotherapy (64.4%). The Pgp-expression of 34 biopsies was compared with chemotherapy, as determined at the surgical specimen. In these cases, however, no correlation could be established between P-glycoprotein expression of the biopsy and the later response to chemotherapy. 48.4% of the cases with biopsies, initially positive for Pgp, showed a good response in the surgical specimen, while only 27.2% of Pgp-positive biopsies were later classified as non-responders. In the normally growing skeleton, positive immunostaining was detected in the area of mineralization of epiphyseal growth plates. Osteoclasts, hypertrophic chondrocytes, and cuboidal osteoblasts showed Pgp-expression, while there was a lack of Pgp in the majority of osteocytes and chondrocytes in the resting and proliferating zone. These data therefore suggest that P-glycoprotein expression in hgc-OS resembles, at least in part, the phenotype of active bone cells. These results may explain why P-glycoprotein, by using immunohistochemistry, in biopsies of osteosarcomas is insufficient to predict the response to chemotherapy.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Heterogeneity of the skeleton: comparison of the trabecular microarchitecture of the spine, the iliac crest, the femur, and the calcaneus.
The objective of this study was to elucidate the structure of cancellous bone and its age-related changes at different skeletal sites. Therefore, the lumbar spine, iliac crest, femur, and calcaneus of 12 age- and sex-matched skeletal healthy autopsy cases (6 females, 6 males, aged 28-84 years, mean 54 years) were removed. The following analysis includes an evaluation of the trabecular bone volume (BV/TV, %) and the trabecular interconnection (TBPf, mm-1) as well as a qualitative investigation of the structure of trabecular bone. BV/TV shows the following mean values: lumbar spine, 8.3% (+/- 0.8%); iliac crest, 11.5% (+/- 1.6%); intertrochanteric, 10.2% (+/- 1.2%); femoral neck, 15.8% (+/- 1.6%); and calcaneus, 15.4% (+/- 2.0%). There are significant differences between the BV/TV of the femoral neck and that of the lumbar spine as well as between that of the calcaneus and the lumbar spine (p < 0.01). However, a positive correlation can be seen between the bone mass of the spine and that of all other investigated sites (r = 0.67 to r = 0.80; pr < 0.1). The trabecular interconnection of the lumbar spine (2.7 mm-1, SEM +/- 0.2 mm-1) and the femoral neck (0.3 mm-1, SEM +/- 0.3 mm-1) differs significantly. Only these two sites show a significant positive correlation of TBPf (r = 0.60; pr < 0.1). Age-dependent alteration of the spine and the femoral neck in bone mass and bone structure is nearly the same. The trabecular microarchitecture of the iliac crest varies systematically. A region 4-10 cm behind and 1-3 cm below the anterior superior iliac spine turns out to be the most suitable biopsy site because of its closest relation to the lumbar bone mass. However, drawing information about the trabecular interconnection within the lumbar spine by measurement of the iliac crest at any site seems to be impossible. The horizontal specimens reveal a vertical running tubular spongiosa pattern that is arranged in concentric rings starting from the dorsal shell like a honeycomb. The comparison of TBPf in horizontal and vertical planes and its age-related changes indicates the age-related bone loss to be predominantly a loss of horizontal trabeculae. Thus, the presented data provide further information about the skeletal distribution and heterogeneity of the trabecular microarchitecture.
Adult↗
Architecture and distribution of cancellous bone yield vertebral fracture clues. A histomorphometric analysis of the complete spinal column from 40 autopsy specimens.
