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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Metastatic bone disease is a frequent cause of morbidity in advanced cancer patients with a subsequent high incidence of skeletal complications (fractures, hypercalcemia, spinal cord compression) and severe pain. The osteolytic process is mainly characterized by an osteoclastic activity of bone resorption and inflammatory activity provoked by various cytokines and prostaglandins. Bisphosphonates represent a new class of drugs with inhibitory activity on bone resorption and on inflammatory processes which revealed themselves to be efficacious in a series of clinical conditions such as tumour-induced hypercalcemia, Paget's disease, osteoporosis and metastatic bone disease. The aim of this review of the literature is to show the analgesic efficacy of the different bisphosphonates in phase III studies carried out on patients with metastatic bone disease. Medline and Cancerlit database from January 1984 to February 1998 have been considered. From the analysis of the published studies it appears that bisphosphonates and, in particular, intravenous Disodium Pamidronate, are not only able to slow down the progression of the disease and to reduce the onset of skeletal complications but also have an analgesic effect and the possibility of improving the quality of life, above all in patients with osteolytic metastases due to breast cancer and multiple myeloma. Bisphosphonates represent a further valid therapy to add to an already consolidated list of therapies such as radio, chemo and endocrine therapy, analgesic drugs, orthopaedic and physiatric in the pain management of patients with bone metastases. These drugs meet with the patients' compliance, are well-tolerated as well as having a good cost/efficacy profile. It still remains to be seen if the newer and more potent bisphosphonates such as Ibandronate and Zoledronate can be administered differently from the intravenous route such as by mouth or by patch which are readily accepted by the patient and, moreover, if these more potent drugs are able to prevent or delay the onset and/or the progression of bone metastases.
Pain 1998 Dec
PMID:The role of bisphosphonates in the treatment of painful metastatic bone disease: a review of phase III trials. 987 May 69

Bone metastases occur in most women with advanced breast cancer and can lead to considerable morbidity and a rapid deterioration in the patient's quality of life. It was the aim of the present study to assess changes in quality of life and bone pain due to intravenous (i.v.) ibandronate, a potent third-generation bisphosphonate. In a phase III randomised, double-blind, placebo-controlled trial in patients with bone metastases due to breast cancer, 466 women were randomised to receive placebo, 2 mg ibandronate or 6 mg ibandronate for up to 96 weeks. Treatment was administered i.v. at 3- or 4-weekly intervals. Clinical endpoints included the incidence of adverse events, quality of life (assessed using the European Organisation for the Research and Treatment of Cancer (EORTC) Quality of Life Scale - Core 30 questionnaire (QLQ-C30)), and bone pain (assessed on a 5-point scale from 0=none to 4=intolerable). Ibandronate was generally well tolerated. Compared with baseline measurements, the bone pain score was increased at the last assessment in both the placebo and 2 mg ibandronate groups, but was significantly reduced in the patients receiving 6 mg ibandronate (-0.28+/-1.11, P < 0.001). A significant improvement in quality of life was demonstrated for patients treated with ibandronate (P < 0.05) for all global health status. Overall, at the last assessment, the 6 mg ibandronate group showed significantly better functioning compared with placebo (P = 0.004), and had significantly better scores on the domains of physical, emotional, and social functioning, and in global health status (P < 0.05). Significant improvements in the symptoms of fatigue and pain were also observed in the 6 mg ibandronate group. I.v. ibandronate treatment leads to significant improvements in quality of life, and is an effective and well-tolerated palliative treatment in patients with bone metastases due to breast cancer.
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PMID:Improved quality of life after long-term treatment with the bisphosphonate ibandronate in patients with metastatic bone disease due to breast cancer. 1525 Nov 60

The main goals of bisphosphonate therapy are to prevent and treat skeletal events, minimize disability, and relieve pain without increasing the overall burden that bone metastases (and their treatment) place on patients. The ease and convenience of treatment are important to patients, and there are data suggesting that patients prefer oral therapy over intravenous drugs to help them maintain a normal life. Intravenous therapy with zoledronic acid and pamidronate is currently time-consuming; preparation, renal monitoring, infusion, and follow-up use valuable health care resources. Intravenous ibandronate could help alleviate this burden because of its good renal safety profile. Although efficacious, oral clodronate has compliance problems because of multiple dosing, large tablet size, and gastrointestinal tolerability issues. Recent phase III trials of oral ibandronate have shown efficacy similar to that of intravenous ibandronate, with no compliance or tolerability concerns. Ibandronate appears to have several advantages over current therapies that could improve treatment acceptability and reduce the burden of disease on the health care system. Research continues into the efficacy, safety, and pharmacoeconomics of ibandronate.
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PMID:Patient management issues in metastatic bone disease. 1549 Mar 81

