Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0005940 (bone disease)
 7,459 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bisphosphonates are nonbiodegradable pyrophosphate analogs that are capable of inhibiting bone resorption in vivo and in vitro. For this reason they have been used as effective therapeutic agents in several conditions characterized by increased bone turnover, including Paget's disease, hypercalcemia of malignancy, and metastatic bone disease. More recently, bisphosphonates have been proposed for the treatment and prevention of bone loss in several forms of osteoporosis. Etidronate, the first bisphosphonate to be used in clinical trials, has been found to increase vertebral bone mineral mass in osteoporotic patients. However, the gain in bone mass reaches a plateau after 1-2 years of treatment, with no further increase thereafter. No positive effect on osteoporotic fracture rate has been clearly demonstrated. Moreover, etidronate has been shown to impair bone formation and mineralization at therapeutic doses. Newer, more potent bisphosphonates selectively inhibit bone resorption without impairing bone histology and mechanical strength. Pamidronate has been shown to increase vertebral bone mass in patients with steroid-induced osteoporosis and involutional osteoporosis. In the latter group, this increase did not plateau and was found to be sustained for at least 4 years. However, pamidronate use is associated with relatively poor gastrointestinal tolerability. The use of another agent, clodronate, has been limited by the possible link with the onset of hematologic malignancies. Alendronate is another agent which in studies to date has been found to increase vertebral bone mass in postmenopausal patients. Alendronate also seems to be more potent and better tolerated than pamidronate.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Clinical trials with bisphosphonates. 129 94

The treatment of hypercalcemia of malignancy is troublesome. Personal experience with breast cancer associated hypercalcemia is presented. Eight patients were hydrated with intravenous administration of saline solution containing high doses of salmon calcitonin and subsequently six were treated with antiblastic polychemotherapy. Calcium level fell to normal in all patients. Hypercalcemia, with or without evidence of metastatic bone disease, may be caused by the production of humoral substance by tumoral tissue. In our experience the first therapeutic stage is the infusion of saline solution containing high doses of calcitonin, while the elective treatment is antiblastic polychemotherapy which, acting on tumour growth, may inhibit the release of humoral mediators of hypercalcemia causing a slower but stable reduction in serum calcium level.
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PMID:[Update on paraneoplastic hypercalcemia. Our experience in the treatment of hypercalcemic states of patients with advanced breast carcinoma]. 340 54

Osteoporosis is the most important metabolic bone disease and places an increasing burden on the healthcare system. The condition can be prevented by the early introduction of hormone replacement therapy. The role of bisphosphonates in achieving the same result is being actively explored. The attraction of preventing bone loss is that it preserves the micro-architecture of bone, and therefore its mechanical integrity. The great problem of treating the established condition is that substantial bone loss is accompanied by architectural disintegration. Replacing lost bone may not necessarily restore mechanical integrity and protect against fractures. The management of Paget's disease has been quite revolutionised by the introduction of the bisphosphonates. The condition is a result of a primary increase in osteoclastic bone resorption which can be corrected by bisphosphonates, with considerable symptomatic improvement. The increasing potency and safety margin of the newer agents has meant that the threshold for treatment has fallen. There is now potential for long term control of bone turnover with the hope of preventing late complications. Hypercalcaemia of malignancy is usually the result of both increased bone destruction and decreased urinary calcium excretion. These two components of hypercalcaemia demand different approaches to management. The general availability of an ever-expanding range of increasingly potent bisphosphonates has resulted in a dramatic improvement in the treatment of increased bone resorption associated with malignancy. Many types of tumour, either directly or indirectly, compromise the ability of the kidney to eliminate a calcium load derived from increased bone destruction. Calcitonin is the only agent which is currently available to counter this process.
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PMID:Drugs used in the treatment of metabolic bone disease. Clinical pharmacology and therapeutic use. 750 48

Bisphosphonates are analogues of inorganic pyrophosphate, a naturally occurring chemical in bone. In vitro and animal experiments demonstrated that these agents were effective inhibitors of bone resorption. Subsequently they were applied to a variety of clinical problems in which increased bone resorption was an underlying feature of the pathology. In 1971 etidronate became the first bisphosphonate shown to inhibit bone resorption in humans when it was given to patients with Paget's disease. Subsequently this agent was also found to be useful in treating the hypercalcemia of malignancy. At the present time cyclic etidronate therapy is also used for the prevention of bone loss in patients with osteoporosis and for the prevention of heterotopic ossification in spinal cord-injured patients and in patients after hip replacement. Newer bisphosphonates are generally more potent than etidronate and do not produce a severe mineralization defect as do higher doses of etidronate. Pamidronate and clodronate are highly effective in the management of Paget's disease, hypercalcemia due to malignancy and immobilization, metastatic bone disease, and hematologic malignancies affecting bone. They are also promising agents for the prevention of osteoporosis. Alendronate, risedronate, and CGP 42446 are highly potent bisphosphonates that look very promising for the treatment of all disorders of bone resorption. It is fortunate that adverse reactions are not a prominent feature of bisphosphonate use. The main side effects are nausea and abdominal discomfort, mainly with oral use, a transient increase in bone pain in patients with Paget's disease, and an acute-phase reaction (fever, myalgia, mild leukopenia) in patients receiving aminobisphosphonates. The evolution of bisphosphonate therapy should be considered one of the major therapeutic events of the past 25 years. Future research should define the optimum use of these agents.
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PMID:Bisphosphonates in the treatment of disorders of mineral metabolism. 767 Oct 99

