Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acute effects of salmon calcitonin (SCT) were tested by an SCT induced hypocalcemia test (SCT delta Ca test) in 70 cases of multiple myeloma (MM) (including 52 untreated patients) with bone involvement. Response to SCT in terms of maximum induced hypocalcemia (M delta Ca) was compared to normal controls (NC) and correlated with the main presenting features and clinical status. Acute effects are significantly more marked in MM than in NC (p less than .001). There is a good correlation with the extent of lytic bone lesions (p less than .01), the presence of hypercalcemia (p less than .02) and the myeloma cell mass (p less than .05). After correction for bone involvement response to SCT (M delta Ca) was stronger in IgA lambda MM than in IgG kappa (p less than .01). It is of particular interest that acute effects are significantly more marked in cases of active disease than in non-active disease. We conclude that the SCT delta Ca test might be of practical value in the management of MM.
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PMID:Clinical evaluation of myeloma osteoclastic bone lesions: II. Induced hypocalcemia test using salmon calcitonin. 712 Dec 53

Clodronate (clodronic acid, dichloromethylene bisphosphonate) is a bisphosphonate which has demonstrated efficacy in patients with a variety of diseases of enhanced bone resorption including Paget's disease, hypercalcaemia of malignancy and osteolytic bone metastases. In addition, early reports demonstrating potential efficacy of clodronate in the treatment of osteoporosis suggest a possible role in this debilitating disease. Short term intravenous administration (usually 300 mg/day for 5 days) or longer courses of oral clodronate (usually 1600 mg/day for 6 months) effectively reduced bone pain and/or improved mobility in most patients with Paget's disease, and these effects persisted for up to 12 months after discontinuing clodronate. When administered intravenously (300 mg/day for up to 12 days) to patients with malignant hypercalcaemia, serum calcium levels declined significantly within 2 days of starting treatment and approximately 70 to 95% of patients became normocalcaemic. While there is less experience with oral administration, clodronate (800 to 3200 mg/day) achieved normocalcaemia in the majority of patients, usually within 1 week, and serum calcium levels remained significantly reduced from baseline for up to 6 months with continued treatment. Clodronate is clearly superior to placebo and, based on a retrospective analysis, appears to produce greater and more sustained reductions in serum calcium levels than calcitonin in patients with malignant hypercalcaemia. The few available prospective comparative trials showed that clodronate is at least as effective as etidronate, but comparisons with alendronate and pamidronate produced results of questionable clinical relevance because of low bisphosphonate dosages used in these trials. Nevertheless, single intravenous doses of clodronate 600 mg or alendronate 7.5 mg (both agents repeated on day 3 if necessary) were comparable in efficacy, whereas a single intravenous dose of pamidronate 30 mg was more effective than a single intravenous dose of clodronate 600 mg. Normocalcaemic patients with osteolytic bone metastases due to advanced breast cancer experienced significant reductions in the number of episodes of hypercalcaemia and terminal hypercalcaemia, incidence of vertebral fractures and overall rate of morbid events, including the need for radiotherapy to treat bone-related pain, following treatment with clodronate 1600 mg/day for 3 years in a large placebo-controlled study. A similar large placebo-controlled trial in patients with multiple myeloma demonstrated that clodronate 2400 mg/day orally for 2 years significantly reduced progression of osteolytic bone lesions. Follow-up data from clinical trials revealed that the effects on development of fractures and hypercalcaemia persisted for at least 12 months after the drug was discontinued.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Clodronate. A review of its pharmacological properties and therapeutic efficacy in resorptive bone disease. 752 33

Osteolysis resulting in extensive bone damage is a major clinical manifestation of patients with multiple myeloma (MM). The mechanisms of bone resorption in MM are incompletely understood. The final pathway is the generation of activated osteoclasts within bone marrow (BM) microenvironment. To investigate the mechanisms of bone resorption in MM we established an experimental system that, including bone marrow (BM) stromal cells and bone slices, closely mimicks in vitro the in vivo BM microenvironment. Peripheral blood mononuclear cells (PBMC) from nine patients with MM, three monoclonal gammopathy of undetermined significance (MGUS), and nine normal controls were cultured in this system. PBMC from patients with aggressive and bone devastating MM gave rise to multi-nucleated cells with the morphology and phenotype of osteoclasts. These cells induced bone resorption in vitro which was inhibited by the addition of calcitonin. No bone resorption was observed in cultures of PBMC from patients with MM and limited bone damage, with MGUS and from normal subjects. These findings indicate that patients with aggressive MM have a population of circulating precursors that develop into functionally active osteoclast-like cells once they come in contact with the BM microenvironment. These cells may contribute to the wide-spread and generalized bone erosion observed in the patients.
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PMID:Osteoclast precursors circulate in the peripheral blood of patients with aggressive multiple myeloma. 764 30

