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)

The search into the way in which skeletal metastases develops has not only shown that there are several mechanisms for the progressive bone destruction and bone formation that occur simultaneously in the majority of skeletal metastases, but also that an understanding of these basic mechanisms has significant therapeutic implications. Our results have shown that there are two main mechanisms for the bone formation: stromal bone formation and reactive bone formation. The former occurs in tumours which tend to be acellular, with a large fibrous stroma, whereas the latter occurs in virtually all metastases. There is no difference in the basic pathological process of sclerotic or lytic metastases, the radiographic appearance purely indicating the net balance between the different types of bone formation and the simultaneous progressive bone destruction. An understanding of the pathophysiological response to skeletal metastases explains why skeletal scintigraphy can be used to diagnose these lesions and the different mechanisms underlying the 'three-phase scintigram'. The first phase indicates the vascularity of the lesion; the second phase or 'blood-pool' image indicates the concentration in the extracellular fluid and the third phase or 'skeletal or delayed image' indicates the uptake in the reactive new bone. The secretion of an osteoblast inhibiting factor by myeloma indicates why there is no reactive bone produced by the majority of lesions in the absence of a fracture, and why scintigraphy is less reliable than plain radiographs for the detection of the lesions. There are two main mechanisms for the bone destruction, the most important being mediated via osteoclasts. An understanding of the humoral mechanisms stimulating the osteoclast proliferation may lead to more effective treatment of malignant hypercalcaemia and lytic metastases. Early results of use of APD are encouraging, and our results also suggest that clinical trials should be established to evaluate the effect of combination therapy with APD or prostaglandin inhibitor combined with the agents normally used in the management of patients with disseminated mammary carcinoma. The development of treatments to inhibit tumour-induced osteolysis will minimise the complications of pathological fracture, spinal instability, etc., and even if these treatments do not affect the primary tumour, its ability to metastasize, or the patient's survival, such treatment will be a major advance in the management of patients with carcinoma, because of the significant morbidity currently associated with the development of skeletal metastases and their complications.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The development of skeletal metastases. 279 40

The effects of the treatment of multiple myeloma (MM) with APD-bisphosphonate on bone destruction, the dissemination pattern of the MM, and toxicity for normal and malignant cells were investigated in an animal model, the 5T2 MM. This mouse MM very closely resembles the human disease, including the typical bone lesions. It was demonstrated by radiography, microradiography, and histologic investigation that the treatment of the 5T2 MM with APD-bisphosphonate protected the mice against a loss of bone to a significant extent. It seemed that the treatment with APD not only diminished the bone destruction by the MM but also led to the formation of new bone in already-affected bone tissue. The growth pattern of the MM was not substantially influenced by the treatment, even though there was an indication that APD exerts some cytotoxic effect on the MM cells.
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PMID:Influence of treatment with APD-bisphosphonate on the bone lesions in the mouse 5T2 multiple myeloma. 396 88

For 2 weeks 27 patients with hypercalcemia received a standard oral treatment with (3-amino-1-hydroxypropylidene)-1,1-bisphosphonate (APD) as the sole agent. Results were grouped according to causes of hypercalcemia and compared with effects of APD in 13 normocalcemic patients with Paget's disease of bone and 7 with osteoporosis. In 12 hypercalcemic patients with osteolytic bone lesions and in the 20 normocalcemic patients, the mean serum calcium decreased to final levels that were subnormal and significantly lower than those obtained after treatment of 8 patients with primary hyperparathyroidism. In 3 patients with myeloma and in 4 tumor patients without bone lesions, serum calcium did not always decrease to the normal range. Implications of these observations for the mechanism of hypercalcemia are discussed.
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PMID:Efficacy of amino-hydroxypropylidene bisphosphonate in hypercalcemia: observations on regulation of serum calcium. 681 19

Frequent complications of bone metastases include pain, pathologic fracture, hypercalcemia and spinal cord compression. Lytic bone metastases result from excessive activation of osteoclasts by tumor-produced cytokines. Aredia (pamidronate) is a potent bisphosphonate that inhibits osteoclast activation. In two dose-seeking phase I trials in patients with breast cancer and prostate cancer, repeated intravenous infusion of Aredia was shown to be safe and effective in reducing bone resorption and pain. In a randomized phase III trial of 377 patients with multiple myeloma, Aredia was administered in a dosage of 90 mg i.v. every 4 weeks. Compared with placebo, treatment with Aredia was associated with a significant decrease in bone pain and in the incidence and time to development of all skeleton-related events. Data from two phase III breast cancer trials each involving 300 patients are now being analyzed. The newer bisphosphonates can safely be used together with standard anticancer therapy to provide effective palliation of symptoms caused by lytic bone metastases.
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PMID:The role of bisphosphonates in the treatment of bone metastases--the U.S. experience. 873 55

