acid-phosphatase and Osteosarcoma

Initial studies indicated that bone and cartilage, when treated with a hypertonic glutaraldehyde fixative for a short period, retained significant enzyme activity for histochemistry and also maintained excellent fine structure. We used 6% glutaraldehyde in 0.1 M cacodylate buffer, pH = 7.2, 4 degrees C to fix small pieces of bone or cartilage for three hours while the tissues were being constantly agitated. These samples were demineralized in 10% ethylene diamine tetraacetic acid, buffered to pH = 7.2 with 0.1 M Tris HC1, at 4 degrees C. The demineralized tissue was frozen and cryostat sections 32 microns thick were taken for incubation at 37 degrees C in various media for histochemistry. For electron microscopic localization of enzymes a heavy metal capturing method had to be used. For light microscopy, the azo dye methods were frequently used, but these were not usable for electron microscopy. Alkaline phosphatase was found on the outer surface of osteoblast and hypertrophic cartilage cell membranes. The only intracellular enzyme activity was found on the mitochondrial membranes of the osteoclast and only when the pH of the media was lowered from the optimum 9.5 to 8.5. Alkaline phosphatase was not found along the osteocyte or young cartilage cell membranes...

Topics: Acid Phosphatase; Alkaline Phosphatase; Bone and Bones; Bone Neoplasms; Cartilage; Cartilage Diseases; Cell Membrane; Giant Cell Tumors; Golgi Apparatus; Histocytochemistry; Humans; Lysosomes; Mucolipidoses; Organoids; Osteoblasts; Osteoclasts; Osteocytes; Osteogenesis Imperfecta; Osteosarcoma; Phosphoric Monoester Hydrolases

Bone deposition and bone resorption are ongoing dynamic processes, constituting bone remodeling. Some bone tumors, such as osteosarcoma (OS), stimulate focal bone deposition. OS is the most common primary bone tumor in children and young adults. A complex network of genes regulates bone remodeling and alterations in its expression levels can influence the genesis and progression of bone diseases, including OS. We hypothesized that the expression profiles of bone remodeling regulator genes would be correlated with OS biology and clinical features. We used real-time PCR to evaluate the mRNA levels of the tartrate-resistant acid phosphatase (ACP5), colony stimulating factor-1 (CSF1R), bone morphogenetic protein 7 (BMP7), collagen, type XI, alpha 2 (COL11A2), and protein tyrosine phosphatases zeta 1 (PTPRZ1) genes, in 30 OS tumor samples and correlated with clinical and histological data. All genes analyzed, except CSF1R, were differentially expressed when compared with normal bone expression profiles. In our results, OS patients with high levels of COL11A2 mRNA showed worse overall (p = 0.041) and event free survival (p = 0.037). Also, a trend for better overall survival was observed in patients with samples showing higher expression of BMP7 (p = 0.067). COL11A2 overexpression and BMP7 underexpression could collaborate to OS tumor growth, through its central role in bone remodeling process.

Topics: Acid Phosphatase; Adolescent; Biopsy; Bone Morphogenetic Protein 7; Bone Neoplasms; Bone Resorption; Calcification, Physiologic; Child; Collagen Type XI; Disease Progression; Female; Gene Expression Regulation, Neoplastic; Humans; Isoenzymes; Male; Osteosarcoma; Receptor-Like Protein Tyrosine Phosphatases, Class 5; Receptor, Macrophage Colony-Stimulating Factor; RNA, Messenger; Survival Analysis; Tartrate-Resistant Acid Phosphatase; Young Adult

Osteosarcoma (OS) is the most common primary malignant bone tumour, and mainly affects adolescents and young adults. Although there has been substantial improvement in management of OS with surgery and chemotherapy, further survival increase has not been achieved over the past two decades.. We focused on the receptor activator of nuclear factor kappaB ligand (RANKL)-osteoclast (OCL) system as a biological target for OS. RANKL is a critical factor for OCL formation and bone resorption activity. The primary lesion in bone and ensuing metastasis in OS both require the induction of OCLs. RANK-Fc is a potent RANKL antagonist and inhibitor of OCL formation and activity.. In an orthotopic model in Balb/c nu/nu mice, a twice weekly dosing regimen of 350 microg of RANK-Fc per mouse subcutaneously (n= 5) reduced lung metastasis (P > 0.05), preserved bone structure and reduced tartrate-resistant acid phosphatase (TRAP)(+) OCLs (P < 0.005) in OS-bearing bone. In vitro, RANK-Fc suppressed OCL formation (P < 0.005), bone resorption activity (P < 0.005) and RANKL-induced anti-apoptosis (P < 0.5) of OCLs.

Topics: Acid Phosphatase; Animals; Apoptosis; Bone and Bones; Bone Neoplasms; Bone Resorption; Disease Models, Animal; Humans; Isoenzymes; Lung Neoplasms; Male; Mice; Mice, Inbred BALB C; Mice, Knockout; Osteoclasts; Osteosarcoma; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Recombinant Fusion Proteins; Tartrate-Resistant Acid Phosphatase

We conducted a transcriptomic screen of osteosarcoma (OS) biopsies and found that expression of osteoclast-specific tartrate-resistant acid phosphatase 5 (ACP5/TRAP) is significantly downregulated in OS compared with nonmalignant bone (P < 0.0001). Moreover, lesions from OS patients with pulmonary metastases had 2-fold less ACP5/TRAP expression (P < 0.018) than lesions from patients without metastases. In addition, we found a direct correlation (P = 0.0166) between ACP5/TRAP expression and time to metastasis. Therefore, we examined whether metastasis-competent (MC) OS cells could induce loss of ACP5(+) osteoclasts and contribute to metastasis. We found that MC OS cell lines can inhibit osteoclastogenesis in vitro and in vivo. In addition, osteoclasts can inhibit the migration of MC OS cells in vitro. Finally, ablation of osteoclasts with zoledronic acid increases the number of metastatic lung lesions in an orthotopic OS model, whereas fulvestrant treatment increases osteoclast numbers and reduces metastatic lesions. These data indicate that the metastatic potential of OS is determined early in tumor development and that loss of osteoclasts in the primary lesion enhances OS metastasis.