Bone is an organ commonly involved in spreading neoplastic disease, especially in multiple myeloma and carcinoma of the breast, prostate and lung. Skeletal stabilisation and pain relief are the main treatment goals in metastatic bone disease. Bisphosphonate treatment inhibits osseous breakdown and is well-established as the current standard therapy for reducing complications of neoplastic bone disease (e.g., pain, fractures and hypercalcaemia). Ibandronate is a third-generation bisphosphonate that has recently been approved for the treatment of bone metastases caused by breast cancer. The oral and intravenous formulations of ibandronate appear to have comparable efficacy. Ibandronate has also been shown to provide significant and sustained relief from metastatic bone pain over 2 years of treatment, improving patient functioning and quality of life. With a favourable long-term safety profile and the added convenience and flexibility offered by its efficacious oral formulation, ibandronate represents a new therapeutic option for metastatic bone disease management.
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PMID:Efficacy and safety of ibandronate in the treatment of neoplastic bone disease. 1550 Mar 81

Localized transient osteoporosis (LTO; bone marrow edema syndrome) is a rare disorder of generally unknown etiology that is characterized by acute onset of disabling bone pain. Treatment options are currently limited and largely ineffective. The locally increased bone turnover and low bone mineral density (BMD) typical of LTO indicate a potential role for bisphosphonate therapy. Ibandronate, a potent nitrogen-containing bisphosphonate, has proven efficacy in the management of postmenopausal osteoporosis and corticosteroid-induced osteoporosis when administered as a convenient intermittent intravenous (i.v.) injection with a between-dose interval of 2 or 3 months. In a study of 12 patients with LTO, ibandronate was administered as an initial 4-mg i.v. dose with a second, optional injection of 2 mg at 3 months. Daily calcium and vitamin D supplements were provided. Pain was measured at baseline and at 1, 2, 3, and 6 months using a visual analog scale (VAS) of 1-10, and BMD was measured at baseline and 6 months. I.v. ibandronate provided rapid and substantial pain relief. The mean (SD) VAS score decreased from 8.4 (1.3) at baseline to 0.5 (0.7) at 6 months, at which time seven patients had achieved complete pain relief. At 6 months, mean lumbar spine BMD had increased by 4.0% (range -0.8 to 7.7%) in the overall population. I.v. ibandronate injection affords advantages over currently available oral and i.v. bisphosphonates and thus offers a promising therapeutic advance in the treatment of LTO.
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PMID:Effective and rapid treatment of painful localized transient osteoporosis (bone marrow edema) with intravenous ibandronate. 1622 5

Metastatic bone disease affects many cancer patients and has a significant disease burden because of complications such as pathologic fractures and severe pain, which affect patient mobility and quality of life. Bisphosphonates are the current standard of care for treating metastatic bone disease. Available agents have shown varying degrees of efficacy in clinical trials, and treatment potential can be limited by efficacy, tolerance, or toxicity issues. Ibandronate (Bondronat); F. Hoffman-La Roche Ltd., Basel, Switzerland, http://www.roche.com) is a highly potent, single-nitrogen bisphosphonate that is available in i.v. and oral formulations. In phase III trials in breast cancer patients, both formulations reduced the incidence of skeletal complications associated with metastatic bone disease and had significant and sustained effects on bone pain and patient quality of life. Open-label studies of loading-dose ibandronate administered over consecutive days suggest it also may be useful for relieving severe or opioid-resistant metastatic bone pain. New trials have been designed or are in progress that may extend the clinical indications of ibandronate for patients with metastatic bone disease.
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PMID:Efficacy of ibandronate in metastatic bone disease: review of clinical data. 1626 7

Ibandronate is an experimental intravenous bisphosphonate under study for the prevention or treatment of osteoporosis and skeletal complications of bone metastases, as well as hypercalcemia of malignancy. To review the data on this drug, PubMed/MEDLINE was searched for pertinent studies in English; data from January 1986-October 2005 were reviewed. In preclinical studies, ibandronate was an extremely potent bisphosphonate compared with its predecessors and was active in all animal models of human postmenopausal and corticosteroid-associated osteoporosis. Similar to other bisphosphonates, ibandronate exhibits antitumor activity and prevents or reduces bone metastases. Forty to fifty percent of the dose is bound to bone; renal clearance of unchanged drug accounts for 70% of total body clearance. Early clinical trials demonstrated efficacy and tolerability of intravenous ibandronate in the prevention or treatment of postmenopausal and corticosteroid-associated osteoporosis when administered once every 3 months. Intravenous ibandronate also reduces skeletal complications of bone metastases, including pain, although the cumulative dose used is much higher than that used in osteoporosis, as the drug is administered every 3-4 weeks. Single doses of intravenous ibandronate are probably also effective in the treatment of hypercalcemia of malignancy. The major tolerability issue with intravenous bisphosphonates is renal safety, thus the drugs generally require infusion (e.g., 0.25 hr for zoledronic acid, 2-24 hrs for pamidronate). However, intravenous ibandronate can be administered by bolus injection over a few minutes without an elevated risk of nephrotoxicity. The experimental intravenous dosage is 2 mg every 3 months for treatment or prevention of osteoporosis, and 2-6 mg every 3-4 weeks or in a single dose for treatment of bone metastases or hypercalcemia of malignancy, respectively. Ibandronate can be used in the presence of severe renal impairment with proper dosage adjustment. The drug will be an interesting addition to the available drugs for osteoporosis, bone metastases, and hypercalcemia of malignancy. Studies of intravenous ibandronate as an adjunctive treatment for cancers that tend to metastasize to bone are under way. Whether intravenous ibandronate will be a therapeutic advance is best answered by randomized, controlled trials. These are ongoing and should provide data with which to make better-informed choices concerning intravenous bisphosphonates.
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PMID:Ibandronate, an experimental intravenous bisphosphonate for osteoporosis, bone metastases, and hypercalcemia of malignancy. 1663 95

