Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: KEGG:D01968 (Zoledronic acid)
 505 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Deterioration of bone health is a major concern during progression and treatment of patients with breast cancer, especially in postmenopausal women. Disease- and treatment-associated skeletal-related events include fractures, spinal compression, bone pain, and hypercalcemia of malignancy. Bisphosphonates, which inhibit osteoclastic bone resorption, are important new agents in the management of skeletal-related events, and their impact on breast cancer-related bone metastases and on bone loss during long-term estrogen deprivation therapies such as aromatase inhibitors is reviewed. Intravenous pamidronate has become the standard bisphosphonate to reduce or delay skeletal complications of advanced breast cancer bone metastases, but the more potent agent, zoledronic acid, appears to be at least as effective. Another agent, ibandronate, is also active but has not been investigated in comparison with the other intravenous bisphosphonates. Zoledronic acid is the most convenient to administer, requiring only a short infusion. The effects of bisphosphonates on bone health in women with early breast cancer are also being investigated. A single yearly infusion of zoledronic acid has been shown to significantly increase bone mineral density in osteoporotic postmenopausal women and to reduce biochemical markers of bone turnover. The possibility of such treatment-reversing aromatase inhibitor-associated bone loss during adjuvant therapy of breast cancer is being evaluated in a trial of letrozole, with zoledronic acid added initially or after the onset of bone loss or fracture.
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PMID:Optimizing bisphosphonate therapy in patients with breast cancer on endocrine therapy. 1571 98

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

Intervenous (IV) bisphosphonates are used for cancer patients with hypercalcemia of malignancy (HCM) and breast cancer bone metastases (BM). Recently, zoledronic acid, the most potent third generation bisphosphonate, has been approved for both HCM and BM of broad tumors. It showed 850-fold stronger activity than pamidronate in bone resorption assay, and clinical efficacy against multiple cancer bone lesion has been confirmed in randomized clinical trials. Zoledronic acid becomes one of the most used bisphosphonate for cancer patients in the world, and the results of clinical trials for cancer treatment-induced bone loss or postmenopausal osteoporosis are now updating.
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PMID:[Therapeutic agents for disorders of bone and calcium metabolism: Zoledronic acid]. 1721 Oct 90

Zoledronic acid has been marketed for the past 5 years for the treatment of hypercalcemia of malignancy and malignant bone disease in patients with multiple myeloma or a broad range of solid tumors. The safety profile of zoledronic acid in this patient population is well established from the databases of several large, randomized, Phase III trials and postmarketing clinical experience. Zoledronic acid is well tolerated, with predictable side effects, primarily transient flu-like symptoms, which are manageable with standard treatment. Renal monitoring is recommended, with dose reductions for patients with renal dysfunction. Monitoring for electrolyte imbalance is also important as is calcium and vitamin D supplementation. Ocular complications are rare, and osteonecrosis of the jaw is uncommon and might be avoidable with appropriate dental care.
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PMID:The safety of zoledronic acid. 1748 Jan 79

Lung cancer is one of the most common cancers diagnosed worldwide. As the disease progresses, patients with lung cancer can develop metastasis to the bone. However, because early-stage bone disease may be asymptomatic, bone metastases often go undiagnosed, resulting in delayed initiation of treatment to prevent skeletal complications. In the absence of bone-targeted therapies, patients with metastatic bone disease are at increased risk for potentially debilitating skeletal-related events (SREs) including pathologic fracture, spinal cord compression, hypercalcemia of malignancy, and the requirement for surgery or radiation therapy to bone. The majority of patients with bone metastases from lung cancer will develop SREs, and this number is expected to increase with the improvement of primary therapies that are prolonging the lives of patients. Zoledronic acid is the only bisphosphonate that has been extensively studied in patients with bone metastases from lung cancer, and it has demonstrated efficacy in delaying the onset and reducing the risk of SREs in this setting. Preventing SREs with zoledronic acid may preserve the quality of life and functional independence of these patients. Recent exploratory analyses of a phase III study in patients with bone metastases from lung cancer or other solid tumors revealed that zoledronic acid also normalizes biochemical markers of bone metabolism and may also improve survival in specific patient subsets. Additional ongoing clinical trials are assessing further benefits and antitumor activity of zoledronic acid in the adjuvant setting in the prevention of bone metastases in patients with lung cancer.
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PMID:Skeletal disease contributes substantially to morbidity and mortality in patients with lung cancer. 1963 38

Bisphosphonates are the standard of care for preventing skeletal morbidity and treating hypercalcemia of malignancy in patients with bone metastases. Zoledronic acid (intravenous; 4 mg monthly) is approved to prevent skeletal-related events (SREs) in patients with bone metastases from several tumor types, and can improve survival in some subsets of patients with skeletal metastases and high baseline bone turnover. In the adjuvant setting, bisphosphonates have shown clinical efficacy for preventing cancer treatment-induced bone loss and promise for reducing disease recurrence. For example, early studies of clodronate showed the potential for bisphosphonates to prevent bone metastases and prolong survival, but results with clodronate have been inconsistent. Recently, the more active bisphosphonate zoledronic acid (4 mg every 6 months) prevented bone loss and significantly reduced the risk of disease-free survival events by 36% (P = .01) compared with adjuvant endocrine therapy alone in a large phase III trial (N = 1,803) in premenopausal women with early breast cancer. Notably, these benefits were not limited to bone, because the addition of zoledronic acid reduced disease recurrence at all sites. Similarly, twice-yearly zoledronic acid has reduced disease recurrence in large phase III trials in more than 1,600 postmenopausal women with early breast cancer. Several ongoing trials (involving more than 20,000 patients altogether) are evaluating the efficacy of bisphosphonates for prevention of metastases in breast, prostate, and lung cancers; and multiple myeloma. Results from these studies are likely to expand the role of bisphosphonates, especially zoledronic acid, in the adjuvant therapy setting.
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PMID:Bisphosphonates in the prevention of disease recurrence: current results and ongoing trials. 2002 70