Topics: Acid Phosphatase; Adolescent; Adult; Aged; Animals; Biopsy; Bone Neoplasms; Child; Female; Humans; Isoenzymes; Lung Neoplasms; Male; Mice; Mice, Inbred BALB C; Middle Aged; Osteoclasts; Osteosarcoma; Tartrate-Resistant Acid Phosphatase; Young Adult

Osteosarcoma (OS) is a highly malignant primary skeletal tumor with a striking tendency to rapidly destroy the surrounding bone and metastasize, since metastases are frequently present at clinical onset. The basis for the aggressiveness of this tumor is largely unknown. However, recent studies in in vivo models indicate that the anti-osteolytic drugs, bisphosphonates, can inhibit the tumor local expansion and the formation of metastases. We further investigated the association between the presence of active osteoclasts and the aggressiveness of OS. We evaluated the presence of osteoclasts and the mRNA of different osteoclast-related genes in tumor biopsies from 16 OS patients and in three OS cell lines and the serum levels of bone resorption markers in the same series and in 28 other patients. Tumor-associated osteoclasts were found in 63 and 75% of cases by histological and mRNA analysis. Among different serum markers, only MMP-9 was significantly higher in OS cases (p=0.0001), whereas TRACP 5b was significantly higher in metastatic patients compared to nonmetastatic patients (p=0.0509). Serum TRACP 5b was significantly correlated to serum NTX (p<0.0001) and cathepsin K mRNA in tumor tissues (p=0.0153). In 8 patients we also analyzed TRACP 5b serum level at follow-up and we verified a significant decrease of TRACP 5b after primary tumor removal (p=0.0117). In conclusion, tumor-infiltrating osteoclasts are frequently found in OS and increased serum TRACP 5b levels and the presence of active osteoclast at primary sites were positively associated with tumor aggressiveness.

Topics: Acid Phosphatase; Adolescent; Adult; Biomarkers; Bone Neoplasms; Bone Resorption; Case-Control Studies; Cathepsin K; Cathepsins; Cell Differentiation; Cell Line, Tumor; Child; Child, Preschool; Collagen Type I; Female; Gene Expression Regulation, Neoplastic; Humans; Interleukin-6; Isoenzymes; Macrophage Colony-Stimulating Factor; Male; Matrix Metalloproteinase 9; Neoplasm Invasiveness; Osteoclasts; Osteosarcoma; Parathyroid Hormone-Related Protein; Peptides; RANK Ligand; Receptor, Parathyroid Hormone, Type 1; RNA, Messenger; Tartrate-Resistant Acid Phosphatase; Time Factors; Young Adult

To detect the expression of multidrug resistance-associated protein 1 (MRP1) in human ostesarcoma and to explore its relationship with clinicopathologic characteristics.. Six normal bone specimens and 45 osteosarcomas from patients were analysed for MRP1 expression by immunohistochemistry. The expression levels of MRP1 with the clinicopathologic parameters of the patients were examined using Chisquare test.. The expression of MRP1 was observed in 32 (71.11%) osteosarcoma specimens. More(P < 0.05) specimens expressed MRP1 in high-grade osteosarcomas(30/38, 78.95%) than in low-grade osteosarcomas (2/7, 28.57%). The correlation coefficient between expression of MRP1 and grade of pathology was 0.844. In a limited number of patients, the expression of MRP1 was not related to the the age and sex of the patients, Enneking surgical stage, osteosarcoma size, serum concentration of ALP and duration before diagnosis. No expression of MRP1 in 6 normal bone specimens was observed.. MRP1 is expressed in osteosarcoma and its expression is positively correlated with the malignancy of osteosarcoma.

Topics: Acid Phosphatase; Adolescent; Adult; ATP Binding Cassette Transporter, Subfamily B, Member 1; Bone Neoplasms; Child; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Female; Humans; Immunohistochemistry; Male; Middle Aged; Osteosarcoma

When monocytes were cocultured with human osteosarcoma-derived cells (HOS cells), multinucleated giant cell formation of monocytes was induced. Intriguingly, even when a filter was interposed between monocytes and HOS cells, polykaryocytes also appeared. The multinucleated giant cells have characters similar to osteoclast-like cells. These findings indicate that soluble factor(s) secreted from HOS cells play an important role in polykaryocyte formation from monocytes. Twelve cloned cells were established from HSOS-1 cells and their capacities of inducing osteoclasts were investigated. Three cloned cells inducing nos. 4 and 9 had an ability of inducing osteoclasts (multinucleated giant cells, TRAP, calcitonin receptor and c-src mRNAs, osteoresorbing activity), and three cells, including nos. 1 and 5, did not show the ability. HOS cells and the cloned cells expressed several cytokine mRNAs. M-CSF was detected in the culture fluids of HOS cells, which also expressed RANK and RANK/ODF/OPGL mRNAs. Intriguingly, HOS cells secreting a soluble osteoclast inducing factors(s) expressed TNF-alpha converting enzyme mRNA. Furthermore, OCIF/OPG inhibited HOS cell-induced osteoclastogenesis and soluble RANKL could be detected in the culture fluids of HOS cells expressing TACE, suggesting that one of soluble osteoclast-inducing factor(s) is soluble RANKL. When blood monocytes were indirectly cocultured with HSOS-1 cells or cloned no. 9 cells in the presence of OCIF for 14 days, HOS cell-mediated osteoclastogenesis was suppressed, indicating that RANK-RANKL system is involved in the HOS cell-mediated osteoclastogenesis.

Topics: Acid Phosphatase; Adolescent; Animals; Biological Factors; Bone Neoplasms; Bone Resorption; Cell Differentiation; Cell Fusion; Cell Line; Child; Clone Cells; Coculture Techniques; Coloring Agents; DNA, Complementary; Electrophoresis, Polyacrylamide Gel; Female; HeLa Cells; Humans; Isoenzymes; Mice; Monocytes; Osteoclasts; Osteosarcoma; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Tartrate-Resistant Acid Phosphatase; Tumor Cells, Cultured

We cloned the human tartrate-resistant acid phosphatase (TRAP) gene from human osteosarcoma cells (Saos-2), and produced recombinant human TRAP (rhTRAP) using a baculovirus vector expression system. RhTRAP from Sf9 culture medium was purified by cation exchange chromatography, gel filtration and affinity chromatography. The molecular mass and amino acid composition of the rhTRAP were consistent with the deduced amino acid composition from the TRAP gene. The N-terminal amino acid sequence of rhTRAP was identical to that of TRAP purified from osteoclastoma and hairy cell leukemia spleen. The monoclonal antibodies generated against rhTRAP also reacted to human placental TRAP (pTRAP). The optimum pH of rhTRAP and pTRAP were pH 5.0-5.5 and pH 6.0-6.5, respectively. The enzymatic activities of rhTRAP and pTRAP were activated by reducing agents such as 2-mercaptoethanol, dithiothreitol and ascorbic acid. The activities of rhTRAP and pTRAP were enhanced by Fe2+ ions, but were inhibited by Fe3+ ions. The present results indicate that rhTRAP has similar properties to the native human TRAP, and suggest that the enhancement of TRAP activity by reducing agents might be expressed via the reduction of Fe ions at the metal center.