The objective of this study was to analyze the structure of cancellous bone and its significance for vertebral fractures. Therefore, the complete spinal column from 40 autopsy cases (18 without diseases affecting the skeleton and 12 osteoporotic) was removed and sectioned in the sagittal plane to a thickness of 1 mm. A surface-stained block grinding technique allowed combined two- and three-dimensional histomorphometric analysis, which included an evaluation of the trabecular bone volume (BV/TV, in %) and the trabecular interconnection (TBPf, in mm). In addition, qualitative investigation of the structure of trabecular bone was done. The distribution of trabecular bone volume within the spinal column of a normal skeleton shows a curve, with the highest values in the cervical spine and a decline in the thoracic and lumbar spine. Osteoporosis presents itself with a pathologically diminished trabecular bone volume, whereas the distribution within the spine is comparable to that of the controls. Osteoporotic patients show an apparently reduced trabecular interconnection. It is important that the measured values for TBPf are not only in general higher, but also more widely dispersed. The age-related decrease of trabecular bone mass is due to the transformation from plates to rods. This is quantitatively indicated by the close correlation of BV/TV and TBPf (P < 0.001, r = 0.85). The bone loss in osteoporosis is a loss of structure and a loss of whole trabeculae, which is caused by perforations. It involves a gradual change from normal bone. However, the polyostic heterogeneity in osteoporosis is immense. These structural differences demonstrate the development of regions of least resistance within the spine, serving as an explanation of osteoporotic fractures. Due to the polyostotic heterogeneity it is impossible to define a threshold mineral content for crash fractures by diagnostic measurements at any reference site.
Adolescent↗
Effect of ovariectomy on bone histology and plasma parameters of bone metabolism in nulliparous and multiparous sows.
To investigate the suitability of the pig as animal model for postmenopausal osteoporosis, effects of ovariectomy (OVX) on bone metabolism and histology were studied in two groups of sows (9 months, nulliparous or 35 months, multiparous). A standard diet of about 1.5% calcium (Ca) was fed till sacrifice at either 12 or 20 months post OVX when mineral content and histology were studied in representative bone specimens of proximal tibia, iliac crest and lumbar vertebrae. At 4, 8, 12, and 18 months post OVX, total and bone-specific alkaline phosphatase (APt, APb) calcidiol, calcitriol and parathyroid hormone (PTH) were measured in plasma. In young sows OVX did not significantly affect plasma variables except for calcitriol, which was higher at 4 months post OVX. No significant differences between OVX or control animals were observed in the variables of bone chemical and histological analyses, neither 12 nor 20 months post OVX. In multiparous sows OVX significantly increased PTH plasma concentrations at 8 months post OVX and plasma calcitriol, APt and APb at 12 months post OVX. All effects were moderate and transient. OVX did not significantly affect the variables of bone chemical and histological analyses neither 12 nor 20 months post OVX. Although undoubtedly the clinical-chemical changes observed were not accompanied by any histomorphometric signs of osteopenia/osteoporosis, it must be left to future experiments as to whether this resulted from the ample calcium supply provided. This possibility is supported by recent observations showing that porcine osteopenia could be induced by OVX in animals maintained on only 0.75% dietary calcium but not on higher (0.9%) Ca regimens.
Aging↗
[Histologic grading of chondrosarcoma. A qualitative and quantitative analysis of 74 cases of the Hamburg bone tumor register].
Chondrosarcomas are frequent malignant bone tumors. Aside from different subtypes, such as dedifferentiated, mesenchymal and clear-cell chondrosarcoma, chondrosarcomas (classical chondrosarcoma) show different grades of differentiation. The borderline between chondroma and classical chondrosarcoma is not clearly defined. The same chondrosarcoma can be graded differently at different institutes. Standardized therapy concepts are currently in preparation. As the Hamburg Bone Tumor Registry is often consulted for chondrogenic tumors, the histological criteria are based on a series of 74 chondrosarcomas recorded there. The emphasis has been laid on a classification which can be used in daily routine and which is reproducible and in agreement with the classifications of other international groups. Grade I chondrosarcomas (50%) can be distinguished only by growth criteria. The nuclei are small and show high chromatin density. Grade II chondrosarcomas (42%) have medium-sized, regular nuclei with loose chromatin structure. The chondrocytes of grade III cases (8%) show polymorphic nuclei. Binucleas forms, the number of mitoses and cellularity all show considerable overlap for all three grades. So far there are no immunohistological and molecular biological methods for reliable differentiation. The therapeutic consequences of the classification into grades are thorough curettage, in the case of grade I tumors, or complete resection, for grade II and III cases. The long-term results, however, need to be confirmed by a larger number of cases. From 1991 to 1995 the method was applied and proved to be easily practicable in daily diagnostic routine. Some 104 cases of classical chondrosarcomas (grade I 53%, grade II 39%, grade III 8%) were analyzed. Two pathologists both assigned the same grade in 90% of cases.
Adult↗
[Morphologic characteristics of chondroblastoma. A retrospective study of 56 cases of the Hamburg bone tumor register].
