Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151825 (bone pain)
 3,118 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Patients with advanced breast cancer who develop bone metastases suffer an ongoing risk of skeletal complications that can have a significant impact on their quality of life (QoL). These complications include bone pain, pathologic fractures, spinal cord compression, and hypercalcemia of malignancy (HCM), a potentially life-threatening condition. Treatment options include radiotherapy to palliate bone pain and/or prevent impending fracture, orthopedic surgery to prevent or repair fractures, analgesics, and bisphosphonates, which can significantly reduce the risk of skeletal complications and delay their onset. Of the known bisphosphonates, zoledronic acid is the most potent. Since its regulatory approval in the United States and Europe in 2001, zoledronic acid (4 mg by 15-minute infusion) has become widely used and has replaced pamidronate (90 mg by 2-hour infusion) as the standard of care for treating bone metastases from breast cancer and bone lesions from multiple myeloma. Zoledronic acid has also demonstrated significant long-term benefits in randomized trials in prostate cancer and other solid tumors, whereas other bisphosphonates have failed. In long-term, phase III clinical testing, zoledronic acid provided significant treatment benefits beyond those of pamidronate in patients with breast cancer and demonstrated a safety profile comparable with pamidronate. Therefore, zoledronic acid is now recommended from the first diagnosis of bone metastasis. Other intravenous bisphosphonates include clodronate and ibandronate. Both are approved in Europe, but their efficacy relative to pamidronate and zoledronic acid is not known.
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PMID:Management of bone metastases in breast cancer. 1571 97

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

A 74-year old white man was undergoing treatment with palliative chemotherapy for Stage IV Prostate Adenocarcinoma with multiple osteoblastic metastases. He was started on intravenous Zoledronic acid for reduction of bone pain and prevention of skeletal complication from multiple bone metastases. Four days after intravenous Zoledronic acid, the patient presented to emergency room with complaints of carpopedal spasm and bronchospasm. On admission, serum calcium and albumin was 3.5 mg/dl and 3.7 g/dl respectively. QT interval was more than 500 m sec. The patient was started on intravenous calcium gluconate. He received 174 gm of intravenous calcium for total of 12 days. His serum calcium returned to a normal range in three months with Vitamin D and calcium supplement. Before starting Zoledronic acid therapy, the patient's serum calcium level was 6.9 mg/dl.
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PMID:Zoledronic acid-induced severe hypocalcaemia in a prostate cancer patient with extensive osteoblastic bone metastases. 1577 96

Patients with bone metastases from breast cancer often experience substantial skeletal complications -- including debilitating bone pain -- which negatively affect quality of life. Zoledronic acid (4 mg) has been demonstrated to reduce significantly the risk of skeletal complications in these patients and is administered via a short, 15-min infusion every 3 weeks, allowing the possibility for home administration. This study compared the efficacy and safety of zoledronic acid administered in the community setting vs the hospital setting in breast cancer patients with > or =1 bone metastasis receiving hormonal therapy. After a lead-in phase of three infusions of 4 mg zoledronic acid in the hospital setting, 101 patients were randomized to receive three open-label infusions in the community or hospital setting, followed by three infusions in the opposite venue (a total of nine infusions). The Brief Pain Inventory (BPI) and the European Organisation for Research and Treatment of Cancer Quality of Life Core Questionnaire 30 (EORTC QLQ-C30) were used to assess potential benefits of zoledronic acid therapy. At study end, analysis of the BPI showed significant reductions in worst pain (P=0.008) and average pain in the last 7 days (P=0.039), and interference with general activity (P=0.012). In each case, there were significantly greater improvements in pain scores after treatment in the community setting compared with the hospital crossover setting for worst pain (P=0.021), average pain (P=0.003), and interference with general activity (P=0.001). Overall global health status showed a significant median improvement of 8.3% (P=0.013) at study end. Physical, emotional, and social functioning also showed significant overall improvement (P=0.013, 0.005, and 0.043, respectively). Furthermore, physical, role, and social functioning showed significantly greater improvements after treatment in the community setting compared with the hospital crossover setting (P=0.018, 0.001, and 0.026, respectively). There was no difference between hospital and community administration in renal or other toxicity, with zoledronic acid being well tolerated in both treatment settings. These data confirm the safety and quality-of-life benefits of zoledronic acid in breast cancer patients with bone metastases, particularly when administered in the community setting.
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PMID:Zoledronic acid significantly improves pain scores and quality of life in breast cancer patients with bone metastases: a randomised, crossover study of community vs hospital bisphosphonate administration. 1587 Jul 21

Intravenous bisphosphonates are the preferred treatment to prevent skeletal complications for patients with breast cancer and bone metastases. Pamidronate, a single-nitrogen bisphosphonate, was the early standard of care for such patients based on 2 large, placebo-controlled trials involving 754 patients. Zoledronic acid, a new-generation bisphosphonate containing 2 nitrogens, was evaluated in 1130 patients with breast cancer in a large, randomized, comparative, phase III trial with pamidronate. At 25 months, zoledronic acid (4 mg) significantly reduced the overall risk of developing a skeletal-related event (SRE) by an additional 20% versus 90 mg pamidronate by multiple-event analysis. Furthermore, zoledronic acid was at least as effective as pamidronate in reducing the proportion of patients with > or = 1 SRE and in delaying the onset of SREs. Moreover, a retrospective subset analysis of 352 patients with > or = 1 osteolytic lesion proved zoledronic acid more effective than pamidronate in reducing the risk and delaying the onset of SREs. Intravenous ibandronate (6 mg via 1-2-hour infusion) was evaluated in a placebo-controlled, phase III trial of 466 patients and was significantly more effective than placebo in reducing the number of 12-week treatment periods in which an SRE occurred. The safety profiles among all intravenous bisphosphonates were similar; patients treated with intravenous bisphosphonates reported notably less bone pain but a higher incidence of mild to moderate transient infusion-related adverse events (eg, nausea, vomiting, myalgia, and anorexia) compared with placebo. In summary, intravenous bisphosphonates are effective for the treatment of bone metastases in patients with breast cancer and have similar safety profiles, but the shorter infusion time and greater efficacy of zoledronic acid in reducing overall skeletal morbidity provide advantages over other available agents.
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PMID:Efficacy and safety of intravenous bisphosphonates for patients with breast cancer metastatic to bone: a review of randomized, double-blind, phase III trials. 1600 90