Topics: Acid Phosphatase; Adult; Amino Acids; Animals; Antibodies, Monoclonal; Base Sequence; Bone Neoplasms; Cell Line; Cloning, Molecular; Enzyme-Linked Immunosorbent Assay; Female; Humans; Hydrogen-Ion Concentration; Insecta; Isoenzymes; Mice; Mice, Inbred BALB C; Osteosarcoma; Placenta; Pregnancy; Recombinant Proteins; Reducing Agents; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Tartrate-Resistant Acid Phosphatase

Subclones of the human osteosarcoma cell line SaOS-2 were established by transfecting with an expression vector containing the human PTH/PTH-related protein (PTHrP) receptor, and their abilities to support osteoclast-like multinucleated cell (OCL) formation were examined in coculture with mouse or human hemopoietic cells. Of four subclones examined, SaOS-2/4 and SaOS-4/3 bound high levels of [125I]-PTH and produced a significant amount of cAMP in response to PTH. OCLs were formed in response to PTH in the cocultures of mouse bone marrow cells with either SaOS-2/4 cells or SaOS-4/3 cells. Human OCLs were also formed in response to PTH in the coculture of SaOS-4/3 cells and human peripheral blood mononuclear cells. Adding dexamethasone together with PTH greatly enhanced PTH-induced human OCL formation. Like mouse OCLs, human OCLs formed in response to PTH were tartrate-resistant acid phosphatase positive, expressed abundant calcitonin receptors and vitronectin receptors, and formed resorption pits on dentine slices. Other osteotropic factors such as 1alpha,25-dihydroxyvitamin D3, prostaglandin E2, and interleukin 6 plus soluble interleukin 6 receptors failed to induce mouse and human OCLs in cocultures with SaOS-4/3 cells. Both mouse and human OCL formation supported by SaOS-4/3 cells were inhibited by either adding an antibody against macrophage-colony stimulating factor or adding granulocyte/macrophage-colony stimulating factor. Thus, it is likely that human and mouse OCL formation supported by SaOS-4/3 cells are similarly regulated. These results indicate that the target cells of PTH for inducing osteoclast formation are osteoblast/stromal cells but not osteoclast progenitor cells in the coculture. This coculture model will be useful for investigating the abnormalities ofosteoclast differentiation and function in human metabolic bone diseases.

Topics: Acid Phosphatase; Animals; Bone Marrow Cells; Cell Differentiation; Coculture Techniques; Dexamethasone; Drug Synergism; Glucocorticoids; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Isoenzymes; Macrophage Colony-Stimulating Factor; Mice; Monocytes; Osteoclasts; Osteosarcoma; Parathyroid Hormone; Receptor, Parathyroid Hormone, Type 1; Receptors, Parathyroid Hormone; Tartrate-Resistant Acid Phosphatase; Transfection; Tumor Cells, Cultured

The antitumor effect of intra-tumoral injection of Cepharanthin, a biscoclaurin alkaloid extracted from Stephania cephalanta Hayata, and staphylococcal enterotoxin B was evaluated using F344 male rats bearing transplantable rat osteosarcoma, S-SLM. A macroscopic lung metastatic nodule of tumor was transplanted into the subcutaneous back space, and 0.5 mg of Cepharanthin and 2 pg of staphylococcal enterotoxin B were injected into the tumor on days 12, 13 and 14. On day 28, all animals were killed with an overdose of pentobarbital sodium, and the transplanted tumors and lungs were examined. The wet weight of the lungs of the rats treated with Cepharanthin and staphylococcal enterotoxin B was significantly lower, and apoptosis in the lung metastatic nodules was significantly higher than that of the control or that of rats treated with only Cepharanthin or staphylococcal enterotoxin B. In the transplanted tumors, infiltration of TRAP (tartrate-resistant acid phosphatase)-positive multinucleated giant cells was prominent in the rats treated with Cepharanthin and staphylococcal enterotoxin B. These findings indicate that intra-tumoral injection of Cepharanthin and staphylococcal enterotoxin B induced infiltration of TRAP-positive multinucleated giant cells within the transplanted rat osteosarcoma, and reduced lung metastasis.

Topics: Acid Phosphatase; Alkaloids; Animals; Antineoplastic Combined Chemotherapy Protocols; Benzylisoquinolines; Enterotoxins; In Situ Nick-End Labeling; Isoenzymes; Lung Neoplasms; Male; Neoplasm Transplantation; Organ Size; Osteosarcoma; Rats; Rats, Inbred F344; Tartrate-Resistant Acid Phosphatase

To study the effects of osteoblast products on osteoclast formation, we added the conditioned medium (CM) of rat osteoblastic cell line ROS17/2.8 to rat bone marrow cultures, in which tartrate-resistant acid phosphatase (TRAP)-positive osteoclast-like multinucleate cells (MNCs) formed in the presence of 10(-8) M 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). The formation of 1,25(OH)2D3-dependent TRAP-positive MNC at day 7 of culture was strongly inhibited by the > 10 kDa fraction of ROS17/2.8 cell-CM (ROSCM), but heat treated ROSCM (htROSCM) expressed marked stimulation in the formation of the MNCs. The expression of several osteoclastic phenotypes of the MNCs induced by htROSCM and 1,25(OH)2D3 was more enhanced compared with that of the MNCs induced by 1,25(OH)2D3 alone. The MNCs induced by htROSCM and 1,25(OH)2D3 were highly motile, were sensitive to calcitonin (CT), and had high bone resorbing activity. These data suggest that htROSCM promotes the osteoclast differentiation in the presence of 1,25(OH)2D3 in a rat bone marrow culture system. The stimulatory activity of TRAP-positive MNC formation in htROSCM is derived from heat-stable protein(s) that is (are) thought to be different from colony-stimulating factors (CSFs) such as macrophage-CSF (M-CSF) or granulocyte-macrophage-CSF (GM-CSF).