In the text are summarized the results of studies dealing with supportive therapy of multiple myeloma bone disease. The similarities of primary osteoporosis and osteoporosis in multiple myeloma raised a hope that sodium fluoride will help to prevent or to slow down the osteoporotic process in multiple myeloma patients. The first studies in small groups of patients reported some advantage for the patients with sodium fluoride, later in randomized studies no benefit of sodium fluoride was confirmed. The effect of calcitonin was studied in small groups of patients. All studies confirmed analgetic effect and some of them proved positive effect on the amount of bone hydroxyapatite by a histomorphometric examination. The contribution of bisphosphonate to the therapy of myeloma patients was confirmed in extensive studies. With the exception of a Canadian study with ethidronate, all studies reported good analgetic effects and the inhibitory influence on bone destruction. The advantage of bisphosphonates in comparison to calcitonin is the possibility of p.o. administration or in i.v. periodical administration several times a year.
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PMID:[Bone manifestations of multiple myeloma and therapeutic possibilities]. 770 7

It has been reported that soluble interleukin (IL)-6 receptor (sIL-6R) is detected in the serum of healthy individuals and its level is increased in patients with multiple myeloma and human immunodeficiency virus infection. Although several reports have suggested that sIL-6R potentiates IL-6 action, its physiological role remains unclear. In this study, we examined the role of sIL-6R on osteoclast formation by IL-6, using a coculture of mouse osteoblasts and bone marrow cells. Neither recombinant mouse IL-6 (mIL-6) nor mouse sIL-6R (smIL-6R) induced osteoclast-like multinucleated cell (MNC) formation when they were added separately. In contrast, simultaneous treatment with mIL-6 and smIL-6R strikingly induced MNC formation. These MNCs satisfied major criteria of authentic osteoclasts, such as tartrate-resistant acid phosphatase (TRAP) activity, calcitonin receptors, and pit formation on dentine slices. The MNC formation induced by mIL-6 and smIL-6R was dose-dependently inhibited by adding monoclonal anti-mouse IL-6R antibody (MR16-1). It is likely that osteoblasts and osteoclast progenitors are capable of transducing a signal from a complex of IL-6 and sIL-6R through gp130, even though they may have no or a very small number of IL-6Rs. Factors such as IL-11, oncostatin M, and leukemia inhibitory factor, which are known to exert their functions through gp130 (the signal-transducing chain of IL-6R), also induced MNC formation in our coculture system. These results suggest that increased circulating or locally produced sIL-6R induces osteoclast formation in the presence of IL-6 mediated by a mechanism involving gp130. This may play an important physiological or pathological role in conditions associated with increased osteoclastic bone resorption.
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PMID:Soluble interleukin-6 receptor triggers osteoclast formation by interleukin 6. 826 49

Bone is lost with advancing age in men as in women, leading to an increased incidence of osteoporotic fractures of the fore-arm, vertebral body and femoral neck. By the ninth decade of life, 4% of men will have sustained a fore-arm fracture, 7% a vertebral fracture and 5% a femoral neck fracture. The absolute number of osteoporotic fractures is rising in men, because of the ageing population and an increase in the age-specific incidence of fractures. Even if the age-specific incidence of fractures stabilizes, demographic trends suggest that a further increase in the number of men with osteoporotic fractures is inevitable. Peak bone mass in men is influenced by race, hereditary, hormonal factors, physical activity and calcium intake during childhood and adolescence. Bone loss in men starts at about the age of 35 years and is regulated by genetic, endocrine, mechanical and nutritional factors. Secondary causes of osteoporosis may be detected in about 55% of men with vertebral crush fractures. The major causes are steroid therapy, hypogonadism, skeletal metastases, multiple myeloma, gastric surgery and anticonvulsant treatment. Hypogonadism is found in up to 20% of men with vertebral crush fractures, although the clinical features of testosterone deficiency may not always be present. Hypogonadal osteoporosis is associated with increased bone resorption and decreased mineralization, which is reversed by treatment with testosterone, leading to an increase in bone density. There is little published information on the treatment of primary osteoporosis in men. Although calcitonin, bisphosphonates and testosterone may be effective in the management of osteoporosis in men, confirmation is required in formal clinical trials.
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PMID:Osteoporosis in men. 829 92

The aim of the study was to evaluate the efficacy of half-year treatment of bone mineral disturbances with calcitonin in the patients with multiple myeloma. Thirty five patients (11 men and 24 women) were examined. They were treated among other with prednisone. Nineteen patients (15 patients with normal bone mineral density of lumbar spine and femoral neck and 4 with low bone mineral density who could not be treated with calcitonin) were treated only with chemotherapy. Other 16 patients with low bone mineral density have received also calcitonin (100 units subcutaneous daily) with vitamin D3 and calcium carbonate. Bone mineral density was evaluated with dual energy X-ray absorptiometry in lumbar spine and femoral neck. After treatment with calcitonin there was more pronounced influence on bone mineral density in lumbar spine and femoral neck than after treatment with chemotherapy only but the difference was not statistically significant. Because the bone mineral disturbances in the patients with multiple myeloma is the big problem there is a need for further and longer evaluation of the treatment of these disturbances.
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PMID:[Effect of calcitonin treatment on bone mineralization in patients with multiple myeloma]. 864 23

