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)

Preclinical studies with zoledronic acid (Zometa; Novartis Pharmaceuticals Corp, East Hanover, NJ) have shown its potential in malignant bone disease. Clinical studies in the 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 ongoing to establish the efficacy and safety of zoledronic acid in the treatment of osteolytic and osteoblastic bone metastases. In one study, 4 mg zoledronic acid is compared with the standard therapy, 90 mg pamidronate, in treatment of osteolytic lesions in patients with breast cancer and multiple myeloma. Two other studies, one in patients with prostate cancer and bone metastases and another in patients with non-small cell lung cancer and other tumor types, are placebo-controlled. The primary end point in all three studies is the frequency of skeletal complications resulting from bone metastases. Adjuvant trials that assess the ability of zoledronic acid to prevent or reduce the incidence of bone metastases in patients at high risk for future skeletal metastasis are also planned or ongoing. The rationale and design of these ongoing and planned studies is discussed.
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PMID:The role of zoledronic acid in cancer: clinical studies in the treatment and prevention of bone metastases. 1134 60

Bone metastases represent a significant tumor-related complication affecting many breast cancer patients. The resulting bone destruction or osteolysis that frequently accompanies metastatic bone disease results in considerable morbidity for patients including a high rate of skeletal complications, severe pain, and a reduced quality of life. Traditionally, the treatment of metastatic bone disease has relied heavily on the use of multidisciplinary therapies, such as radiotherapy in combination with systemic treatment, supported by analgesia. Bisphosphonates are a class of pyrophosphate analogs that actively inhibit bone resorption. As a result, their clinical application has expanded greatly over the past 5 to 10 years and, in addition to being the treatment of choice for hypercalcemia of malignancy, they have been shown to be effective in reducing the skeletal morbidity associated with metastatic breast cancer. Furthermore, recent data from animal and in vitro studies suggest that bisphosphonates may actually have an antiapoptotic and antiproliferative effect not only on osteoclasts, but also on macrophages and tumor cells. Recent improvements in our understanding of the underlying molecular mechanisms in breast cancer, the diagnosis of the disease itself, and the development of new systemic therapies has led to improved survival benefit for many breast cancer patients. However, because survival duration has also been related to the risk of developing skeletal complications, bisphosphonates may play an ever greater role in the management and prevention of skeletal morbidity in the future.
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PMID:Factors influencing the role of bisphosphonates in breast cancer management. 1154 75

Calcitonin was originally discovered as a hypocalcemic factor synthesized by thyroid parafollicular C cells. Early experiments demonstrated that calcitonin inhibited bone resorption and decreased calcium efflux from isolated cat tibiae and subsequent histologic and culture studies confirmed the osteoclast as its major site of action. Its potent antiresorptive effect and analgesic action have led to its clinical use in treatment of Paget's bone disease, osteoporosis, and hypercalcemia of malignancy. This review surveys the cellular and molecular basis of these physiologic and clinical actions.
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PMID:Calcitonin: the other thyroid hormone. 1248 44

The skeleton is the most common organ to be affected by metastatic cancer. Hypercalcemia of malignancy (HM) affects 10 to 20% of patients with advanced cancer. HM causes a series of symptoms, constipation, nausea and vomiting, confusion and/or stupor, polyuria and polydipsia, bone pains, which decrease quality of life. The normalization of calcemia significantly improves all these symptoms. Despite that, HM remains largely underdiagnosed and undertreated. HM is an emergency. Treatment of HM includes rapid rehydration of isotonic saline and i.v. bisphosphonates. Complications from metastatic bone disease include pathological fracture, HM, spinal cord compression, bone marrow infiltration, pain, and reduced mobility. Treatment with bisphosphonates are effective to reduce these complications. They should be started when bone metastases are diagnosed and continue until it is no longer clinically relevant. The most currently used bisphosphonates were clodronate and pamidronate. The increase convenience of a 15 minutes infusion, the greater efficacy and longer duration of response makes zoledronate the standard of care for HM and metastatic bone disease.
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PMID:[Bisphosphonates in malignant hypercalcemia and bone pain]. 1509 27

Ibandronate is a potent nitrogen-containing bisphosphonate. It has a strong affinity for bone mineral and potently inhibits osteoclast-mediated bone resorption. Ibandronate is effective for the treatment of hypercalcemia of malignancy, metastatic bone disease, postmenopausal osteoporosis, corticosteroid-induced osteoporosis, and Paget's disease. Oral ibandronate is rapidly absorbed (t(max) < 1 hour), with a low bioavailability (0.63%) that is further reduced (by up to 90%) in the presence of food. Ibandronate has a wide therapeutic index and is not metabolized and, therefore, has a low potential for drug interactions. Given its metabolic stability, ibandronate is eliminated from the blood by partitioning into bone (40%-50%) and through renal clearance (CL(R) approximately 60 mL/min). The CL(R) of ibandronate is linearly related to creatinine clearance. The sequestration of ibandronate in bone (V(D) > 90 L) results in a multiphasic elimination (t((1/2)) range approximately 10-60 hours), characterized by the slow release of ibandronate from the bone compartment. The potency of ibandronate and its sequestration into bone allow ibandronate to be developed as oral and intravenous injection formulations that can be administered with convenient extended between-dose intervals.
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PMID:Ibandronate: a clinical pharmacological and pharmacokinetic update. 1531 23