Patients with metastatic bone disease often have severe bone pain and debilitating skeletal complications. Zoledronic acid is the only bisphosphonate shown to be safe and effective in reducing skeletal-related events (SREs), including pathological fractures, spinal cord compression, and radiation or surgery to bone in patients with bone metastases from advanced prostate cancer or renal cell carcinoma (RCC). In both tumour types, zoledronic acid significantly decreased the overall risk of developing an SRE, delayed their onset and significantly reduced the incidence of SREs compared with placebo. In patients with RCC, zoledronic acid also significantly delayed the time to progression of bone lesions by 5 months compared with placebo. Zoledronic acid is safe and well tolerated with long-term use.
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PMID:Zoledronic acid is effective in preventing and delaying skeletal events in patients with bone metastases secondary to genitourinary cancers. 1646 48

Men with prostate cancer are at risk for bone loss and skeletal complications throughout the course of their disease. Bone loss is prevalent in many men with prostate cancer at initial diagnosis, and initiating androgen deprivation therapy results in accelerated bone resorption, leading to bone loss and an increased risk of fracture. These men are also at high risk for disease progression and bone metastases that can result in significant skeletal morbidity, including pathologic fracture, spinal cord compression, and debilitating bone pain requiring additional therapy. Excessive osteoclast activity plays a central role in the pathophysiology of bone disease at each stage of prostate cancer disease progression. Zoledronic acid, a highly potent inhibitor of osteoclast-mediated bone resorption, has increased bone mineral density in men receiving androgen deprivation therapy and is the only bisphosphonate that has shown statistically significant reductions in skeletal morbidity in patients with bone metastases from prostate cancer. Furthermore, preclinical evidence suggests that zoledronic acid has antitumor activity in prostate cancer models. Recently, a treatment algorithm was developed by the 3rd International Consultation on Prostate Cancer recommending the use of zoledronic acid for the prevention of skeletal complications in patients with bone metastases from prostate cancer, regardless of their hormone status, and for the prevention of treatment-induced bone loss in patients without evidence of bone metastases. According to this algorithm, zoledronic acid should be considered for the prevention of skeletal morbidity in patients with prostate cancer throughout their treatment continuum.
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PMID:Rationale for zoledronic acid therapy in men with hormone-sensitive prostate cancer with or without bone metastasis. 1641 86

In 2002/2003 a number of patients presented to the South Australian Oral and Maxillofacial Surgery Unit with unusual non-healing extraction wounds of the jaws. All were middle-aged to elderly, medically compromised and on bisphosphonates for bone pathology. Review of the literature showed similar cases being reported in the North American oral and maxillofacial surgery literature. This paper reviews the role of bisphosphonates in the management of bone disease. There were 2.3 million prescriptions for bisphosphonates in Australia in 2003. This group of drugs is very useful in controlling bone pain and preventing pathologic fractures. However, in a small number of patients on bisphosphonates, intractable, painful, non-healing exposed bone occurs following dental extractions or denture irritation. Affected patients are usually, but not always, over 55 years, medically compromised and on the potent nitrogen containing bisphosphonates pamidronate (Aredia/Pamisol), alendronate (Fosamax) and zolendronate (Zometa) for non-osteoporotic bone disease. Currently, there is no simple, effective treatment and the painful exposed bone may persist for years. The main complications are marked weight loss from difficulty in eating and severe jaw and neck infections. Possible preventive and therapeutic strategies are presented although at this time there is no evidence of their effectiveness. Dentists must ask about bisphosphonate usage for bone disease when recording medical histories and take appropriate actions to avoid the development of this debilitating condition in their patients.
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PMID:The dental implications of bisphosphonates and bone disease. 1641 12

Bone pain and bone deformities are the most common manifestations of Paget's disease of bone, even if the diagnosis is nowadays most often made by chance following a routine measurement of serum alkaline phosphatase. Woven bone is formed following a marked increase in bone resorption due to a stimulation of osteoclast activity. Biphosphonates constitute the modern treatment of Paget's disease of bone. Tiludronate (Skelid), or better risedronate (Actonel), are administered orally every day during at least 2 months. Zoledronic acid (Aclasta), as a single 15-min 5 mg infusion, has been recently compared to risedronate, 30 mg/d orally for 2 months, in two randomized studies including 357 patients. Zoledronic acid had a superior therapeutic efficacy, as judged by its rapidity of action, the duration of the biochemical response and the percentage of responders. Thus, at 6 months, alkaline phosphatase levels were normalized in 89% of the patients in the zoledronic acid group as compared to 58% in the risedronate group. The most frequent side effect was a flu-like syndrome, observed in 10% of the patients. An adequate intake of calcium and vitamin D is recommended to avoid posttreatment hypocalcemia. The introduction of Aclasta should simplify and improve the therapeutic management of Paget's disease of bone.
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PMID:[Treatment of Paget's disease of bone with zoledronic acid]. 1645 55

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


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