Zoledronic acid is a newly FDA-approved bisphosphonate for the treatment of hypercalcemia of malignancy. Although the safety and efficacy of this drug in treating hypercalcemia associated with hyperparathyroidism have not yet been established in clinically controlled trials, its off-label use is not uncommon. We describe a patient with primary hyperparathyroidism treated with zoledronic acid who developed severe postoperative hypocalcemia. A 64-yr-old woman was admitted with severe hypercalcemia. She was treated with rehydration, calcitonin, methylprednisolone, furosemide as well as 4 mg/day of zoledronic acid for two consecutive days. Primary hyperparathyroidism caused by a right inferior parathyroid lesion was diagnosed. While awaiting surgery, she continued furosemide, methylprednisolone and hydration: after one week, serum calcium had fallen to such a low level that a short-term calcium carbonate supplementation was required. Three weeks after admission, the patient underwent selective right inferior parathyroidectomy, followed by reduction of PTH. During the postoperative period the patient presented severe hypocalcemia resistant to the usual treatment. Serum calcium levels returned to normal three months after surgery. The severity of hypocalcemia and the resistance to conventional treatments suggest that the effect of hungry bone syndrome could be worse in patients treated with bisphosphonates in the preoperative phase.
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PMID:Post-surgery severe hypocalcemia in primary hyperparathyroidism preoperatively treated with zoledronic acid. 2111 66

A 61-year-old woman presented with acute pain of the right thigh after falling on a public street. She had been diagnosed with metastatic breast cancer and bisphosphonate therapy along with zoledronic acid. Radiographs demonstrated transverse subtrochanteric femoral fracture with thickening of the lateral cortex and spike of the medial cortex at the site of fracture. The contralateral femur showed thickening of the lateral cortex at the same site. This type of stress fracture is related to severe suppression of bone turnover (SSBT) under bisphosphonate therapy. Our patient had been receiving zoledronic acid therapy for 3.6 years, and the radiographic findings were typical of stress fracture associated with bisphosphonate. Therefore, the facture in our patient was considered related to SSBT under zoledronic acid therapy. Zoledronic acid is administered to patients with osteoporosis or complications due to cancer such as hypercalcemia of malignancy. Recently stress fractures associated with zoledronic acid therapy for osteoporosis have attracted attention. However, there are few reports of fracture associated with zoledronic acid therapy for cancer. Doses of zoledronic acid recommended for cancer patients are much greater than those for patients with osteoporosis. Clinicians treating such cancer patients need to cautiously manage stress fractures as a complication of zoledronic acid therapy.
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PMID:Subtrochanteric fracture in a patient receiving zoledronic acid therapy for metastatic breast cancer. 2192 3

Zoledronic acid (ZOL) is a new generation bisphosphonate with improved efficacy benefits over pamidronate in preclinical testing. In addition, ZOL is superior to pamidronate in the treatment of hypercalcemia of malignancy. ZOL is also the first bisphosphonate to demonstrate efficacy in patients with bone metastases from solid tumors other than breast cancer, such as prostate cancer. In this study, we investigated ZOL treatment in 17 Japanese men with advanced prostate cancer, treated at the Aichi Medical University Hospital between August 2006 and November 2007. The 17 patients had biopsy-confirmed prostate cancer and were found to harbor bone metastasis upon bone scintigraphy. ZOL was administered intravenously at a dose of 4 mg over 15 min every 4 weeks. ZOL was well tolerated with mild renal dysfunction in 2 patients (11.8%), while 1 patient (5.8%) developed skin rash. No significant side effects were observed. Subjective improvement in bone pain was reported in 14 patients (32.4%). ZOL, therefore, is a safe and effective drug that remains an important component of the urologist's armamentarium against advanced prostate cancer.
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PMID:The use of zoledronic acid in Japanese men with stage D2 prostate cancer. 2296 48

Zoledronic acid (ZA) administration has been associated with electrolyte abnormalities, including hypocalcemia, hypomagnesemia, hypokalemia, and hypophosphatemia. We describe a case of severe, refractory hypophosphatemia in a patient who received ZA for hypercalcemia of malignancy (HCM). Little data are available that describe the incidence or degree of severity of hypophosphatemia that can occur following ZA administration. In addition, no formal recommendations exist to guide monitoring for or management of electrolyte derangements in the setting of bisphosphonate use. Our patient required daily, high-dose phosphorus replacement beginning day 4 following ZA administration. The average daily dose of phosphorus, including both intravenous and enteral administration, was highest in the first 2 weeks after ZA, averaging 77 mmol/d days 4 through 15, and does not include sources of phosphorus from the patient's nutrition support. Despite this high amount of supplementation, which was well beyond what meets normal daily requirements and the amount expected to treat "usual" hypophosphatemia, the patient did not achieve sustained normal serum phosphorus levels for over 30 days after ZA. ZA is a favorable option for treating HCM because of its longer duration of action, potent serum calcium-lowering effects, and favorable safety profile. The risk of hypophosphatemia with ZA use is reviewed.
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PMID:A Case of Severe, Prolonged, Refractory Hypophosphatemia After Zoledronic Acid Administration. 2673 79


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