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Zoledronic acid to prevent bone loss in the first 6 months after renal transplantation. Bisphosphonates can prevent bone mineral density loss after renal transplantation, but their effect on trabecular mineralization and bone morphology, two key factors of bone stability, remains unknown. In a 6-month, randomized, placebo-controlled study, 20 kidney transplant recipients received either 4 mg zoledronic acid or placebo twice within 3 months after engraftment. At transplantation and after 6 months, mean trabecular calcium concentration and trabecular morphometry were measured in bone biopsies. Bone mineral density (BMD) of the femoral neck and the lumbar spine were evaluated by dual-energy x-ray absorptiometry, and serum biochemical markers of bone metabolism were determined monthly. Trabecular calcium content increased significantly in the zoledronic acid group, but remained unchanged in the placebo group. BMD at femoral neck showed no change in the zoledronic acid group, but decreased in the placebo group. BMD of the lumbar spine was increased in the zoledronic acid group without change in the placebo group. High-turnover bone disease resolved similarly in both groups, as evidenced by a significant decrease of eroded bone surface, osteoclast and osteoblast surface. Serologic markers of bone formation and resorption were significantly lower in zoledronic acid-treated patients throughout the study. Kidney transplant function was stable after zoledronic acid therapy. Our results show that administration of zoledronic acid improves the calcium content of cancellous bone after kidney transplantation. The beneficial effect of bisphosphonate therapy is further evidenced by an increase of lumbar spine BMD, and stabilization of femur BMD.

We report on 13 patients with dedifferentiated chondrosarcomas. The mean age of the patients at diagnosis was 59.8 years. Nine patients were classified as stage IIB and four as stage III. In 11/13 cases surgery was performed. Mostly, limb salvage with tumour resection and implantation of a megaprosthesis was done; three patients needed amputation or disarticulation. In one out of three patients with a pelvic tumour resection was followed by implantation of a pelvic replacement; the other two patients received tumour resection with autologous stabilisation of the pelvis. Surgical margins were wide in six patients, marginal in two and intralesional in three. Adjuvant chemotherapy was given to five patients. Recurrence was detected in 5/11 of the patients operated on: in two with wide, in one with marginal, and in two with intralesional resection. No recurrence was seen in 5/11 patients: in four after wide and in one after marginal resection. In one patient the stage was unknown. At follow-up 11 patients were dead of disease (DOD), one dead of unknown reason (DOU) and one alive with disease (AWD). The mean survival time was 9.7 months. Metastasis to different anatomical sites was evident after a period of 10 months. Our results resemble those reported in the literature. DDCS is rare and is the primary malignant bone tumour with the worst prognosis. Surgery is the most important procedure, although it is unclear whether a radical resection improves the long-term results. Information regarding neoadjuvant and/or adjuvant therapy with chemotherapy is very limited.

Giant cell tumor of bone (GCT) is a locally osteolytic tumor with variable aggressiveness. In rare cases, pulmonary metastasis can be observed. The lesion most frequently occurs in the epiphysis of long tubular bones of the knee region, predominantly affecting young adults after closure of the growth plate. The characteristic histological appearance of GCT displays a high number of osteoclast-like multinucleated giant cells, which resulted in the classification \"osteoclastoma\" or \"giant cell tumor\". Apart from the multinucleated giant cells, there are two mononuclear cell types in GCT. The first one has a round morphology and resembles monocytes. The second cell type is the spindle-shaped, fibroblast-like stromal cell. Cell culture experiments with GCT cells revealed the stromal cell to be the proliferating component of the GCT. The other two cell types, the monocyte and the multinucleated giant cell, were lost after a few cell culture passages. Furthermore, latest results from GCT reveal that the stromal cells secrete a variety of cytokines and differentiation factors, including MCP1, ODF, and M-CSF. These molecules are monocyte chemoattractants and are essential for osteoclast differentiation, suggesting that the stromal cell stimulates blood monocyte immigration into tumor tissue and enhances their fusion into osteoclast-like, multinucleated giant cells. The multinucleated giant cell itself resembles a normal osteoclast that is able to resorb bone leading to extended osteolysis. This new model of GCT genesis supports the hypothesis that the stromal cell is the neoplastic component whilst the monocytes and the multinucleated giant cells are just reactive components of this tumor. Taking this into consideration, the nomenclature of the \"giant cell tumor\" needs to be reconsidered.