Representing only about 1% of all primary bone tumors, chondroblastoma constitutes a very rare bone tumor entity. 56 cases of chondroblastoma, that had been collected by the Hamburg Bone Tumor Registry from 1972 to 1995, were examined histologically together with the radiological and clinical findings. In addition immunohistochemistry with antibodies against S 100, PGM1, LCA and the proliferationmarker MIB 1 was performed. The mean age was 20.4 years and male patients being the majority with a gender ratio of 2.7:1. Predominant localisation was the epiphyses of the long bones, although almost 40% of the tumors were located at untypical sites. Usually a well-circumscribed lysis could be seen on plain X-Ray examination, however partial cortical destruction could be observed in one third of the cases. Histologically characteristic was a polygonal cell component with a weblike chonroid matrix, sometimes with a plane-like appearance. 5 cases showed a distinct nuclear polymorphism making a distinction from osteosarcoma difficult. Using immunohistochemistry all tumors except for one showed positive reaction for S 100 protein. Although the histogenesis of chondroblastoma is not completely understood, morphological findings as well as the observed reactivity with the S 100 protein indicate the chondroid origin. No reactivity for PGM 1 (CD 68) or LCA could be detected. All chondroblastoma showed a low rate of proliferation, thereby being distinguishable from high malignant bone tumors. In general chondroblastoma show a benign biological behavior. Different behavior was observed in 2 cases. One relapse located in the pelvis revealed local aggressive growth while in another case in the humerus a malignant transformation had taken place.
Adolescent↗
[P-glycoprotein expression in osteosarcoma].
One of the mechanisms by which multidrug resistance is mediated, is the mdr1 gene product, P-glycooprotein. Immunohistochemistry was performed for 63 osteosarcomas of 54 patients to investigate P-glycoprotein expression using the monoclonal antibody JSB-1. Most of the patients were children or adolescents who had received treatment under the framework of the Cooperative Osteosarcoma Study Group. In addition P-glycoprotein expression was assayed in five growth plates. Of all cases 68.5% stained positive for P-glycoprotein. Cases that had received chemotherapy showed a higher incidence (80.9%) of positive P-glycoprotein immunostaining than cases that had not received chemotherapy (66.6%). No relation could be established between P-glycoprotein expression and the response to chemotherapy, since the majority of P-glycoprotein positive biopsies showed a good response in the surgical specimen after chemotherapy. Furthermore, 42.9% of P-glycoprotein negative biopsies were classified as non-responders in the later surgical specimen. In addition to P-glycoprotein expression in osteosarcomas positive immunostaining was also detected in osteoblasts, osteocytes, osteoclasts as well as in some chondroblasts. The results indicate that P-glycoprotein expression in osteosarcomas also exists prior to chemotherapy and resembles the phenotype of normal bone tissue. However, the determination of P-glycoprotein by using immunohistochemistry in biopsies of osteosarcomas cannot predict the response to chemotherapy.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
[Cell proliferation in bone tumors. Immunohistologic study of Ki-67 protein expression].
Bone tumors represent a group of tumors of various dignity. In spite of this single tumor entities may display strong morphological resemblance to each other which can in turn result in profound difficulties in differential diagnosis. The biological behaviour of a tumor is mainly determined by its rate of proliferation. In this study the rate of proliferation of 64 bone tumors (30 high-grade central osteosarcomas, 6 low-grade osteosarcomas, 8 giant cell tumors, 8 aneurysmatic bone cysts, 5 osteoidosteomas/osteoblastomas, 7 fibrous dysplasias and 5 cases of a myositis ossificans) were analysed. Immunohistochemistry was performed on paraffin-embedded tissue sections using the MIB-1 monoclonal antibody. MIB-1 recognizes the proliferation-associated Ki-67 protein which is expressed during the active phases of the cell cycle but cannot be detected in senescent cells. Among high-grade central osteosarcomas a significantly higher rate of proliferation (average value 30%) was found in comparison with low-grade osteosarcomas and other benign intraosseous bone tumors. This approach proved to be very useful in the distinction between high-grade and low-grade osteosarcomas as well as bone-forming intraosseous tumors. However distinguishing low-grade osteosarcomas from benign bone tumors by determining only the rate of proliferation was not possible, although interestingly, the proliferative rate of myositis ossificans, a purely reactive lesion, was in the range of the values determined for high-grade osteosarcoma.