Topics: Acid Phosphatase; Animals; Bone Marrow; Bone Marrow Cells; Bone Neoplasms; Bone Resorption; Calcitonin; Calcitriol; Cell Differentiation; Cell Movement; Cells, Cultured; Culture Media, Conditioned; Dentin; Hot Temperature; Male; Osteoblasts; Osteoclasts; Osteosarcoma; Phenotype; Rats; Rats, Sprague-Dawley; Receptors, Calcitriol; Time Factors; Tumor Cells, Cultured

A tartrate-resistant acid phosphatase (TrACP), which has been suggested to be very similar to the osteoclastic TrACP, was partially purified from the spleen of a patient with hairy cell leukemia. The purification procedure consisted of carboxymethyl-Sepharose, phosphocellulose, Sephacryl S-200, and phenyl-Sepharose chromatographies. Polyclonal antibodies were generated in guinea pigs with a titer of at least 1:6000. Immunohistochemical staining of fetal rat tibia with the antisera revealed that only the lysosomes of osteoclasts, but not osteoblasts, were stained. An enzyme-linked immunosorbent assay (ELISA) was developed with the antisera. There was no cross-reactivity with 1) partially purified acid phosphatases (ACPs) from normal human and beef spleens, 2) ACPs in extracts of human osteoblastic cells, 3) purified bovine bone matrix TrACP, or 4) commercial prostatic ACP. However, extracts of giant cell bone tumors, containing large amounts of bona fide osteoclasts, showed large amounts of cross-reactive material, which diluted in parallel with the partially purified hairy cell leukemic TrACP in the ELISA. Commercial serum band 5b TrACP also displaced in parallel with the partially purified hairy cell leukemic TrACP. Immunoblotting studies revealed that the antiserum, but not nonimmune guinea pig serum, reacted with the homogeneous hairy cell leukemia splenic band 5 TrACPs, which were recently purified by our laboratory. Preliminary application of the ELISA to sera of patients with metabolic bone diseases revealed that normal healthy individuals had measurable amounts of the immunoreactive material, and patients with Paget's disease or hyperparathyroidism, who should have high bone turnover, had elevated levels of this immunoreactive material in their sera. In contrast, the level of serum osteoclastic TrACP in a patient with an acute lymphatic leukemia was normal. In summary, 1) we have shown that hairy cell leukemia splenic TrACP shares significant immunological similarity with the osteoclastic TrACP and with the serum band 5b TrACP, and 2) the ELISA holds promise for a sensitive and specific assay for bone resorption.

Topics: Acid Phosphatase; Animals; Bone Neoplasms; Chromatography, Affinity; Chromatography, Ion Exchange; Cross Reactions; Electrophoresis, Polyacrylamide Gel; Enzyme-Linked Immunosorbent Assay; Histocytochemistry; Humans; Isoenzymes; Leukemia, Hairy Cell; Osteoblasts; Osteoclasts; Osteosarcoma; Rats; Spleen; Tartrates; Tumor Cells, Cultured

1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) is known to interact in vitro with mononuclear phagocytes. The purpose of this study was to determine the role of the steroid in macrophage activation in vivo. Peritoneal macrophages from normal and vitamin D3-deficient mice were obtained after i.p. injection of activating or eliciting agents. Cells obtained from vitamin D3-deficient mice exhibited defected capabilities to perform anti-tumor activities (cytostasis and cytolysis) and to form oxygen reduction products (H2O2 and O2-). On the other hand, the level of the lysosomal enzyme acid phosphatase was unaffected by vitamin D3 deficiency. In vitro, incubation of macrophages with 1,25(OH)2D3 enhanced their anti-tumor activities, but did not affect the cells' capacity to produce H2O2 and O2-, or acid phosphatase. Our results suggest that 1,25(OH)2D3 is essential for macrophage activation in vivo. However, in vitro, the hormone is only partially capable of affecting the macrophage functions, probably because of the maturation state of the cells.

Topics: Acid Phosphatase; Animals; Calcitriol; Cells, Cultured; Macrophage Activation; Macrophages; Male; Mice; Mice, Inbred BALB C; Osteosarcoma; Oxygen Consumption; Peritoneal Cavity; Tumor Cells, Cultured; Vitamin D Deficiency

Osteosarcoma in the metaphysis to epiphysis of the left femur of a 17-year-old male is reported. The lesion appeared osteolytic with sclerotic foci on roentgenographs, accompanied by an extensive tumor shadow in the surrounding soft tissue. While 60% of the tumor was necrotic, histological examination of the remaining viable tissue revealed that it consisted almost entirely of a sheet of epithelioid cells, separated by thin, fibrovascular septa with an alveolar-like pattern, suggestive of metastatic carcinoma. Only a few areas were characterized by malignant osteoid tissue intermingled with the above cells, showing significant positivity for bone-specific alkaline phosphatase and 5'-nucleotidase, thus permitting a diagnosis of osteosarcoma. Autopsy findings revealed that the metastatic foci were histologically similar to those of the primary tumor. Electron microscopy revealed poor development of cytoplasmic organelles, supporting possible derivation from an osteoblastic cell lineage at an early stage.

Topics: Acid Phosphatase; Adolescent; Alkaline Phosphatase; Bone Neoplasms; Carcinoma; Epithelium; Humans; Male; Osteosarcoma; Prognosis

In osteoclastic giant cells of six different tumors of bones and joints (fibrous dysplasia, proliferating giant cell tumor, malignant giant cell tumor, osteosarcoma after chemotherapy, malignant synovioma and Ewing's sarcoma) activities of tartrate-resistant acid phosphatase, NADH-tetrazolium-oxidoreductase and, in three of them, of non-specific esterase are determined by enzyme histochemical methods. Quantitative microphotometry makes it possible to determine relative enzyme activities in the cut sections of giant cells of different sizes. Giant cells of the various tumors reveal similar trends: With an increase in cell size, mean extinctions of NADH-tetrazolium-oxidoreductase and non-specific esterase decrease. Mean extinctions of tartrate-resistant acid phosphatase increase in cells of medium size, whereas the large cells reveal in part low activities. An additional ultrastructural examination of the giant cells in the proliferating giant cell tumor as well as in the osteosarcoma shows morphological signs of degeneration in the large cells. Electron probe microanalysis of the proliferating giant cell tumor exhibits evidence of phagocytosis of Ca and/or Fe containing particles. The similar size dependent reaction pattern of enzymes in osteoclastic giant cells of different tumors favors the concept of a common histogenesis, i.e. a host reaction.

