Cases reported "Bone Resorption"

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1/21. Study of the cell biology and biochemistry of cherubism.

    AIMS: To establish whether the multinucleate cells in lesions of patients with cherubism are also osteoclasts and if this is the case whether they were responsive to calcitonin; to carry out cytogenetic studies on two members of the same family affected by cherubism in an attempt to identify any major chromosomal defects; and to perform an in-depth modern biochemical study of four children in the same family. SUBJECTS AND methods: Four related children with cherubism were studied. Tissue taken from one of the children at elective decompression of an optic nerve was submitted to in vitro bone resorption studies. Cytogenetic studies were done on two of the children and biochemical studies on all four. RESULTS: The multinucleate cells in the cherubic lesions were shown to be osteoclasts since they synthesised tartrate resistant acid phosphatase, expressed the vitronectin receptor, and resorbed bone. bone resorption by the cultured multinucleate cells was significantly inhibited by calcitonin. High resolution cytogenetic studies failed to detect any chromosomal abnormalities in two children with cherubism. The biochemistry profile of all four children with cherubism showed that serum calcium, parathyroid hormone, parathyroid related hormone, calcitonin, and alkaline phosphatase were within normal levels. urine analysis of pyridinium and deoxypyridinium cross links, hydroxyproline, and calcium in relation to urine creatinine were measured to assess bone resorption in these children, and the values were at the upper end of the normal range in all four. CONCLUSIONS: Further studies are required to determine whether calcitonin treatment will control this grossly deforming disease until the time when the physiological changes that occur at puberty rectify the pathology. It is not recommended that biochemical markers of bone resorption are used in isolation to monitor the activity of cherubism in individuals because the results are based on a small number of children and because of reports of marked interindividual variation in the levels of these markers, particularly in children.
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2/21. Osteoclast differentiation and bone resorption in multicentric reticulohistiocytosis.

    Multicentric reticulohistiocytosis (MR) is a systemic disease of unknown cause characterized by the presence of a heavy macrophage infiltrate in skin and synovial tissues and the development of an erosive polyarthritis. The synovial fluid in MR is known to contain numerous mononuclear cells. In this study, we have determined whether these cells contribute to joint destruction in MR by differentiating them into osteoclasts. synovial fluid mononuclear cells were isolated from the knee joint of a 44-year-old male with MR. These cells were cultured with various combinations of macrophage-colony stimulating factor, receptor activator for nuclear factor kappaB ligand (RANKL), tumor necrosis factor alpha, interleukin-1alpha, osteoprotegerin, and zoledronate. Osteoclast differentiation was assessed by expression of tartrate-resistant acid phosphatase, vitronectin receptor, and the extent of lacunar resorption. Most MR synovial fluid mononuclear cells expressed a macrophage phenotype (CD14( ), CD68( ), HLA-DR( ), CD11b( )). Extensive osteoclast formation and lacunar resorption were noted in macrophage-colony stimulating factor/RANKL-treated cell cultures. MR synovial fluid contained increased tumor necrosis factor alpha and decreased osteoprotegerin compared with osteoarthritis synovial fluid. Lacunar resorption was inhibited in cultures containing zoledronate. Pamidronate treatment of the patient also reduced the number of synovial fluid macrophages and resulted in less osteoclast formation and lacunar resorption. MR synovial fluid contains numerous macrophages that are capable of differentiating into osteoclasts by the RANKL signaling pathway. Inhibitors of osteoclast formation and resorption activity may be of use in preventing the severe joint destruction that commonly occurs in MR.
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3/21. in vitro bone resorption by isolated multinucleated giant cells from giant cell tumour of bone: light and electron microscopic study.