Pamidronate (APD) is a potent inhibitor of bone resorption that is useful in the management of patients with osteolytic bone metastases from breast cancer or multiple myeloma, tumour-induced hypercalcaemia or Paget's disease of bone. After intravenous administration, the drug is extensively taken up in bone, where it binds with hydroxyapatite crystals in the bone matrix. Matrix-bound pamidronate inhibits osteoclast activity by a variety of mechanisms, the most important of which appears to be prevention of the attachment of osteoclast precursor cells to bone. In patients with osteolytic bone metastases associated with either breast cancer or multiple myeloma, administration of pamidronate together with systemic antitumour therapy reduces and delays skeletal events, including pathological fracture, hypercalcaemia and the requirement for radiation treatment or surgery to bone. Pamidronate generally improves pain control. Quality-of-life and performance status scores in pamidronate recipients were generally as good as, or better than, those in patients who did not receive the drug. Overall survival does not appear to be affected by pamidronate therapy. Tumour-induced hypercalcaemia also responds well to pamidronate therapy: 70 to 100% of patients achieve normocalcaemia, generally 3 to 5 days after treatment. Response durations vary, but are commonly 3 weeks or longer, In comparative studies, pamidronate produced higher rates of normocalcaemia and longer normocalcaemic durations than other available osteoclast inhibitors, including intravenous etidronate, clodronate and plicamycin (mithramycin). In most patients with Paget's disease of bone, intravenous pamidronate reduces bone pain and produces biochemical response. Serum alkaline phosphatase levels generally fall 50 to 70% from baseline 3 to 4 months after pamidronate treatment. Biochemical response may be prolonged. Pamidronate is well tolerated by most patients. Transient febrile reactions, sometimes accompanied by myalgias and lymphopenia, occur commonly after the first infusion of pamidronate. Other reported adverse events include transient neutropenia, mild thrombophlebitis, asymptomatic hypocalcaemia and, rarely, ocular complications (uveitis and scleritis). Pamidronate should be considered for routine use together with systemic hormonal or cytotoxic therapy in patients with breast cancer or multiple myeloma and osteolytic metastases. At present, pamidronate is the drug of choice for first-line use in the management of patients with tumour-induced hypercalcaemia. It is an effective treatment for Paget's disease and is the treatment of choice where oral bisphosphonates are not an option.
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PMID:Pamidronate. A review of its use in the management of osteolytic bone metastases, tumour-induced hypercalcaemia and Paget's disease of bone. 950 93

Bone is one of the most frequent organs to be affected by metastatic cancer and causes more morbidity than any other metastatic site. Bisphosphonate treatment provides an organ-specific treatment which is relevant to most if not all tumour types involving bone. Bisphosphonates, particularly the potent agent pamidronate (Aredia), will relieve metastatic bone pain with a consequent improvement in quality of life in approximately 50% of patients. Long-term bisphosphonate treatment clearly reduces skeletal morbidity rates in multiple myeloma and breast cancer.
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PMID:How can we improve the treatment of bone metastases further? 980 53

Metastatic bone disease develops as a result of the many interactions between tumour cells and bone cells. This leads to disruption of normal bone metabolism, with the increased osteoclast activity seen in most, if not all, tumor types providing a rational target for treatment. The clinical course of metastatic bone disease in multiple myeloma, breast and prostate cancers is relatively long, with patients experiencing sequential skeletal complications over a period of several years. These include bone pain, fractures, hypercalcaemia, and spinal cord compression, all of which may profoundly impair a patient's quality of life. External beam radiotherapy and systemic endocrine and cytotoxic treatments are the mainstay of treatment in advanced cancers. However, it is now clear that the bisphosphonates provide an additional treatment strategy, which reduces both the symptoms and complications of bone involvement. Pamidronate (Aredia(TM)) is the most widely evaluated bisphosphonate and is recommended for most patients with multiple myeloma or breast cancer with bone metastases. Current research aims include the evaluation of new potent bisphosphonates such as zoledronic acid (Zometa(TM)). It is hoped that this compound is not only more convenient and easier to administer but also more effective in inhibiting skeletal morbidity. Zometa may also have some direct anticancer activity. Preclinical studies with Zometa have demonstrated its potential in malignant bone disease. Clinical studies in treatment of hypercalcemia of malignancy have been completed, as have Phase I and II trials in patients with cancer and pre-existing bone metastases. Three randomized, double-blind, controlled Phase III trials are now ongoing to establish the efficacy and safety of Zometa in treatment of bone metastases in patients with osteolytic and osteoblastic lesions. Additionally, new specific molecules such as osteoprotogerin have been developed that are based on our improved understanding of the cellular signalling mechanisms involved in cancer induced bone disease. These potent molecules are now entering clinical trials. Ongoing research is aimed at trying to define the optimum route, dose, schedule and type of bisphosphonate in metastatic bone disease and their use in the prevention and treatment of osteoporosis in cancer patients. In vitro suggestions of direct anti-cancer activity and some promising clinical data in early breast cancer have resulted in considerable interest in the possible adjuvant use of bisphosphonates to inhibit the development of bone metastases.
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PMID:Optimising treatment of bone metastases by Aredia(TM) and Zometa(TM). 1111 66