Topics: Acid Phosphatase; Bone Neoplasms; Carboxylesterase; Carboxylic Ester Hydrolases; Fibrous Dysplasia of Bone; Giant Cell Tumors; Humans; NADH Tetrazolium Reductase; Osteoclasts; Osteosarcoma; Sarcoma, Ewing; Sarcoma, Synovial

Topics: Acid Phosphatase; Adolescent; Antineoplastic Agents; Bone Neoplasms; Child; Combined Modality Therapy; Humans; Hyperthermia, Induced; Osteosarcoma

A new technique was applied to the study of human osteosarcoma. Ten slices of 10 micron were cut serially from 2 X 2 X 6 mm shock frozen blocks of human osteosarcoma for chemical analysis. Before and after each series of 10 slices, one slice of 10 micron was separated for morphological analysis. Four different types of osteosarcoma were investigated: Case 1 was an atypical osteoblastic osteosarcoma, case 2 a small cell sclerosing osteosarcoma, case 3 a well-differentiated parosteal osteosarcoma grade I, and case 4 a highly malignant anaplastic osteosarcoma. Alkaline phosphatase, acid phosphatase, beta-glucuronidase and proteolytic activities were analysed as well as matrix collagen and hexosamine, phosphorus (Pi and Po), protein, DNA, and water content. In accordance with the morphology, the obtained data illustrate the great heterogeneity of osteosarcomas. Although case 1, 2 and 3 all represent calcifying types of the tumor, characteristic differences exist with regard to the matrix and the degree of calcification. In contrast to these three, case 4 presents a noncalcified type of osteosarcoma whose matrix contains relatively high amounts of hexosamine and low amounts of collagen, whereas DNA and water contents are high. The data from the analysis of osteosarcoma were compared with previous results from the calf epiphyseal growth plate in order to define differences and similarities between the formation of tumor bone and the physiological formation of hard tissue.

Topics: Acid Phosphatase; Alkaline Phosphatase; Bone Neoplasms; Glucuronidase; Humans; Osteosarcoma; Registries

Human osteosarcoma specimens were sliced in a cryomicrotome under strict morphological guidance. Serial sections of ten 10 micron slices each were collected in two groups according to morphologic criteria, one containing mostly undifferentiated tumor tissue, the other predominantly well-differentiated tumor tissue. The two series were analysed chemically for alkaline phosphatase (APase) acid phosphatase (acPase), beta-glucuronidase and proteolytic activities; protein, phosphorus, hydroxyproline, hexosamine, water and collagen contents were also determined. Four different types of osteosarcoma were studied: case 1 was a highly malignant osteoblastic osteosarcoma, case 2 a small cell sclerosing osteosarcoma case 3 a well-differentiated osteosarcoma, and case 4 a highly malignant anaplastic osteosarcoma. The types of cases 1, 2 and 3 are known as osteoid-forming tumors. In their less well differentiated areas APase activity was about twice as high as in better differentiated osteosarcoma. In contrast, no APase was found in the wholly undifferentiated areas of case 4, while the enzyme showed a marked increase in the areas of incipient differentiation of this tumor. The matrix of tumors differs with regard to collagen and hexosamine contents, in accordance with the general state of differentiation. In general, increasing hexosamine contents together with decreasing hydroxyproline contents will reflect the anaplastic, dedifferentiated osteosarcoma. Calcification evident in the better differentiated areas of osteosarcoma is indicated by the phosphorus content, highest in case 2, with cases 3, 1, and 4 following in sequential order.

Topics: Acid Phosphatase; Alkaline Phosphatase; Bone Neoplasms; Collagen; Glucuronidase; Hexosamines; Humans; Hydroxyproline; Neoplasm Proteins; Osteosarcoma; Peptide Hydrolases

The clonal cell line UMR 106, which was originally derived from a rat transplantable osteogenic sarcoma with an osteoblastic phenotype, was subcloned after the emergence of a calcitonin-responsive adenylate cyclase was noted in late passages. Detailed studies on the stimulation of adenylate cyclase and activation profile of the cyclic AMP-dependent protein kinase isoenzymes in response to parathyroid hormone (PTH) and salmon calcitonin (SCT) were conducted on two subclones (UMR 106-01 and UMR 106-06). Both subclones responded in an identical manner to PTH, which stimulated adenylate cyclase and activated both isoenzyme I and isoenzyme II of cyclic AMP-dependent protein kinase. In contrast, only UMR 106-06 cells responded to calcitonin. At 3 X 10(-8)M SCT, there was a sevenfold stimulation of adenylate cyclase, 84% activation of isoenzyme I, and 44% activation of isoenzyme II. The activation profiles of the isoenzymes to PTH and SCT in UMR 106-06 were similar. Furthermore, their response to SCT correlates with the presence of specific, saturable binding of 125I-labeled SCT. Binding parameters indicate apparent Kd = 0.8 nM and 6,000 receptors/cell. These data point to a significant phenotypic change having taken place in this clonal cell line with prolonged maintenance in culture, with the emergence of a calcitonin receptor linked to adenylate cyclase and protein kinase activation.

Topics: Acid Phosphatase; Adenylyl Cyclases; Alkaline Phosphatase; Animals; Calcitonin; Cell Line; Clone Cells; Enzyme Activation; Isoenzymes; Osteoblasts; Osteosarcoma; Parathyroid Hormone; Phenotype; Protein Kinases; Rats

Topics: Acid Phosphatase; Adolescent; Adult; Aged; Bone Neoplasms; Child; Chondroma; Chondrosarcoma; Diagnosis, Differential; Female; Fibrosarcoma; Giant Cell Tumors; Histiocytoma, Benign Fibrous; Humans; Lymphoma; Male; Middle Aged; Osteosarcoma

The ultrastructural and biochemical properties of four clonal osteogenic sarcoma lines, UMR 104, 105, 106, and 108, have been compared with uncloned osteogenic sarcoma cells and normal osteoblast-rich cells derived from newborn rat calvaria. High alkaline phosphatase activity and activation of adenylate cyclase by parathyroid hormone were used as biochemical markers of osteoblastic cells. Cloning enriched both of these parameters above those of the parent tumor and far higher than that seen in normal cells, suggesting enrichment of the osteoblast phenotype. Both of these properties have been retained through many passages in culture. Morphologically, the clonal lines have also retained the "blast"-like appearance of the uncloned osteogenic sarcoma cells and consist mainly of flat, relatively featureless cells. Many cells with mitotic figures were observed, indicating continuous cell division taking place in the malignant cells. Each clonal line gave rise to characteristic tumors when reinjected into rats. It is concluded that the clonal osteogenic sarcoma lines are highly differentiated tumor lines which have conserved the differentiated properties of the mature osteoblast, making them a suitable model for the study of the effects of hormones on the growth of a differentiated tumor, as well as for the study of hormonal regulation of the osteoblast.

