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 (BP) prevent, reduce, and delay cancer-related skeletal complications in patients, and have substantially decreased the prevalence of such events since their introduction. Today, a broad range of BP with differences in potency, efficacy, dosing, and administration as well as approved indications is available. In addition, results of clinical trials investigating the efficacy of BP in cancer treatment-induced bone loss (CTIBL) have been recently published. The purpose of this paper is to review the current evidence on the use of BP in solid tumours and provide clinical recommendations. An interdisciplinary expert panel of clinical oncologists and of specialists in metabolic bone diseases assessed the widespread evidence and information on the efficacy of BP in the metastatic and nonmetastatic setting, as well as ongoing research on the adjuvant use of BP. Based on available evidence, the panel recommends amino-bisphosphonates for patients with metastatic bone disease from breast cancer and zoledronic acid for patients with other solid tumours as primary disease. Dosing of BP should follow approved indications with adjustments if necessary. While i.v. administration is most often preferable, oral administration (clodronate, IBA) may be considered for breast cancer patients who cannot or do not need to attend regular hospital care. Early-stage cancer patients at risk of developing CTIBL should be considered for preventative BP treatment. The strongest evidence in this setting is now available for ZOL. Overall, BP are well-tolerated, and most common adverse events are influenza-like syndrome, arthralgia, and when used orally, gastrointestinal symptoms. The dose of BP may need to be adapted to renal function and initial creatinine clearance calculation is mandatory according to the panel for use of any BP. Subsequent monitoring is recommended for ZOL and PAM, as described by the regulatory authority guidelines. Patients scheduled to receive BP (mainly every 3-4 weeks i.v.) should have a dental examination and be advised on appropriate measures for reducing the risk of jaw osteonecrosis. BP are well established as supportive therapy to reduce the frequency and severity of skeletal complications in patients with bone metastases from different cancers.
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PMID:Guidance on the use of bisphosphonates in solid tumours: recommendations of an international expert panel. 1790 99

Women with advanced breast cancer often develop bone metastases that are associated with skeletal-related events (SREs), which reduce quality of life and increase the risk of death. Because patients who experience one SRE are more likely to experience subsequent events, the goal of therapy is to preserve quality of life by delaying the onset of the first SRE and reducing the incidence of subsequent SREs. Bisphosphonates are used for clinical management of malignant bone disease, and data suggest that early treatment (e.g., before bone pain) may confer additional clinical benefit. Furthermore, data from subsets of zoledronic acid trials suggest that long-term bisphosphonate therapy may provide sustained clinical benefit throughout the disease course. Bisphosphonates are generally safe and well tolerated; adverse events are more often mild and transient. Zoledronic acid has proven efficacy for reducing risk of SREs, and ongoing studies are under way to evaluate customized treatment schedules.
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PMID:Bisphosphonates: reducing the risk of skeletal complications from bone metastasis. 1803 44

Patients with metastatic bone disease are at risk for developing skeletal-related events that can negatively influence quality of life, contributing to loss of autonomy and functional capabilities. Bisphosphonates have become an important component in the treatment of patients with bone metastases as they delay the onset and reduce the risk of skeletal-related events and also palliate or control bone pain in multiple cancer types, thus preserving quality of life. Zoledronic acid has proven efficacy and safety in patients with bone lesions from breast cancer, prostate cancer, lung cancer, and other solid tumors, as well as in patients with multiple myeloma. Current data suggest that early treatment with zoledronic acid (before the onset of bone pain) may provide additional clinical benefits and also positive effects on survival in subsets of patients who have elevated levels of N-telopeptide of type I collagen (NTX), a biochemical marker of bone resorption. Studies have shown that in patients with breast cancer, prostate cancer, lung cancer, or other solid tumors, normalization of elevated levels of NTX was observed in the majority of patients who received zoledronic acid. Furthermore, normalization of NTX values correlated with extended survival.
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PMID:Clinical benefits and considerations of bisphosphonate treatment in metastatic bone disease. 1806 86

