Cases reported "Bone Resorption"

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1/27. hypercalcemia induced with the plasma levels of parathyroid hormone-related peptide in multiple myeloma.

    A 69-year-old man visited our department of neurology with symptoms of paresthesia on the lower extremities and lumbago. Biochemical examination of serum samples showed hypercalcemia (serum concentration 15.6 mg/dl). The levels of intact parathyroid hormone (i-PTH) and 1,25-dihydroxyvitamin D were suppressed, whereas parathyroid hormone-related peptide (PTHrP) was elevated up to 5.4 pM (normal range: below 0.6 pM). Additionally, bone survey revealed a punched-out lesion in radiological examinations of the skull. bone marrow aspiration demonstrated many atypical plasma cells suggesting multiple myeloma. Nephrogenous cyclic adenosine monophosphate (cAMP), urinary deoxypyridinoline, plasma interleukin 6 (IL-6) and transforming growth factor beta (TGF beta) concentrations were elevated, whereas % of renal tubular reabsorption of phosphate (%TRP) was decreased. The immunohistochemical results demonstrated the expression of PTHrP in atypical plasma cells. These data indicated that hypercalcemia complicating multiple myeloma causes an elevation of renal calcium reabsorption and an increase of bone resorption mediated by PTHrP action.
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2/27. New insights on the pathogenesis of hypercalcemia in primary hyperparathyroidism.

    The pathogenesis of hypercalcemia in primary hyperparathyroidism is attributed to increased calcium release from bone, increased calcium reabsorption in renal distal tubules, and increased intestinal calcium absorption. However, it remains unclear which factor is the main process. We encountered a 56-year-old woman with myasthenia gravis, in whom hypercalcemia and elevated serum parathyroid hormone (PTH) level were observed. diagnosis of primary hyperparathyroidism was made. Treatment with methylprednisolone for myasthenia gravis was associated with a marked decrease in both biochemical markers of bone formation and resorption without any changes in endogenous cAMP and serum levels of calcium, PTH, and 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]. These findings suggest that the possible pathogenesis of hypercalcemia in primary hyperparathyroidism may be attributed to the increased calcium reabsorption in the kidney and the increased intestinal calcium absorption as a result of stimulated production of 1,25-(OH)2D3 in the kidney. It thus follows that the renal tubular effect rather than the skeletal effect of the PTH excess may play a pivotal role in the development of hypercalcemia in primary hyperparathyroidism.
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3/27. parathyroid hormone-related protein induced coupled increases in bone formation and resorption markers for 7 years in a patient with malignant islet cell tumors.

    parathyroid hormone-related protein (PTHrP) and PTH share the common PTH/PTHrP receptor. Although an elevated level of circulating PTHrP in patients with malignancies causes hypercalcemia as does PTH, chronic and systemic effects of PTHrP on bone metabolism in humans are not well understood because tumor-burden patients showing hypercalcemia usually have a poor prognosis. We investigated bone and calcium metabolism in a patient with malignant islet cell tumors showing hypercalcemia due to the elevated plasma PTHrP level for 7 years. hypercalcemia and hypercalciuria continued throughout the clinical course in spite of frequent infusions of bisphosphonates. bone resorption markers and a bone formation marker were consistently elevated as seen in primary hyperparathyroidism, a disease caused by an autonomous hypersecretion of PTH. Based on biochemical measurements including bone markers and serum 1,25-dihydroxyvitamin D, the clinical features of this case essentially are the same as those of primary hyperparathyroidism except for the elevated level of plasma PTHrP with suppressed intact PTH level. Therefore, it is suggested that chronic and systemic effects of PTHrP on bone as well as calcium metabolism are indistinguishable from those of PTH in human.
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4/27. Cortisol-dihydrotachysterol antagonism in a patient with hypoparathyroidism and adrenal insufficiency: apparent inhibition of bone resorption.

    This report describes a case of chronic mucocutaneous candidiasis with associated hypoparathyroidism and acutely developed adrenocortical insufficiency. The latter was heralded by hypercalcemia. Upon the institution of cortisol therapy, while still under the effects of a vitamin d analog dihydrotachysterol (DHT), the patient exhibited severe hypocalcemia and tetany. Since calcium intake was minimal during this period of presumed corticosteroid-DHT antagonism, it is suggested that the cortisol disturbed calcium homeostasis by in inhibiting bone calcium resorption.
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5/27. Hypercalcaemia in Addison's disease: calciotropic hormone profile and bone histology.

    Three cases of hypercalcaemia secondary to acute adrenocortical insufficiency are described; all the patients had moderate to severe renal impairment, one being on chronic dialysis treatment with no residual diuresis. Parathyroid hormone (PTH) and 1,25 dihydroxyvitamin D [1,25(OH)2D] were low, indicating a suppressed PTH-vitamin d axis. In the two patients with partial renal impairment, urine Ca excretion was increased, indicating increased load of the cation into the extracellular fluid (ECF), most probably from bone. Saline infusion, to correct any ECF depletion and to increase urine Ca excretion, could not fully correct the hypercalcaemia. Complete correction of plasma Ca levels was observed shortly after the institution of hormonal substitutive therapy. Despite the evidence of increased Ca mobilization from bone, bone biopsies in two patients did not show any signs of cell-mediated bone resorption; instead, bone cell activity appeared to be suppressed. Thus, glucocorticoid deficiency appears to induce Ca mobilization from bone stores by mechanism(s) unrelated to bone remodelling processes.
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6/27. The role of 1,25-dihydroxyvitamin D in the maintenance of hypercalcemia in a patient with an ovarian carcinoma producing parathyroid hormone-related protein.