Topics: Acid Phosphatase; Adenylyl Cyclases; Alkaline Phosphatase; Animals; Calcitonin; Cell Line; Clone Cells; Dinoprostone; Enzyme Activation; Kinetics; Microscopy, Electron; Osteosarcoma; Parathyroid Hormone; Prostaglandins E; Rats; Sarcoma, Experimental

Twelve osteosarcomas treated according to the COSS 80 protocol (preoperative chemotherapy, resection) were studied by light and electron microscopic, histochemical, and autoradiographic methods. Evidence of regressive and necrotic changes was found in many tumor cells, but the alterations were unspecific. Viable tumor cells of high malignancy were also observed regularly, often at the S phase. As the tumor regression continued, a strong reaction of the mononuclear phagocyte system was manifested by the presence of macrophages and giant cells.

Topics: Acid Phosphatase; Adolescent; Adult; Autoradiography; Bone Neoplasms; Carboxylic Ester Hydrolases; Child; Female; Histocytochemistry; Humans; Macrophages; Male; Microscopy, Electron; Naphthol AS D Esterase; Osteosarcoma

The acid phosphatase in the cells of bone and soft parts tumors, and of other tumorous conditions in our Department of Orthopedic Surgery in Kumamoto University Medical School from mid-1979 through mid-1983 were analysed by light microscopic and electron microscopic histochemical studies and their inhibition studies. The histochemical and their inhibiting studies of acid phosphatase by azo dye method in the cells of bone and soft parts tumors and of other tumorous conditions were undertaken in order to characterize them with a view to providing helpful diagnostic features. The acid phosphatase in some giant cells and tumor cells of several kinds of tumors, whose reaction against inhibitors was different from that of lysosomal acid phosphatase, was observed. In the giant cells of giant cell tumor of bone, acid-para-nitrophenyl phosphatase was demonstrated by the method of Miyayama , et al. using sodium-para-nitrophenyl phosphate as a substrate. In addition, the fine structural localization of acid phosphatase in giant cell tumor of bone was studied by Gomori's method and by the method of Miyayama , et al. By Gomori's method, acid phosphatase activity was demonstrated in lysosome, secondary lysosome-like organelles and the digestive vacuoles in the giant cells. In the stromal cells, that activity was demonstrated in lysosomes. By the method of Miyayama , et al., acid para-nitrophenyl phosphatase was demonstrated in the Golgi complex and the cisternae of the rough endoplasmic reticulum in the giant cell. Therefore, in the giant cells and the tumor cells of some kinds of tumors, non-lysosomal acid phosphatase besides lysosomal acid phosphatase was recognized. The demonstration of non-lysosomal acid phosphatase was a useful tool for the differential diagnosis of tumors and tumorous conditions in bone and soft parts.

Topics: Acid Phosphatase; Bone Neoplasms; Giant Cell Tumors; Histocytochemistry; Humans; Osteosarcoma; Soft Tissue Neoplasms

A total of 19 cases with bone tumors, including six osteosarcomas. three giant cell tumors of bone, one malignant fibrous histiocytoma, four nonossifying fibromas, four chondromas and one chondrosarcoma, were examined as to enzyme histochemistry; the enzymes consisted of alkaline phosphatase (ALPase), acid phosphatase (ACPase), nonspecific esterase (NSE), adenosine triphosphatase (ATPase), 5'-nucleotidase (5'-Nucl) and beta-glucuronidase (beta-Gl). Osteosarcoma was strongly positive for ALPase followed by 5'-Nucl. Giant cell tumor, malignant fibrous histiocytoma and nonossifying fibroma showed enzyme histochemistry similar to each other: multinucleated giant cells and round cells in these tumors were strongly positive for ACPase, NSE, ATPase and 5'-Nucl simulating osteoclasts and histiocytes, whereas spindle cells were positive for ATPase and 5'-Nucl in their cytoplasm and weakly positive for ACPase. Chondroma and chondrosarcoma were focally positive for ACPase and NSE; the ACPase was sensitive to tartaric acid treatment. These observations showed that ALPase activity is very characteristic to osteosarcoma, and is useful for its diagnosis. From enzyme histochemistry, giant cell tumor, malignant fibrous histiocytoma and nonossifying fibroma can be regarded as a histiocyte-derived tumor of bone in contrast to osteosarcoma and cartilaginous tumors.

Topics: Acid Phosphatase; Adenosine Triphosphatases; Adolescent; Adult; Aged; Alkaline Phosphatase; Animals; Bone Neoplasms; Child; Child, Preschool; Chondroma; Chondrosarcoma; Female; Fractures, Bone; Giant Cell Tumors; Histiocytoma, Benign Fibrous; Humans; Male; Metatarsus; Middle Aged; Osteosarcoma; Rabbits; Wound Healing

The morphology of 26 cases of osteogenic sarcoma was studied using electron microscopic techniques, and the localization of acid and alkaline phosphatase activity at the ultrastructural level elucidated. Four different cells were present in the tumours: osteoblast-like, fibroblast-like, chondroblast-like, and multinucleated giant cells. The osteoblast-like cell was present in most of the tumours studied. Acid phosphatase activity was present in lysosome-like structures of almost all the cell-types studied. Alkaline phosphatase activity was noted in or on the plasma membranes and associated vesicles of osteoblast-like, fibroblast-like, and multinucleated giant cells. The abundant reaction product deposition of alkaline phosphatase as compared with the lower acid phosphatase activity is in agreement with the nature of this bone-forming tumour. The results of the histochemical studies have added to the understanding of the pathobiology of the different cells composing osteogenic sarcomas.