Biomarkers, Tumor↗
[Solitary bone cysts. Morphologic variation, site, incidence and differential diagnosis].
Analysis of 402 solitary bone cysts demonstrates the wide morphological variation of this cystic lesion with regard to histology and radiology. Aside from metaphyseal location in femur (33%) and humerus (23%), solitary bone cysts are also often located in calcaneus (11%), tibia (11%) and pelvis (10%). Most patients are in the second decade of life. Differentiation between this benign lesion and malignant bone tumors is very important in daily clinical routine. The diagnosis cannot be based solely on radiological findings because of the variation of solitary bone cysts and the special forms, such as calcifying solitary bone cyst. Therefore, exact histological diagnosis is of particular importance.
Adolescent↗
[Spongiosa structure and polyostotic heterogeneity in osteoporosis. Mechanism of bone transformation, morphology, clinical significance].
Osteoporosis is the most frequent generalized bone disease. The clinical expression of postmenopausal osteoporosis is characterized by spontaneous fractures of the vertebral bodies which affect mainly the trabecular bone structure. Thus the morphological bone transformation in osteoporosis is of clinical relevance. The object of this study was to analyze quantitatively and qualitatively the distribution of three-dimensional structure of cancellous bone in the human spine in osteoporosis. Therefore the complete anterior column of the spine and bone biopsies of the iliac crest of 11 autopsy cases with proven osteoporosis and 26 autopsy cases without primary or secondary bone disease were removed. A 1-mm-thick prepared sagittal section through the center of all vertebral bodies was embedded undecalcified in plastic and stained on the surface using a modification of the von Kossa method. This technique allowed combined two- and three-dimensional measurements simultaneously; these included evaluation of trabecular bone volume, trabecular interconnection, trabecular thickness, and trabecular number. The quantitative spine deformity index and qualitative analysis of the trabecular bone structure completed the investigation. The bone loss in osteoporosis is a loss of structure and the loss of whole trabeculae caused by perforations. The age-related decrease of trabecular bone mass is due to the transformation from plates to rods. Patient with osteoporosis show pathologically diminished trabecular bone volume and apparently reduced trabecular interconnection, while trabecular thickness and trabecular number show age-dependent change. The polyostotic heterogeneity in osteoporosis is immense. Neighboring vertebral bodies show differences of up to 100% in bone volume and bone structure. Due to this fact it is impossible to define a threshold for osteoporotic fractures. At the moment the transformation and loss of trabecular bone structure in osteoporosis is assumed to be irreversible; therefore, early prophylaxis is necessary to prevent clinical manifestations of these changes of bone.
Adolescent↗
[Friedrich Daniel von Recklinghausen. Biography and significance of his osteopathologic work after more than 100 years].
Even today the name of F.D. von Recklinghausen is often mentioned in connection with primary and secondary hyperparathyroidism. He was one of the first physicians and scientists to render outstanding services to the classification of structural changes of bones, and in many aspects his work remains valid today. He succeeded through precise and comparative studies in making the disease and symptoms of primary hyperparathyroidism known and thus distinguishing it from other known structural bone diseases. He also described the phenomenon of "bone remodeling" which has become relevant today again. Although his written macroscopic and microscopic observations include meticulously precise differentiations which make it difficult to study them today, they are still of interest in order to follow his basic ideas. This article does not constitute a comprehensive biography, but it contains a description of F.D. von Recklinghausen's important work on bone pathology against the background of the main stages of his life.
Bone and Bones↗
[Archiving of pathologic-anatomic findings in bone diseases and bone neoplasms in individual databanks. Experiences of a new enterprise with applicable outcome].
In this paper my experience with a databank for cases with bone diseases is reported. All cases which had been diagnosed in the newly formed Department of Bone Pathology of the University of Hamburg since 1970 were registered in uniform fashion. Adapting the system to state-of-the-art network structures required a lot of personal and financial investment. This could not be accomplished by university resources alone, but only in cooperation with other research funds. Now 76,000 cases can be routinely accessed and scientifically analysed.