    The behaviour of multinucleated giant cells (GCs), obtained from a giant cell tumour of the tibia and cultured on glass coverslips or on devitalized bone slices, was studied using light and electron microscopy. Monitoring the GCs on bone slices by phase-contrast microscopy revealed that they had removed calcified bone matrix resulting in excavation of lacunae, with subsequent lateral extension and perforation of the bone slices. Electron microscopy demonstrated for the first time that the GCs responsible for exavating lacunae had two specific membrane modifications, ruffled border and clear zone, and showed basically similar cytoplasmic fine structures to those of osteoclasts. fluorescence images of the GCs on glass and on bone after rhodamine-conjugated phalloidin staining revealed that most of the GCs had an intensely fluorescent peripheral band composed of a number of F-actin dots called podosomes. Some GCs showed unusual arrangements of podosomes suggesting abortive attempts at GC formation. We have demonstrated that the band structure of the GCs cultured on bone is intimately involved in bone resorption. Two stromal cell types could be recognized. The predominant type, which seemed to be the only neoplastic element because of its proliferative capability, showed quite different fine structural and cytoskeletal features from the GCs. The other type, which was much less frequent and seemed not to proliferate, had morphological similarities to the GCs, and seemed to be their precursor. Importantly GCs cultured on bone and the osteoclasts share common structures for adhesion to and resorption of bone, strongly supporting the view that the GCs of the giant cell tumour of bone are potentially active bone resorbers and can be regarded as osteoclasts.
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4/21. Acne fulminans with osteolytic lesions.

    Multifocal lytic bone lesions were found in a patient with a severe form of acne. The clinical presentation was suggestive of "acne fulminans." propionibacterium acnes was isolated from a subculture of bone tissue. The association of acne fulminans and osteolytic lesions is rare and the pathophysiology is unknown. However, the use of corticosteroids for systemic effect combined with local measures seems to give excellent treatment results.
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5/21. Bone lesions in chronic granulocytic leukaemia.

    Radiographic abnormalities in bone are unusual during the stable phase of chronic granulocytic leukaemia (CGL). A rare situation is reported in which a patient developed three distinctive skeletal lesions simultaneously in different anatomical sites. Firstly, in both fibulae symmetrical punched out and permeative lesions were present throughout much of the shafts, being most prominent in the mid-diaphyseal regions. Secondly, the tibiae were slightly porotic and showed localized periosteal reactions, whereas in the fibulae there was extensive cloaking by a similar but much more intensive reaction. Thirdly, multiple osteosclerotic lesions were present in the pubic bones and in the proximal ends of the femora and humeri. Concurrently, fluctuant, culture negative swellings were present on the extremities. Histological examination of the material from the subcutaneous and lytic lesions showed only areas of fibrosis with islands of haematopoietic tissue, including scanty megakaryocytes. Bone marrow trephine biopsy showed the presence of myelofibrosis with islands of haematopoietic tissue typical of CGL without any evidence of blastic transformation.
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6/21. B cell malignancies presenting with unusual bone involvement and mimicking multiple myeloma. Study of nine cases.

    Nine unusual cases of B cell malignancies presenting with lytic bone lesions on radiography and/or hypercalcemia, and mimicking multiple myeloma are reported in this study. These cases included acute lymphoblastic leukemia (one patient), non-Hodgkin's lymphoma (five patients), chronic lymphocytic leukemia (two patients), and Waldenstrom's disease (one patient). Quantitative bone biopsy performed in two patients (one with non-Hodgkin's lymphoma and one with Waldenstrom's disease) demonstrated a dramatic increase in osteoclastic resorption close to tumor cells in both cases, similar to or even more marked than that observed in multiple myeloma. Finally, significant production of bone resorbing activity was found in short-term liquid culture specimens of tumor cells in eight of the nine cases. These observations clearly indicate that in B cell disorders other than multiple myeloma, the malignant B cells can produce significant bone resorbing activity in vitro and result in excessive osteoclastic resorption and lytic bone lesions, frequent hypercalcemia, and an overall disease picture clinically mimicking multiple myeloma.
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7/21. Production of lymphotoxin, a bone-resorbing cytokine, by cultured human myeloma cells.