Anteroposterior procedures for lumbar interbody fusion usually combine posterior instrumentation with anterior techniques that achieve primary stability for compressive loading: tricortical strut-graft, anterior plating systems, or cages. In comparison to transpedicular lumbar interbody fusion (TLIF), these methods bear the burden of the additional anterior approach. TLIF with autograft, in contrast, does not prove to be clinically sufficient because of its lack of primary compressive stability. In a sheep model, we therefore developed a TLIF method providing primary stability for axial loading. In 24 sheep, L4-L6 were instrumented posteriorly. An endoscopically assisted L4/L5 TLIF procedure was performed via a bilateral approach. In 12 sheep, the defect was filled with an injectable calcium phosphate cement. After setting, this cement gains a stability against axial loading comparable to healthy vertebrae. Another 12 sheep were treated with autograft. The animals were killed at 8 weeks and evaluated by radiologic (plain X-ray, computed tomography), histologic and histomorphometric analysis, and fluorochrome labeling. Only ten autograft sheep were available for evaluation. Radiologically and histologically, TLIF with calcium phosphate led to a 2/12 fusion rate compared to autograft (1/10 fused) (P=0.70). Semiquantitative radiologic and histologic scoring did not reveal significant differences (P=0.88). In 4/12 calcium phosphate sheep, excessive resorption was responsible for local aseptic inflammation. The findings of this study show that calcium phosphate cement is not superior to autograft, despite enabling primary stability against compressive loading. Biointegration of the osteoconductive cement does not occur fast enough, and shear forces cause early cement fracture, subsequent fragmentation, and gross resorption with the possibility of severe inflammation.

In the past, six histological grading systems for classical chondrosarcoma have been published. Due to the inhomogeneity and complexity of these classifications, the comparison of clinical data, survival rates and local failures has to be considered critically. In 1996, the author published a grading system that was simple to use and easily reproduced. This system was based on a few nuclear features. The main intention of the current study was to verify whether the histological grade, which was defined by the author's classification, correlates with the recurrence rate. In a retrospective study, clinical data, X-rays and histological material from 35 patients with classical chondrosarcoma and 16 patients with enchondroma were analysed. Statistical analysis was done using the chi-squared test and the Fisher exact test. Local recurrence occurred in 25.7% of all patients. The difference in recurrence rate among grades 1-3 was statistically significant ( P=0.002). The frequency of grades 1-3 varied up to 54%, when published grading systems were compared. No significant difference between the histological grade and features such as double nuclei and mitosis were observed. The frequency of cellularity, double nuclei and mitoses was similar between enchondromas and low-grade chondrosarcomas. Of chondrosarcoma patients, 90.6% of total patients and 87.5% of those with grade-1 lesions reported pain, whereas only 43.8% of the enchondroma patients did. Even in patients with grade-1 chondrosarcomas, radiological findings were much more aggressive in comparison with enchondromas. The histological grade, defined on the basis of the author's simple and reproducible grading system, indicates the risk of local recurrence, especially in cases that are inadequately treated. Grade-3 chondrosarcomas and lesions located in regions where the removal of the tumour would be difficult have to be given special attention.