Bone Diseases↗
[Periosteal osteosarcoma. Histologic characteristics, preparation technique, growth pattern and differential diagnosis].
Periosteal osteosarcoma is a distinct bone tumor entity with characteristic morphological features within the group of juxtacortical osteosarcoma. Periosteal osteosarcoma is predominantly located in the long tubular bones, especially in the tibia and femur and is situated on the outer circumference of the tumor-bearing bone (saucerization phenomenon). In contrast to parosteal osteosarcoma, periosteal osteosarcoma is less differentiated and is believed to have a worse prognosis. In this work the histological features are described with predominantly chondroblastic differentiation of 14 cases with periosteal osteosarcoma. A horizontal preparation technique of periosteal osteosarcoma specimens allows comparison with computed tomography and is the optimal method to detect an invasion of the medullary cavity. Further studies are necessary to clarify if neoadjuvant chemotherapy could improve the prognosis of certain patients.
Adolescent↗
[Cell biology of osteoclasts and molecular mechanisms of bone resorption].
The maintenance of a normal skeletal shape and bone mass closely depends on a normal osteoclastic activity, as do bone growth and repair. Thus, the improvement of our means of therapeutic intervention will depend on our better understanding of the molecular basis of bone resorption and of the cellbiology of the osteoclast. This review-article presents our current opinion of the molecular mechanisms of bone resorption by the osteoclast. After describing the morphological features of the osteoclast, aspects as cell mobility, attachment, enzymesynthesis, transmembrane transport, osteoclast differentiation and function, as well as the protooncogenes c-src and c-cbl and their role for bone resorption are presented in detail.
Animals↗
[Comparative DNA cytometric and cytogenetic ploidy determination of chondrosarcoma and osteosarcoma].
10 chondrosarcomas and 10 osteosarcomas were examined using cytogenetics and DNA-image-cytometry. Cytogenetically 6 of 10 chondrosarcomas and 4 of 10 osteosarcomas showed hyperdiploid tumorcells. By DNA-cytometry in 8 of 10 chondrosarcomas and 9 of 10 osteosarcomas hyperdiploid tumorcells resp. hyperdiploid stemlines were detected. This discrepancy reflects an in-vitro-selection depending on the different entities. In 7 aneuploid clones of chondrosarcomas the chromosomal ploidy was calculated using the relative length of the chromosomes and compared with the DNA-ploidy of the native tumor. There was a close relation between both parameters of nuclear DNA-content. The interpretation of cytogenetic results is improved using a combination of karyotypic and DNA-cytometric examination. This is particularly important for the search for relations between numeric chromosomal aberrations and morphological parameters (grading).
Aneuploidy↗
Morphometric analysis of noninvasively assessed bone biopsies: comparison of high-resolution computed tomography and histologic sections.
This article describes a new method to analyze the structural behavior of trabecular bone structure by means of noninvasive measurements of the three-dimensional cancellous bone architecture. For the noninvasive data acquisition, a high-resolution quantitative computed tomography system for peripheral measuring sites (pQCT) was used. With this system and the help of a multiple thin-slice measuring technique, it became possible to examine three-dimensional bone structure with a resolution of 0.25 mm. Using a special three-dimensional segmentation algorithm, mineralized bone was separated from bone marrow and muscle tissue within the three-dimensional stack of CT slices. These segmented data sets can then be processed nondestructively and, even more important, repetitively in either two or three dimensions. In order to validate this noninvasive procedure, a two-dimensional comparative morphometric study was performed including CT slices and corresponding histologic sections prepared after CT measurement. Three representative sections from the three-dimensional stack of CT slices were selected and the morphometric indices of the segmented CT slices were compared with the indices stemming from the corresponding histologic sections prepared after CT measurement. Although the presented approach can only give an example of the method, the results from the morphometric analysis support the assumption that cancellous bone structures based on noninvasive high-resolution CT measurements are representative for trabecular microstructures assessed from histologic bone sections. The study demonstrates the potential of high-resolution CT imaging for in vivo applications of quantitative bone morphometry. This is especially true for repetitive follow-up measurements, which cannot be performed using histologic sections. Additionally, the method offers an easy access to the three-dimensional structure of trabecular bone, which is mandatory for the analyses of the anisotropic mechanical behavior of cancellous bone.
Algorithms↗