Bisphosphonates are the most effective agents for treating and/or preventing complications of bone metastases and are the standard of care in this setting. Currently, four bisphosphonates are available for metastatic bone disease (MBD): clodronate, pamidronate, zoledronic acid, and ibandronate. Although all four of these bisphosphonates have been shown to reduce the incidence of skeletal-related events in patients with bone metastases, there are substantial differences among these agents in their potency, dose and route of administration, and side effects. Ibandronate and zoledronic acid, the two newer aminobisphosphonates, appear to have similar biochemical efficacies when phase III trial data are compared. Both agents were equally effective in reducing markers of bone resorption in the only prospective comparative trial carried out to date, but no data on relative clinical efficacy are available from head-to-head comparisons. Both the oral and i.v. formulations of ibandronate have also shown long-term efficacy in managing metastatic bone pain (MBP), but the onset of action of standard bisphosphonate treatment is not sufficient when rapid relief of pain is required. Because of its favorable renal safety profile, i.v. ibandronate can be administered daily for 3 days, as a so-called "loading dose." This dosing regimen has allowed rapid and effective relief of MBP without the unwanted side effects associated with opioids and other analgesics. Ibandronate is thus an effective, flexible, and well-tolerated bisphosphonate that can meet the varying requirements of patients with MBD.
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PMID:Ibandronate: its role in metastatic breast cancer. 1697 37

The anti-inflammatory and analgesic properties of different bisphosphonates have been demonstrated in both animal and human studies. Ibandronate is a third-generation bisphosphonate effective in managing different types of bone pain. In this study we investigated its effects in a standard pre-clinical model of inflammatory pain. We evaluated the effects of a single injection of different doses (0.5, 1.0, and 2.0 mg/kg i.p.) of ibandronate on inflammatory oedema and cutaneous hyperalgesia produced by the intraplantar injection of complete Freund's adjuvant (CFA) in the rat hind-paw. In addition, we measured the effects of this drug (1.0 mg/kg i.p.) on hind-paw levels of different pro-inflammatory mediators (PGE-2, SP, TNF-alpha, and IL-1beta). We also measured the levels of SP protein and of its mRNA in the ipsilateral dorsal root ganglia (DRG). Ibandronate proved able to reduce the inflammatory oedema, the hyperalgesia to mechanical stimulation, and the levels of SP in the inflamed tissue as measured 3 and 7 days following CFA-injection. This drug significantly reduced the levels of TNF-alpha and IL-1beta only on day 7. On the other hand, the levels of PGE-2 in the inflamed hind-paw were unaffected by the administration of this bisphosphonate. Finally, ibandronate blocked the overexpression of SP mRNA in DRG induced by CFA-injection in the hind-paw. These data help to complete the pharmacodynamic profile of ibandronate, while also suggesting an involvement of several inflammatory mediators, with special reference to substance P, in the analgesic action of this bisphosphonate.
Eur J Pain 2008 Apr
PMID:Effects of the bisphosphonate ibandronate on hyperalgesia, substance P, and cytokine levels in a rat model of persistent inflammatory pain. 1766 76

Several disorders of increased bone turnover and low bone mineral density (BMD) are associated with severe pain that is refractory to treatment with conventional and even opioid analgesics. Because of their ability to effectively improve the underlying pathogenesis of these disorders (i.e., reduce bone resorption and increase BMD), bisphosphonates are considered part of the palliative care of malignant bone-related pain and also appear to have some analgesic efficacy in other, non-malignant conditions. Ibandronate, a potent, nitrogen-containing bisphosphonate that can be given orally and intravenously, has demonstrated robust effects in relieving the pain associated with several malignant disorders. Unlike other available intravenous (i.v.) bisphosphonates, i.v. ibandronate is not associated with renal side effects, even at high doses such as 6 mg every 3 weeks. In addition, oral ibandronate (50 mg daily) is currently the only oral bisphosphonate proven to reduce and maintain bone pain scores below baseline for 2 years in patients with metastatic bone disease. Lower dose, less intense dosing regimens of ibandronate relieve bone pain in non-malignant conditions: i.v. ibandronate (2 mg every 3 months with or without an initial 4 mg injection) provides pain relief for patients with corticosteroid-induced osteoporosis, localised transient osteoporosis (bone marrow oedema) and sternocostoclavicular hyperostosis. Both oral and i.v. ibandronate are well tolerated. In conclusion, ibandronate offers an effective and convenient choice for the relief of bone pain in a wide variety of underlying bone conditions.
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PMID:A review of bone pain relief with ibandronate and other bisphosphonates in disorders of increased bone turnover. 1807 31


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