Bisphosphonates are being used in disorders associated with accelerated resorption of bone, particularly Paget's disease of bone and the bone disease of malignancy. Their undoubted biological efficacy and relatively low apparent toxicity make them attractive candidates for the management of osteoporosis. The bisphosphonate alendronate has many characteristics which suggest that it is suitable for use in osteoporosis. It is a potent inhibitor of osteoclast-mediated bone resorption with no adverse effect on the mineralization of bone. Earlier studies have shown it to be one of the most active bisphosphonates in Paget's disease and the hypercalcemia of malignancy. In common with other bisphosphonates tested thus far, alendronate appears to inhibit bone loss in a variety of experimental models of osteoporosis. Long-term studies are needed to determine its steady-state effects on bone mass in man. Most data indicate that alendronate is capable at least of decreasing the rate of bone loss, and might even induce increments in bone mass for many years. Since the experimental studies show that the increase in bone mass observed with alendronate is associated with an increase in bone strength, its use is likely to decrease the frequency of fractures. However, direct clinical evidence for this requires the outcome of well-designed long-term prospective studies.
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PMID:Rationale for the use of alendronate in osteoporosis. 770 18

Hypercalcemia of malignancy is due either to local osteolysis at the site of bone metastases or to production by the malignancy of parathyroid hormone-related peptide, which shares some of the effects of parathyroid hormone. We used a radioimmunoassay (antiserum specific to the amino-terminus) to measure serum parathyroid hormone-related peptide levels in controls (n = 61), chronic renal failure patients (n = 10), patients with primary hyperparathyroidism (n = 19), cancer patients with (n = 35) or without (n = 57) hypercalcemia and/or bone metastases (n = 53 and n = 39, respectively), and patients with hematologic malignancies (n = 15). We set the upper limit of normal of the parathyroid hormone-related peptide assay at 2.7 pmol/L. The peptide was undetectable in two-thirds of healthy controls. Renal failure did not interfere with the assay. Eighteen of the 19 patients with primary hyperparathyroidism had normal levels. In contrast, 82% of patients with humoral hypercalcemia of malignancy (i.e., without detectable bone metastases) had increased levels; in this subgroup there was a significant inverse correlation between serum levels of the peptide and phosphorus. Elevation of parathyroid hormone-related peptide levels was less common among hypercalcemic patients with metastatic bone disease (38%). Four of the seven hypercalcemic patients with hematologic malignancies had elevated parathyroid hormone-related peptide levels. In our overall study population, serum calcium levels were weakly but significantly correlated with parathyroid hormone-related peptide levels. In conclusion, elevated parathyroid hormone-related peptide in a patient with hypercalcemia suggests a malignant disease.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Contribution of parathyroid hormone-related peptide to the evaluation of hypercalcemia. 778 31

The bisphosphonates have been investigated over the past two decades for the treatment of various diseases of bone and calcium metabolism that are characterized by increased bone resorption, including osteoporosis, Paget's disease, primary hyperparathyroidism, hypercalcemia of malignancy and metastatic bone disease. The bisphosphonate alendronate was recently approved by the U.S. Food and Drug Administration as a therapy for postmenopausal osteoporosis. This agent is currently the bisphosphonate of choice for clinical use. In postmenopausal osteoporosis, alendronate has been shown to increase bone mineral density and to decrease the rate of new fractures. Adverse effects are not usually a problem when 10 mg per day of alendronate is given with at least 6 oz of water 30 minutes before ingestion of the first food or beverage of the day.
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PMID:Alendronate: a bisphosphonate for treatment of osteoporosis. 890 Mar 45

Bisphosphonates are a new theraeutic option in the treatment of bone diseases. They inhibit osteoclastic bone resorption and are established in the treatment of osteoporosis, Paget's disease of bone and especially in tumor bone disease. The effects of pamidronate, clodronate and ibandronate in the treatment of hypercalcemia of malignancy and osteolytic bone disease have been extensively studied. These drugs represent the treatment of choice in hypercalcemia of malignancy. The regular application of bisphosphonates reduces skeletal-related events like pathologic fracture, bone pain or hypercalcemia of malignancy, especially in breast cancer and multiple myeloma. Of great interest are the ongoing studies concerning prophylactic application of bisphosphonates in tumors bearing a high risk for bone metastases, especially since the first results suggest a significant reduction in the development of bone metastases in breast cancer patients.
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PMID:[Biphosphonate therapy in the management of skeletal metastases]. 961 82

BACKGROUND: Bone is the most frequent site of metastasis in patients with breast cancer. Bone metastasis, particularly osteolytic bone destruction, is usually associated with significant morbidity and deterioration of quality of life. Bisphosphonates are specific inhibitors of osteoclast activity used in the treatment of hypercalcemia of malignancy and osteolytic bone disease. METHODS: We reviewed pertinent literature on the use of bisphosphonates therapy to treat metastatic breast cancer. RESULTS: The use of bisphosphonates in the management of osteolytic bone metastases results in improved palliation of symptoms. Use of these agents in the adjuvant setting may help to prevent bone metastases. CONCLUSIONS: Bisphosphonates represent an effective palliative treatment when combined with chemotherapy and hormonal therapy for the management of osteolytic bone metastases. Identifying the exact mechanism of action requires further investigation to better define the possibility of a direct antitumor effect. The role of bisphosphonates in the adjuvant setting is still controversial, pending the results of large randomized trials.
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PMID:Bisphosphonates in the Management of Breast Cancer. 1075 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


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