Nitrogen-containing biphosphonates are a group of medications that are increasingly used in the management of Paget's disease, fibrous dysplasia, osteoporosis, multiple myeloma and metastatic prostate or breast cancer bone disease. On 2004 it was established that nitrogen-containing biphosphonates may induce jaw osteonecrosis and since then, a substantial number of publications has supported this finding. Jaw osteonecrosis may be asymptomatic, lasting for about a year or symptomatic, accompanied with mild or severe pain. Jaw osteonecrosis usually results in patients with poor dental hygiene, or subjected to invasive dental procedures. Its incidence increases with the length of nitrogen-containing biphosphonates treatment and appears to be higher for the Zometa(TM) users. It is important to early recognize this entity, since early intervention can make a significant difference to the outcome of this debilitating side effect. We here report three patients who had a positive technetium-99m methylene diphosphonate ((99m)Tc-MDP) bone scan. One of these patients also had osteomyelitis and was treated aggressively. The other two were treated in a more conservative manner. Detailed dental examination supported the scintigraphic findings. Biopsy was performed only in one patient and also offered specimens for antibiotic cultures. In discussion, jaw biopsy is a debatable procedure in the setting of jaw osteonecrosis and many consider that it should be avoided in most cases, except if it is necessary to establish the diagnosis and suggest antibiotic treatment by obtaining samples for bacterial cultures. Although axial tomography and magnetic resonance imaging are useful in defining the extent of the disease, 3-phase (99m)Tc-MDP bone scan is the most sensitive imaging modality pinpointing the disease at its early stages. In conclusion, a 3-phase (99m)Tc-MDP scan with anterior and lateral views of the skull is indicated in all symptomatic or asymptomatic patients, with a history of long-term nitrogen-containing biphosphonate treatment, since this may lead to an early detection of the disease.
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PMID:Jaw uptake of technetium-99 methylene diphosphonate in patients on biphosphonates: a word of caution. 1808 61

Many solid tumors metastasize to bone, leading to debilitating skeletal complications such as intractable bone pain and pathologic fractures. Patients who experience a skeletal-related event (SRE) are at higher risk for subsequent events. After an SRE such as a pathologic fracture, spinal cord compression, or the requirement for orthopedic surgery or palliative radiation therapy, a patient's quality of life and functional independence could decline substantially. Prevention or delay of skeletal complications provides clinical benefit to patients with bone metastases secondary to solid tumors. Treatment for the prevention of the first SRE might substantially improve patients' quality of life, functional independence, and pain throughout the course of their disease. Bisphosphonates have shown a palliative benefit in this setting. In particular, zoledronic acid is the only bisphosphonate that has provided benefits for patients with bone metastases secondary to a broad range of solid tumors. Among patients with metastatic breast or prostate cancer, zoledronic acid has demonstrated significant reductions in pain and skeletal morbidity compared with placebo. Zoledronic acid has also shown significant reductions in skeletal morbidity in patients with lung cancer or other solid tumors compared with placebo. Pamidronate, oral clodronate, and ibandronate compared with placebo have each shown significant benefits in reductions of pain and skeletal complications for patients with metastatic breast cancer. Further improvements in the management of skeletal health in patients with malignant bone disease could be achieved through ongoing bisphosphonate investigations to optimize dose, timing, and duration of treatment.
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PMID:Treatment of bone metastases and bone pain with bisphosphonates. 1863 73

Bone metastases are common in patients with advanced-stage cancer; they can lead to skeletal complications (ie, pathologic fractures, spinal cord compression, tumor-induced hypercalcemia, and severe bone pain) that often require orthopedic surgery or palliative radiation therapy and negatively affect quality of life. The primary role of bisphosphonates for the management of bone metastases in patients with advanced-stage cancer is the prevention of these painful skeletal complications. In placebo-controlled trials, a number of bisphosphonates, including oral clodronate, oral and intravenous (I.V.) ibandronate, I.V. pamidronate, and I.V. zoledronic acid, have been shown to significantly reduce skeletal complications in patients with bone metastases from breast cancer. Furthermore, zoledronic acid provided benefit compared with pamidronate in patients with bone metastases from breast cancer in a large, comparative trial. Zoledronic acid also provided long-term benefits in randomized placebo-controlled trials in patients with bone metastases from prostate cancer, lung cancer, and other solid tumors, whereas other bisphosphonates that have been investigated have failed to demonstrate objective long-term benefits in placebo-controlled trials. In addition, although systemic analgesics and radiation therapy are primary treatments for the management of bone pain, bisphosphonates can also play an important secondary role in reducing bone pain associated with skeletal metastases. Notably, several economic analyses of bisphosphonate therapy have demonstrated that these agents are cost-effective by reducing health-care costs associated with skeletal complications and providing clinically significant quality of life benefits to patients with malignant bone disease.
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PMID:Role of bisphosphonates for the management of skeletal complications and bone pain from skeletal metastases. 1863 88