    The syndrome of humoral hypercalcemia of malignancy (HHM) is thought to be mainly a result of the production of parathyroid hormone-related protein (PTHRP) by malignant tumors. serum 1,25-dihydroxyvitamin D (1,25-DHD) concentrations are generally low in such patients, which contrasts with the findings in animal studies. A patient is reported with HHM from a clear cell ovarian carcinoma and elevated serum immunoreactive PTHRP (about five times the upper limit of normal) in whom serum 1,25-DHD concentrations were abnormally high (200 pmol/l) and associated with increased intestinal calcium absorption. Treatment with two different nitrogen-containing bisphosphonates (pamidronate and [3-dimethyl-amino-1-hydroxypropylidene]-1,1-bisphosphonate) did not normalize serum and urinary calcium despite effective inhibition of bone resorption. These observations suggested an additional intestinal contribution to the maintenance of hypercalcemia. Tumor removal was followed by decreases in serum immunoreactive PTHRP and 1,25-DHD concentrations to their respective normal ranges and normocalcemia. Separating HHM into Types I and II, according to the prevailing serum 1,25-DHD concentrations, can provide a basis for a better understanding of the pathogenesis of hypercalcemia, and it also may have practical use in the successful management of these patients.
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7/27. Inhibition of mediator release in systemic mastocytosis is associated with reversal of bone changes.

    A 59-year-old male presented with systemic mastocytosis with extensive skeletal involvement resulting in vertebral compression fractures and bone pain. Histomorphometric analysis of bone revealed increased mast cells, elevated static parameters of bone resorption, and low bone formation. serum calcium, phosphorus, and alkaline phosphatase were normal; however, serum 1,25-dihydroxyvitamin D3 and osteocalcin levels were low. histamine levels in plasma and urine were elevated. Following therapy with ketotifen, the patient had resolution of bone pain along with decreased flushing and pruritus. Elevated plasma and urine histamine levels normalized, as did 1,25-dihydroxyvitamin D3 and osteocalcin levels. Indices of low bone formation improved on therapy. Eroded surfaces improved but remained elevated. This case is the first demonstration that bone symptoms and histomorphometric change in systemic mastocytosis are reversed with inhibition of mast cell degranulation. The role of mast cells and their products in bone metabolism is poorly understood, but the therapy of bone disease in systemic mastocytosis should include inhibition of the release of mast cell products along with the use of histamine antagonist.
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8/27. acromegaly and proximal femoral fracture in an aged person: bone histomorphometry, vitamin d metabolites and parathormone.

    osteoporosis and fractures are rare in acromegaly. An 84-year-old acromegalic woman sustained a fractured neck of femur in a fall. Histomorphometric analysis of an iliac crest biopsy showed marked osteoporosis and augmented resorption parameters. Cortical plates were very thin and bone volume was 8.5%; 12.5% is the reference value for women at this age. The total resorption surfaces were 23.7% compared with the reference value of 8%. We conjecture that postmenopausal and involutional osteoporosis were far advanced before the development of acromegaly, explaining the coexistence of the two conditions. Parathormone (65 pmol/l) and 24,25-dihydroxyvitamin D (1.34 ng/ml) levels were within normal limits, but those of 25-hydroxyvitamin D (5.6 ng/ml) and 1,25-dihydroxyvitamin D (15 pg/ml) were markedly decreased.
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9/27. hypocalcemia associated with estrogen therapy for metastatic adenocarcinoma of the prostate.

    We report 2 cases of true hypocalcemia (not caused by decreased binding proteins) associated with metastatic prostate cancer and review previously reported cases. hypocalcemia is a common but frequently unrecognized complication of prostatic cancer. Estrogen therapy often is associated with the hypocalcemia, which may be asymptomatic. The hypocalcemia is always associated with osteoblastic metastases and usually it is associated with increased serum alkaline phosphatase activity, acid phosphatase activity and serum parathyroid hormone concentration. serum concentrations of magnesium, phosphorus and vitamin d frequently are decreased. patients are in a positive calcium balance. The osteoblastic metastases seem to act as a calcium sink, creating a "hungry tumor phenomenon". The role of estrogens may be to stop the resorption of normal bone resulting in lower serum calcium concentrations.
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10/27. Malignant osteoporosis and defective immunoregulation.

    The linkage between immune cells and the osteoclast has become partially understood in the laboratory, but the full spectrum of clinical disorders of this relationship remain to be elucidated. We report a 29-month-old girl with recurrent infections and multiple fractures. Immune evaluation showed normal quantitative serum immunoglobulins but absent antibodies to the respiratory viruses and tetanus toxoid and decreased in vitro polyclonal-induced immunoglobulin production. Further analysis in vitro with separated lymphocyte populations showed normal B cell function but markedly increased suppressor T cell activity. The bone evaluation showed diffuse osteopenia on x-ray. serum calcium, phosphorus, PTH, 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D were normal for age. Urinary calcium excretion (24 h) was, however, two times normal. An iliac crest biopsy confirmed the presence of extreme osteopenia with normal mineralization and numerous small atypical osteoclasts resorbing the bone. No circulating plasma resorptive activity was demonstrated. calcitonin therapy markedly diminished the patient's hypercalciuria. We speculate that this patient's increased bone resorption, decreased bone formation, and suppressor activity may be linked by a common pathway involving the abnormal function of immune cells. Since no similar constellation of findings has been previously reported, this case may represent a new congenital disorder: severe osteopenia associated with increased osteoclast activity in association with a defect in T cell immunoregulation.
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