Topics: Acid Phosphatase; Alkaline Phosphatase; Bone Neoplasms; Histocytochemistry; Humans; Osteosarcoma

The results of a study of the ultrastructural and enzymatic features of extracellular matrix vesicles in human osteogenic neoplasms are reported. Specimens from three osteosarcomas, a chondrosarcoma, and an osteoblastoma were processed for electron microscopic study and for preparation of vesicular, membrane, and cellular fractions. Electron micrographs of each lesion showed primary mineralization comprised of matrix vesicles and calcifying nodules. There was a distinct pattern of distribution of enzymatic activity among fractions from the osteosarcomas; namely that the highest values for specific activity of alkaline and pyrosphosphatases and adenosine triphosphases (ATPases) in the vesicle fractions and lowest in the cell fractions. This pattern was not consistent in fractions from the other neoplasms. The aforementioned enzymes are considered essential for the onset of mineralization. The data presented establish the role of matrix vesicles in neoplastic calcification and suggest the need for further studies into the diagnostic value of the vesicles.

Topics: Acid Phosphatase; Adenosine Triphosphatases; Adolescent; Adult; Alkaline Phosphatase; Bone Neoplasms; Chondrosarcoma; Extracellular Space; Humans; Middle Aged; Neoplasms, Connective Tissue; Osteoma, Osteoid; Osteosarcoma; Pyrophosphatases

Certain metabolic properties of hormonally responsive osteogenic sarcoma cells derived from a transplantable rat tumor have been compared with those of related normal rat bone cells. All studies were carried out on cells grown in monolayer culture. Normal rat bone cells derived by repeated collagenase/trypsin digestion of newborn rat calvaria. Bone cells selected for comparison were thought to be osteoblast-like, as judged by enrichment of alkaline phosphatase and adenylate cyclase responsiveness to parathyroid hormone and prostaglandin E2. The adenylate cyclases of the two cell strains were similarly stimulated by a range of prostanoids and their metabolites and analogs. Morphology showed the two cell strains to be similar; the only obvious difference was a multilayering of cells in the sarcoma cultures, while the normal cultures showed abundant extracellular fibril formation which was not seen in the tumor cells. Investigation of the cAMP-dependent protein kinase isoenzymes showed the presence of two forms in both cell types, one eluting at a low salt concentration and the other at a high salt concentration. There was approximately twice the amount of the first isoenzyme compared to the second isoenzyme. The results indicate the usefulness of the two cell strains to elucidate further the molecular mechanisms of action of parathyroid hormone and prostaglandins.

Topics: Acid Phosphatase; Adenylyl Cyclases; Alkaline Phosphatase; Animals; Cells, Cultured; Culture Techniques; Osteoblasts; Osteosarcoma; Parathyroid Hormone; Prostaglandins; Protein Kinases; Rats; Sarcoma, Experimental

Topics: Acid Phosphatase; Alkaline Phosphatase; Breast Neoplasms; Clinical Enzyme Tests; Diagnosis, Differential; Dysgerminoma; Female; Humans; L-Lactate Dehydrogenase; Lymphoma; Male; Neoplasm Metastasis; Neoplasms; Osteosarcoma; Succinate Dehydrogenase; Testicular Neoplasms

Topics: Acid Phosphatase; Adolescent; Adult; Arm; Bone Neoplasms; Child; Female; Humans; Hyperbaric Oxygenation; Hypoxia; Leg; Lymphocyte Activation; Male; Osteosarcoma; T-Lymphocytes; Tourniquets

Topics: Acid Phosphatase; Adenylyl Cyclases; Alkaline Phosphatase; Animals; Binding, Competitive; Calcitonin; Calcitriol; Cell Line; Clone Cells; Cytosol; Dihydroxycholecalciferols; Hydroxycholecalciferols; Kinetics; Osteoblasts; Osteosarcoma; Parathyroid Hormone; Prostaglandins E; Rats; Receptors, Calcitriol; Receptors, Steroid

In recent years, histochemistry and electron microscopy have been applied more and more to the investigation of bone tumors. The contributions and limitations of these methods in differential diagnosis are discussed. The levels of glycosaminoglycans in cartilaginous tumors display distinct differences between slow- and fast-growing types. All cartilaginous tumors are poor in phosphatase activity. Demonstration of these enzymes at acid and alkaline pH in bone-forming conditions reveals differences between benign and malignant tumors. Osteosarcomas display a rich activity of both phosphatases in bone-forming and in bone-free regions. Acid phosphatase may play a rôle in the breakdown of the host tissue infiltrated by the tumor. Electron microscopy of bone tumors has brought out some interesting findings. In fibrous dysplasia a particular kind of very fine fibrillar structures was observed besides the regular collagen fibrils. This may indicate retardation of collagen maturation. Cell organelles in benign and malignant bone tumors usually differ quantitatively. They resemble active fibroblasts. In bone- and in cartilage-forming tumors we observed large quantities of microfilaments in the cytoplasm. Nuclear indentations and invaginations probably indicate increased nuclear activity. The intense acid phosphatase activity demonstrated histochemically seems inconsistent with the low number of lysosomes in the cytoplasm of osteosarcoma cells, but other organelles (Golgi apparatus and vesicles) may also contain the enzyme. Virus-like particles have not been observed in human osteosarcomas up to now. Other authors have observed a correlation between the number of cell organelles and the grade of differentiation, but this was not detected in our sample of benign and malignant cartilaginous tumors. Histochemistry and electron microscopy of bone tumors are still in the early stage of material gathering. Some histochemical findings, however, can already be used as diagnostic tools.