    Myeloma cells destroy bone by producing an osteoclast-stimulating factor that has chemical and biological characteristics similar to the bone-resorbing activity present in the supernatants of activated leukocyte cultures. Recently, a number of bone-resorbing leukocyte cytokines have been identified, including interleukin-1, lymphotoxin, and tumor necrosis factor. We have examined the products of human myeloma cells for the presence of these bone-resorbing cytokines. In a tumor cell line derived from a patient who had myeloma with osteolytic bone lesions and hypercalcemia, we found that the myeloma cells induced bone-resorbing activity and cytotoxic activity in vitro. Most of the bone-resorbing activity and all cytotoxic activity were suppressed by neutralizing antibodies to lymphotoxin. The myeloma cells expressed both lymphotoxin and tumor necrosis factor mRNA, but no tumor necrosis factor could be detected in the cell-culture medium. Interleukin-1 mRNA was not detected in the myeloma cells, and biologic activity of interleukin-1 was not measurable in the medium harvested from the cultured cells. The bone-resorbing activity induced by recombinant tumor necrosis factor and recombinant interleukin-1 was not affected by treatment with the lymphotoxin antibodies. When lymphotoxin was infused subcutaneously into normal mice (10 micrograms per day for three days), their plasma calcium levels increased. We also evaluated four established cell lines derived from three other patients with myeloma, and found a similar pattern of lymphotoxin expression in each. It appears that production of the bone-resorbing cytokine lymphotoxin is related to osteoclastic bone destruction and hypercalcemia in patients with myeloma.
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8/21. Nonsecretory multiple myeloma with osteoporosis: immunocytologic and bone resorptive studies.

    Two patients, ultimately found to have advanced nonsecretory multiple myeloma, presented with skeletal pain, diffuse skeletal demineralization, and fractures. The correct diagnosis was initially obscured by the absence of typical hematologic findings and discrete lytic bone lesions. bone marrow examination was diagnostic. Intracytoplasmic IgA or IgD kappa was demonstrated in the myeloma cells of each case. Decreased quantitative polyclonal serum immunoglobulins and hypercalcemia were important clinical clues. The demonstration of increased osteoclast activating factor (OAF) derived from the cultured myeloma cells from each case suggests that the secretion of OAF and immunoglobulin are unrelated.
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9/21. hypercalcemia in chronic myelogenous leukemia: evidence for excessive parathyroid hormone secretion.

    hypercalcemia was associated with osteolytic bone lesions in a 60-year-old woman with chronic myelogenous leukemia in the accelerated phase. Using highly specific antisera to parathyroid hormone, radioimmunoassays disclosed elevated levels of carboxyl-terminal (53-84) and intermediate (44-68) fragments. In addition, concomitant variations of serum calcium level and leukocyte counts, increased urinary c-AMP excretion, morphological integrity of parathyroid glands, and absence of bone resorbing activity in myeloblast culture supernatants are consistent with the hypothesis that the humoral hypercalcemia was due to the excessive production of PTH. This production may have been ectopic, although no PTH secretion was demonstrated in myeloblast culture supernatants.
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10/21. Evidence of bone resorption-stimulating factor in adult T-cell leukemia.

    adult T-cell leukemia (ATL) is known to be frequently accompanied by hypercalcemia, but the mechanisms responsible for hypercalcemia in this disorder are not fully understood. We have recently experienced two male patients (25 and 36 yr old) with ATL diagnosed from typical leukemic cells with grooved and folded nucleus, surface marker, anti-ATLA antibody etc. serum calcium levels of these patients were 16.4 and 21.4 mg/dl, respectively, with no radiological evidence of bone destruction. Peripheral blood leukemic lymphocytes from these patients were purified by the ficoll-Hypaque method and cultured at a concentration of 1.5 X 10(6) cells/ml for 3 days on F-10 medium supplemented with 10% fetal calf serum. The supernatant fluids from the cell cultures were bioassayed for bone resorption-stimulating activity (BRSA) by an assay based on the release of 45Ca from prelabeled fetal mouse forearm bones in organ culture according to Raisz's method. The supernatant fluid of cultures from both patients which showed marked BRSA was nondialyzable through a dialysis membrane with a molecular weight cutoff of 3500. parathyroid hormone and prostaglandins were not detectable in the supernatant fluids of the leukemic cell cultures. In one patient, BRSA was measured twice and found to be decreased to a normal level when the patient was in hematological remission with a normal calcium level (8.3 mg/dl). These results suggest that the hypercalcemia observed in patients with ATL is due, in part, to a bone resorption-stimulating factor which is produced by leukemic T-cell lymphocytes.
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