Interleukin-6 (IL-6) is known to enhance osteoclast recruitment, and thereby bone resorption. Thus, IL-6 has been proposed to mediate hypercalcemia in multiple myeloma and the enhanced osteoclastic activity seen in postmenopausal osteoporosis. We recently reported that the calcium concentration in plasma affects IL-6 secretion from mononuclear blood cells. To investigate the underlying mechanism, we have studied the effect of calcium on IL-6 formation in mononuclear blood cells ex vivo and in vitro. Thirteen healthy volunteers were given 1 g of calcium orally after overnight fasting. Plasma levels of ionized calcium (pCa2+) and serum levels of parathyroid hormone (sPTH) were measured after 2 and 4 h, with all subjects still fasting. After 2 h, pCa2+ was increased and sPTH decreased in all 13 persons. IL-6 secretion ex vivo from mononuclear blood cells drawn 4 h after calcium intake was increased 185% as compared with IL-6 secretion from cells drawn just before calcium intake. In control experiments without calcium intake, there was no alteration in pCa2+ and no effect on IL-6 secretion from mononuclear blood cells. In vitro studies revealed that stimulation of isolated mononuclear blood cells with physiological concentrations of calcium dose-dependently increased IL-6 secretion with an estimated EC50 at 1.2 mM Ca2+. No effect on the IL-6 secretion was seen following treatment of the isolated mononuclear blood cells with PTH or calcitonin. These observations demonstrate that the plasma calcium concentration affects IL-6 secretion from mononuclear blood cells. The in vitro data indicate the involvement of a direct calcium sensing mechanism. These findings might have implications in hypercalcemia and should also be borne in mind when considering the role of cytokines in osteoporosis.
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PMID:Regulation of interleukin-6 secretion from mononuclear blood cells by extracellular calcium. 904 Oct 54

Gallium nitrate was originally developed as an antineoplastic agent; however, further studies have revealed that this drug has extremely potent effects on turnover of bone, and that low doses can be used to reduce bone resorption. Like the bisphosphonates, gallium nitrate has been studied in both malignant and in nonmalignant conditions. The results of randomized double blind studies have suggested that this drug has superior clinical efficacy relative to etidronate, calcitonin, and pamidronate for the acute control of cancer-related hypercalcemia. In patients with Paget's disease, low doses of gallium nitrate reduce biochemical parameters of accelerated bone turnover, including urinary excretion of calcium, hydroxyproline, and urinary collagen cross-linked N-telopeptides. Preliminary studies showed similar effects in patients with bone involvement from a wide variety of tumor types. Based on this high degree of clinical potency revealed in clinical studies, two randomized Phase III studies have been initiated in patients with bone metastases from breast carcinoma and bone involvement due to multiple myeloma. Both studies employ cyclic therapy with low dose gallium nitrate (i.e., 40 mg administered as a subcutaneous injection once daily for 2 weeks, followed by 2 weeks off treatment, recycled monthly). The endpoints of both studies are to document reductions in time to "morbid skeletal events," such as palliative skeletal radiotherapy, stabilizing orthopedic surgery, or pathologic fractures, as well as decreases in pain and analgesic requirements and improvements in mobility and other aspects of quality of life. These trials should provide definitive evidence of whether this agent is safe and effective as a treatment for bone metastases.
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PMID:Gallium nitrate for the treatment of bone metastases. 936 36

A 72-year-old patient with multiple myeloma was admitted to the intensive care unit because of hypercalcemic crisis and acute renal failure. After 7 days of comprehensive therapy including diuretics steroids, calcitonin, and intermittent hemodialysis (IHD) with low-calcium dialysate, calcium still reached high levels between IHD treatments and thrombocytopenia developed after chemotherapy. CVVHDF with calcium-free bicarbonate dialysate was started. Anticoagulation with 2.2% citrate was performed in order to chelate calcium, and thus treat the hypercalcemia, and to provide regional anticoagulation, and thus reduce the risk of bleeding due to thrombocytopenia. CVVHDF with citrate anticoagulation was continued for 6 days, and standard heparin anticoagulation was started when the hypercalcemia and thrombocytopenia abated.
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PMID:Continuous venovenous hemodiafiltration (CVVHDF) with citrate anticoagulation in the treatment of a patient with acute renal failure, hypercalcemia, and thrombocytopenia. 956 11


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