Bone biopsy is a diagnostic procedure restricted to untypical, unclear and complicated cases in evidence-based guidelines on diagnosis and treatment of osteoporosis. Its relevance has been a topic of recent controversial discussion. This study was performed to evaluate its role and relevance in routine use. A total of 99 horizontal transiliac bone biopsies performed over a time period of 14 years because of an osteological indication in one single centre were analysed, which reflects that bone biopsy followed about 0.003% of patients' consultations. Bone biopsies were indicated for osteoporotic males (n = 63) and premenopausal osteoporotic females (n = 18) without endocrine abnormality and normal immunofixation (serum and urine), suspected systemic/malignant disease such as mastocytosis, osteogenesis imperfecta, non-secreting plasmocytoma, metastatic infiltration (n = 16) and decreasing bone mineral density under anti-osteoporotic treatment (n = 2). The most frequent diagnoses besides osteoporosis were normal histology, borderline finding towards mild osteoporosis, and osteoporomalacia with relevant osteoidosis. In some cases, pathological findings in bone marrow were detected. In most cases (82/99), bone biopsy led to consequences in medical treatment. Following histopathological diagnosis, 16 patients did not receive any anti-osteoporotic treatment. In six patients, further diagnostic procedures were initiated because of bone histology. Bone biopsy was well tolerated and complications were rare and mild. In conclusion, despite all progress in non-invasive diagnostic procedures for metabolic bone diseases such as osteoporosis, there remains a small but significant subset of patients who may benefit from inclusion of bone biopsy into the diagnostic procedure.

Giant cell tumor (GCT) offers a unique model for the hematopoietic-stromal cell interaction in human bone marrow. Evidence has been presented that GCT stromal cells (GCTSCs) promote accumulation, size and activity of the giant cells. Although GCTSCs are considered the neoplastic component of GCT, little is known about their genetic basis and, to date, a tumor-specific gene expression pattern has not been characterized. Mesenchymal stem cells (MSCs) have been identified as the origin of the GCT neoplastic stromal cell. Using state of the art array technology, expression profiling was applied to enriched stromal cell populations from five different GCTs and two primary MSCs as controls. Of the 29 differentially expressed genes found, 25 showed an increased expression. Differential mRNA expression was verified by real-time polymerase chain reaction analysis of 10 selected genes, supporting the validity of cDNA arrays as a tool to identify tumor-related genes in GCTSCs. Increased expression of two oncogenes, JUN and NME2, was substantiated at the protein level, utilizing immunohistochemical evaluation of GCT sections and Western-blot analysis. Increased phosphorylation of JUN Ser-63 was also found.

Resorption lacunae and perforation types mirror resorptional activity of osteoclasts and are important for the integrity of bone architecture. In the present study, distinctive microstructural features of cancellous bone dissected from femoral heads of 28 autopsy subjects (14 females and 14 males) were defined and evaluated by light microscopic (LM) histology and scanning electron microscopy (SEM). The work differentiates two types of resorption lacunae in trabecular bone: the longitudinally extended resorption lacunae (LER) and the reticulate patch resorption lacunae (RPR). Further, two types of perforations are distinguished: the lacunar perforation (LP) and the tunneling perforation (TP), which are differentiated from potential blood vessel canals (BC). Evidence is presented that the spatial distribution on rods or plates is highly correlated with the resorption type. The RPR type was more frequently seen and was primarily localized at the nodes of rods, in the middle regions of rods, and in the center region of plates as compared to the LER type. The presented evaluation scheme of resorption and perforation types could prove useful in future studies for systematically investigating potential microstructural changes associated with disturbed bone turnover.

The purpose of this study was to quantify the heterogeneity in the trabecular bone structure in the calcaneus. Magnetic resonance (MR) images of the calcaneus were obtained in the sagittal plane at an in-plane resolution of 195 microns and a slice thickness of 1000 microns in 12 young normal subjects. Regions of interest (ROI) were selected to cover the calcaneus using a grid of square boxes (10 mm per side). A thresholding technique based on the regional intensity histogram was used to segment the images into trabecular bone and marrow phases and to calculate measures such as apparent trabecular bone area fraction, apparent trabecular spacing, apparent trabecular thickness and apparent trabecular number. Bone mineral density (BMD) of the calcaneus was assessed using dual-energy X-ray absorptiometry (DXA). Histological sections of three calcanei were also analyzed using transmission light illumination, and the results used to calibrate our computational software. For a relatively narrow inter-subject variation in posterior BMD, a significant inter-subject variation was seen in MRI-derived structural parameters. Furthermore, the spatial heterogeneity of the structural parameters in the posterior region was as high as 40%. Thus, the posterior tuberosity of the calcaneus, a typical site for BMD and single-point ultrasound assessments, can demonstrate significant regional variation in trabecular bone structure.