Collapsing focal segmental glomerulosclerosis (FSGS) is a distinct clinicopathologic entity seen most commonly in young African American patients who present with renal insufficiency and nephrotic syndrome. The only epidemiologic factor previously linked to collapsing FSGS is HIV infection. Here clinicopathologic findings are reported for a distinctive population of seven patients, who were older, Caucasian, and HIV negative and developed collapsing FSGS during active treatment of malignancy (multiple myeloma in six patients and metastatic breast carcinoma in one). Although oncologic treatment regimens included vincristine for four patients, doxorubicin for five patients, cisplatin for two patients, and total-body irradiation for one patient, the only agent common to all patients was pamidronate (Aredia). All patients had normal renal function before the administration of pamidronate. Patients began therapy with pamidronate at or below the recommended dose of 90 mg, intravenously, monthly, which was increased to 180 mg monthly in two patients and 360 mg monthly in three patients. Patients received pamidronate for 15 to 48 mo before presentation with renal insufficiency (mean serum creatinine, 3.6 mg/dl) and full nephrotic syndrome (mean 24-h urinary protein excretion, 12.4 g/d). Pamidronate, which is a member of the class of bisphosphonates, is widely used in the treatment of hypercalcemia of malignancy and osteolytic metastases. At the recommended dose of 90 mg, intravenously, monthly, renal toxicity is infrequent; however, higher doses have produced nephrotoxicity in animal models. The temporal association between pamidronate therapy and the development of renal insufficiency, the use of escalating doses that exceed recommended levels, and the distinctive pattern of glomerular and tubular injury strongly suggest a mechanism of drug-associated podocyte and tubular toxicity. These data provide the first association of collapsing FSGS with toxicity to a therapeutic agent.
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PMID:Collapsing focal segmental glomerulosclerosis following treatment with high-dose pamidronate. 1137 39

The knowledge and training of nursing staff is essential for the safety and comfort of patients receiving i.v. therapies. The use of i.v. bisphosphonates as an adjunct to standard antineoplastic therapies in patients with advanced cancer is becoming widespread. Zoledronic acid and pamidronate (Zometa and Aredia, Novartis Pharmaceuticals Corporation, East Hanover, NJ) are nitrogen-containing bisphosphonates. Pamidronate has been the standard of care for patients with osteolytic bone lesions from breast cancer or multiple myeloma. However, zoledronic acid, which has demonstrated increased potency and a broad clinical utility, is emerging as the new standard of care. In addition to treating hypercalcemia of malignancy, zoledronic acid is approved for treating patients with bone metastases (osteolytic or osteoblastic) from a wide range of solid tumors, including breast, prostate, and lung cancers, or osteolytic bone lesions from multiple myeloma. Zoledronic acid (4 mg via a 15-minute infusion) has a safety profile comparable with pamidronate (90 mg via a two-hour infusion) and has demonstrated comparable or superior efficacy to that of pamidronate in every patient population tested. The shorter infusion time of zoledronic acid compared with that of pamidronate may provide added convenience, but safety guidelines should be followed for all i.v. bisphosphonate therapies. These guidelines and nursing care of patients receiving i.v. bisphosphonates are reviewed.
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PMID:Advances in supportive care of patients with cancer and bone metastases: nursing implications of zoledronic acid. 1292 73

Jaw bone necrosis is a clinical condition associated with defects in vascularization of the maxilla or the mandibular bone, usually present following head and neck radiotherapy and/or oral surgical interventions. Bisphosphonates are synthetic analogues of pyrophosphate used in the treatment of patients with hypercalcemia as a result of malignancy, bone metastasis and for the treatment of other disorders such as metabolic bone diseases, Paget's disease and osteoporosis. Over last 10 years, cases of jaw bone necrosis have been associated with the use of bisphosphonate therapy. In particular, Ruggiero et al. (J Oral Maxillofac Surg 2004; 62: 527-534) in 2004 described a large group of patients (63) with jaw bone necrosis probably related to the use of these drugs. It should be noted that all the patients in the group described either underwent head and neck radiotherapy or had a dental extraction while taking bisphosphonates. In the present study, we reported four cases of jawbone necrosis in patients taking pamidronate (Aredia) and zoledronate (Zometa) without having undergone any kind of radiotherapy or dental surgery. All the patients were females between the ages of 56 and 71 years; three were treated with bisphosphonates for bone metastasis and one for multiple myeloma. All the patients received surgical treatment with bone curettage, with partial and/or temporary improvement of the lesions. Although a treatment for bisphosphonate-induced bone lesions has not yet been established, we suggest careful evaluation of the patients' oral health before prescribing bisphosphonate treatment.
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PMID:Jaw bone necrosis without previous dental extractions associated with the use of bisphosphonates (pamidronate and zoledronate): a four-case report. 1620 82


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