Many patients with advanced cancer experience decreased bone strength due to metastatic foci, underlying osteoporosis and/or cancer treatment induced bone loss. The clinical consequences of metastatic disease involving the skeleton are widespread. This review focuses on the efficacy, pharmacology, and safety when using intravenous biphosphonate such a zoledronic acid for cancer bone metastases. Zoledronic acid is the gold standard for the medical management of metastatic bone disease. The indications for treatment include prevention of skeletal relevant events (SRE), osteoporotic complications, and palliation of bone pain, among others. Zoledronic acid is the only bisphosphonate effective in decreasing SREs associated with bone metastases from advanced renal cell carcinoma and prostate cancer. Regarding prostate cancer, zoledronic acid effectively prevents both bone loss in patients with locally advanced disease receiving androgen deprivation therapy and SREs in men with hormone-refractory or hormone-sensitive metastatic disease. Zoledronic acid has an acceptable safety profile and tolerability, and has been effective at significantly decreasing the incidence, delaying the onset, and reducing the overall risk of experiencing an SRE compared to placebo. It is the only bisphosphonate currently approved for the prevention and treatment of skeletal complications in patients with bone metastases due to all solid tumors.
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PMID:Zoledronic acid in the management of metastatic bone disease. 1872 15

Bisphosphonates (BPs), as inhibitors of osteoclasts, are widely used in the management of metastatic bone disease and in the prevention of osteomalacia and osteoporosis. Recent cases of bone necrosis of the jaws have been associated with the use of bisphosphonate therapy. A case is presented of a patient with osteonecrosis of the maxilla with a history of long-term bisphosphonate therapy for metastatic breast cancer. The authors treated the patient and suggest appropriate patient management guidelines with reference to current knowledge. Although a definitive treatment for bisphosphonate-associated osteonecrosis has not yet been established, clinicians must be aware of the pharmacologic properties of several bisphosphonates currently available and their indications, susceptible risk factors in the development of osteonecrosis of the jaws, the clinical signs and symptoms, and recommendations for patient management, including prevention and early recognition. BPs, potent inhibitors of osteoclast-mediated bone resorption, were first introduced more than 20 years ago. Since then, they have been used widely in the management of bone diseases, including hypercalcemia related to malignancy, myeloma-related bone disease, Paget's disease and osteoporosis. They have also been shown to inhibit tumor cell proliferation and inhibit angiogenesis. These additional features have made BPs useful in the treatment of metastatic disease, including breast and prostate cancer, resulting in a rise in the medical use of these drugs. However, recent reports suggest that BPs, particularly the nitrogen-containing BPs pamidronate (Aredia) and zoledronic acid (Zometa), both manufactured by Novartis of East Hanover, NJ, are capable of causing bisphosphonate-associated osteonecrosis of the jaw (BON). With 2.5 million patients treated with pamidronate and/or zoledronate worldwide, BON occurs in about one per 10,000 treated patients (Novartis, unpublished data, 2004). Currently, the total number of reported cases associated with alendronate (Fosamax, Merck and Co. Inc., White-house Station, NJ) the most commonly prescribed oral bisphosphonate, is approximately 170 worldwide (C. Arsver, oral communication, March 2006). This corresponds to a spontaneous BON incidence of approximately 0.7 cases per 100,000-years exposure. However, there is insufficient data to determine why the osteonecrosis reported seems to particularly affect the jaw, with a slightly higher rate in the mandible than the maxilla. This report concerns the management of a patient with BON. Information provided includes: the pharmacologic properties of the several bisphosphonates currently available; the pathobiological mechanism; the clinical presentation of the oral lesions; and recommendations for the oral management of patients who have received BP therapy, with consideration of a preventative approach based on current knowledge.
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PMID:Bisphosphonate-associated osteonecrosis: a clinician's reference to patient management. 1876 52

Zoledronic acid 4 mg administered as a 15-minute infusion every 3-4 weeks is effective and well tolerated in the treatment of patients with breast cancer metastatic to bone. It is effective in reducing complications arising from metastatic bone disease in this patient population, with a clinical profile that compares favourably with that of pamidronate. Zoledronic acid administered on a less frequent schedule (every 3-6 months) has also shown potential in preventing cancer treatment-induced bone loss in pre- and postmenopausal women with breast cancer receiving adjuvant hormonal therapy. Preliminary data suggest that zoledronic acid may have antitumour effects, which may reduce the risk of overall disease progression in patients with malignant disease. Thus, zoledronic acid has a well established role as first-line treatment in patients with bone metastases secondary to breast cancer, and may prove useful as a preventive treatment for cancer treatment-induced bone loss or an adjuvant therapy in women with breast cancer.
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PMID:Zoledronic acid: a review of its use in breast cancer. 1909 6

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


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