Topics: Acid Phosphatase; Alkaline Phosphatase; Bone Neoplasms; Cartilage Diseases; Cell Nucleus; Chondrosarcoma; Collagen; Cytoplasm; Cytoskeleton; Fibrous Dysplasia of Bone; Humans; Osteosarcoma

Topics: Acid Phosphatase; Adolescent; Adult; Bone Neoplasms; Child; Child, Preschool; Female; Fibrosarcoma; Fibrous Dysplasia of Bone; Giant Cell Tumors; Humans; Infant; Isoenzymes; Male; Middle Aged; Osteosarcoma; Sarcoma, Ewing; Soft Tissue Neoplasms

Tumours induced in mice, either CBA normal and chimaerical, or C3H, by (90)Sr or (226)Ra or plutonium have been examined histochemically with (1) diazotate fast red violet LB salt in naphthol AS-MX phosphate buffer at pH 8·6 and 5·2, (2) 1: 9 dimethyl methylene blue (Taylor).It is concluded:(a) The diagnosis of osteosarcoma is facilitated with Taylor's Blue which stains osteoid metachromatically. Cells of osteosarcoma, like normal osteoblasts, contain alkaline phosphatase but this may be lost by mutation either in the original tumour or subsequently on passage of the tumour serially to compatible hosts.(b) Osteosarcomata may contain giant-cells of two forms, bizarre tumour cells and osteoclasts; the latter contain acid phosphatase. Osteosarcomata which retain their osteoid on serial passage have few cells containing acid phosphatases.(c) Primitive mesenchymal cell tumours of angiomatous form may occur, if the bone marrow is irradiated, e.g. by (90)Sr-(90)Y and Pu. These tumours lack osteoid and cells interpretable as osteoblasts or osteoclasts (though they destroy bone).(d) Tumours classifiable as fibrosarcomata occur rarely, and may be truly of fibroblastic origin or be mutated osteosarcomata.(e) Lymphomata also occur when the marrow is irradiated ((90)Sr-(90)Y and Pu). They may be generalized, when their cells may contain alkaline phosphatase or lack it. They may be localized to abdominal viscera, the reticulo-sarcomatous form, in which case the cells lack alkaline phosphatase.

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Clinical Enzyme Tests; Color; Coloring Agents; Fibrosarcoma; Hemorrhage; Histocytochemistry; Lymphoma; Mesenchymoma; Mice; Neoplasms, Experimental; Neoplasms, Radiation-Induced; Osteosarcoma; Phosphoric Monoester Hydrolases; Plutonium; Radiation Dosage; Radioisotopes; Radium; Staining and Labeling; Strontium Radioisotopes; Succinate Dehydrogenase; Yttrium Isotopes

Topics: Acid Phosphatase; Adolescent; Adult; Age Factors; Animals; Animals, Newborn; Antibodies, Neoplasm; Antigens, Neoplasm; Breast Neoplasms; Carcinoma; Cell Line; Child; Child, Preschool; Female; Fluorescent Antibody Technique; Hodgkin Disease; Humans; Infant; Leukemia; Lung Neoplasms; Lysosomes; Male; Melanoma; Microscopy, Electron; Middle Aged; Osteosarcoma; Rats; Sarcoma; Sex Factors; Statistics as Topic

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Extremities; Female; Histocytochemistry; Male; Mandibular Neoplasms; Mice; Neoplasms, Radiation-Induced; Osteoblasts; Osteoclasts; Osteosarcoma; Pelvis; Radium; Ribs; Sacrum; Sarcoma, Experimental; Skull Neoplasms; Spinal Neoplasms; Tail

Topics: Acid Phosphatase; Adult; Alkaline Phosphatase; Bone Neoplasms; Breast Neoplasms; False Positive Reactions; Female; Humans; Iron Isotopes; Lung Neoplasms; Male; Mandibular Neoplasms; Mouth Neoplasms; Neoplasm Metastasis; Osteosarcoma; Pelvic Neoplasms; Pharyngeal Neoplasms; Prostatic Neoplasms; Radionuclide Imaging; Spinal Neoplasms; Strontium Isotopes

Topics: Acid Phosphatase; Adolescent; Adult; Alkaline Phosphatase; Bone Neoplasms; Child; Child, Preschool; Esterases; Female; Femoral Neoplasms; Fibroma; Fibrosarcoma; Fibrous Dysplasia of Bone; Glucuronidase; Humans; Humerus; Hydrolases; Infant, Newborn; Leucyl Aminopeptidase; Male; Mandibular Neoplasms; Middle Aged; Osteosarcoma; Tibia

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Female; Fibroma; Jaw Neoplasms; Male; Mice; Neoplasms, Radiation-Induced; Osteosarcoma; Pathology; Radioisotopes; Radium; Sarcoma, Experimental; Thorium

Topics: Acid Phosphatase; Alkaline Phosphatase; Bone Neoplasms; Histocytochemistry; Humans; Lymphoma, Large B-Cell, Diffuse; Osteosarcoma; Sarcoma, Ewing

Topics: Acid Phosphatase; Alkaline Phosphatase; Bone Neoplasms; Chondroma; Chondrosarcoma; Diagnosis, Differential; Giant Cell Tumors; Hemangiosarcoma; Histocytochemistry; Humans; Lymphoma, Large B-Cell, Diffuse; Methods; Osteoma, Osteoid; Osteosarcoma; Sarcoma, Ewing; Sarcoma, Synovial

Topics: Acid Phosphatase; Adolescent; Adult; Alkaline Phosphatase; Chondrosarcoma; Giant Cell Tumors; Glucosephosphate Dehydrogenase; Histocytochemistry; Humans; Isocitrate Dehydrogenase; Jaw Neoplasms; Male; NADP; Osteosarcoma; Succinate Dehydrogenase

Topics: Acid Phosphatase; Adenosine Triphosphatases; Alkaline Phosphatase; Animals; Histocytochemistry; Mice; Neoplasm Transplantation; Neoplasms, Experimental; Osteosarcoma

Topics: Acid Phosphatase; Adolescent; Alkaline Phosphatase; Bone Neoplasms; Carboxylesterase; Child; Chondroblastoma; Chondroma; Chondrosarcoma; Coloring Agents; Esterases; Fibroma; Fibrosarcoma; Fibrous Dysplasia of Bone; Geriatrics; Giant Cell Tumors; Glucuronidase; Histocytochemistry; Histological Techniques; Humans; Osteosarcoma; Pathology; Phosphoric Monoester Hydrolases; Sarcoma, Synovial; Staining and Labeling

Topics: Acid Phosphatase; Adenoma; Alkaline Phosphatase; Ameloblastoma; Arthritis; Bone Cysts; Bone Neoplasms; Chondrosarcoma; Fibroma; Fibrous Dysplasia of Bone; Geriatrics; Giant Cell Tumors; Humans; Neoplasm Metastasis; Osteitis Fibrosa Cystica; Osteoma; Osteosarcoma; Prognosis; Radiography; Sarcoma, Ewing; Tuberculosis; Tuberculosis, Osteoarticular