Metastatic bone disease puts an enormous burden on patients and health care resources. Disruption of normal bone homeostasis by bone metastases leads to troublesome skeletal complications, such as bone pain, pathologic fractures, hypercalcemia of malignancy, and spinal cord compression. Bisphosphonates are an effective treatment for skeletal complications. These agents act primarily by initiating biochemical processes that ultimately result in apoptosis of osteoclasts, but they also have a number of other antitumor functions (eg, inhibition of angiogenesis). At present, the most widely used bisphosphonates are oral clodronate and intravenous pamidronate and zoledronic acid. Although these agents are effective in reducing skeletal complications, they are associated with varying safety and convenience issues. More recently, the availability of ibandronate as intravenous and oral formulations represents a new alternative for the treatment of metastatic bone disease. Further studies are necessary to establish the comparative benefits of bisphosphonates in metastatic bone disease.
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PMID:Bisphosphonates in the treatment of skeletal metastases. 1549 Mar 77

Bisphosphonates possess a fundamental role in the treatment of bone metabolic diseases. Yet their main limitations are poor oral absorption and gastrointestinal side effects, mainly esophageal irritation. Indeed, oral administration is unpleasant for many patients, and it is difficult in bed-confined subjects. Therefore, intravenous administration of these agents can be very useful in several clinical scenarios, especially to improve the compliance. Recently, it has been showed that intravenous bisphosphonates are very useful to control hypercalcemia of malignancy, and to prevent bone complications related to metastases. Their use has also been analyzed in the prevention of bone disease after organ transplantation. Thus, their application to control Paget's disease of bone is well-known, and probably they could have an important role as antiresorptive agents in postmenopausal and steroidal osteoporosis. We present here a state of the art of the use of intravenous bisphosphonates for the aforementioned disorders.
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PMID:[Intravenous bisphosphonates]. 1576 Jun 4

Biophosphonates are analogues of pyrophosphate. The mechanism of action of bisphosphates is the inhibition of osteoclast activation (antiresorptive mechanism). The oral bioavailability of biophosphonates is only about 1-2%, and because of gastrointestinal side effects (mainly esophageal irritation), oral agents are less useful in oncology. Biophosphonates are used for the treatment of Paget s disease of bone, the prevention of osteoporosis, and in another clinical scenarios as the prevention of bone disease after organ transplantation. In clinical oncology biophosphonates are used for the treatment of hypercalcemia of malignancy, prevention and treatment of bone events related to bone metastases, and in the prevention of osteoporosis related to breast cancer. According to American Society of Clinical Oncology (ACO) guidelines, biophosphonates should be used in hypercalcemia of malignancy and bone events related to metastases of breast cancer and multiple myeloma.
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PMID:[Biphosphonates in oncology]. 1645 91

Multiple myeloma is the malignant proliferation of plasma cells involving more than 10% of the bone marrow. The bone complications associated with multiple myeloma include bone pain, pathologic fractures, hypercalcemia of malignancy and cord compressions. The principal pathophysiology of bone disease in multiple myeloma is a shift in the balance of bone remodeling toward bone resorption. In recent years, bisphosphonates have become an important treatment for the bone complications of multiple myeloma. Potent inhibitors of osteoclast activity, bisphosphonates interfere with biochemical pathways and induce osteoclast apoptosis. Bisphosphonates also antagonize osteoclastogenesis and promote differentiation of osteoblasts, as well as inhibiting other aspects of osteoclast homeostasis and metabolism. Several studies have evaluated treatment with bisphosphonates in patients with multiple myeloma, and have demonstrated the efficacy of clodronate (Bonefos; Anthra Pharmaceuticals; Princeton, NJ; www.bonefos.com), pamidronate (Aredia; Novartis Pharmaceuticals Corp; East Hanover, NJ; www.pamidronate.com) and zoledronic acid (Zometa; Novartis Pharmaceuticals Corp; East Hanover, NJ; www.us.zometa.com) in reduction of pain, reduction of SREs and survival. Moreover, recent data suggest direct and indirect antimyeloma activity of pamidronate and zoledronic acid.
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PMID:Bone complications in multiple myeloma. 1696 19

Bisphosphonates are effective inhibitors of osteoclast activity and bone resorption, and are standard treatments for osteoporosis, hypercalcemia of malignancy, and metabolic bone disease. Bisphosphonates have also been established to effectively reduce skeletal-related events due to malignancy metastatic to bone. Bisphosphonates are now being incorporated into breast cancer treatment regimens in order to combat osteoporosis caused by ovarian suppression, chemotherapy treatment, aromatase inhibitors and the postmenopausal state itself. A large body of evidence suggests that African-American women are at higher risk for osteoporosis-related morbidity than their Caucasian counterparts. In this review, we highlight recommendations toward screening for osteoporosis in high-risk populations. We summarize the mechanisms of action of bisphosphonates in the treatment of osteoporosis and then summarize national recommendations toward incorporating the use of bisphosphonates as support for the bone health of breast cancer patients, as well as patients at high risk for osteoporosis.
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PMID:Bisphosphonate therapy for women with breast cancer and at high risk for osteoporosis. 1730 67


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