Approaches to managing bone metastases from breast cancer: the role of bisphosphonates.
TL;DR: Clinical trials are investigating additional indications for bisphosphonates, including the use of intensive dosing regimens for the relief of severe or opioid-resistant metastatic bone pain and adjuvant treatment for the prevention of bone metastases and cancer treatment-induced bone loss.
About: This article is published in Cancer Treatment Reviews.The article was published on 2005-06-01. It has received 20 citations till now. The article focuses on the topics: Bone pain & Bone disease.
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TL;DR: It is clearly demonstrate that osteoclasts stimulate angiogenesis in vivo through MMP-9, an angiogenic factor predominantly produced by osteoclast in bone, which is modulates osteoclast-stimulatedAngiogenesis primarily by affecting osteoclAST, most probably by previously reported migratory effects on osteoclasting.
171 citations
Cites background from "Approaches to managing bone metasta..."
...[181] N-BPs are also effective in myeloma bone disease....
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TL;DR: Approximate 40% of patients receiving aminobisphosphonates experience an acute phase response, which generally occurs only on first exposure to the drug and typically last <72 h.
Abstract: Background: Bisphosphonates are synthetic analogs of inorganic pyrophosphates with high avidity for bone, where they bind to hydroxyapatite crystals. Bisphosphonates are effective in decreasing bone resorption, the incidence of skeletal-related events, and pain from bone metastases. These agents have recently become incorporated into the treatment regimen of patients with osteolytic and osteoblastic metastatic bone disease. Although relatively well tolerated, the initial dose(s) of intravenous aminobisphosphonates can be associated with an acute phase response, a nonspecific physiologic reaction associated with increased levels of inflammatory cytokines, fever, and flu like symptoms including fatigue, nausea, and myalgia.Objective: The purpose of this article is to provide an updated review of the literature in this field.Data Sources: A search of PubMed was performed using the key terms bisphosphonate, acute phase response, and cancer, and limited to publications in English. The published literature on a...
75 citations
TL;DR: Combined radiotherapy and ibandronate provided substantial bone pain relief and increased bone density in patients with bone metastases from various solid tumors in this pilot study.
Abstract: Purpose: Ibandronate is a single-nitrogen, noncyclic bisphosphonate with proven efficacy for reducing metastatic bone pain. In this study, we assessed the palliative effects of combined ibandronate and radiotherapy. Methods and Materials: Forty-five patients with bone metastases from various solid tumors received externalbeam radiotherapy, 30‐40 Gy over 3‐4.5, weeks combined with 10 cycles of monthly intravenous ibandronate, 6 mg. Results: After combined therapy, mean bone pain scores (graded from 0 to 10) were reduced from 6.3 at baseline to 0.8 after 3 months, with further reductions at later time points (all p < 0.001). Opioid use decreased from 84% of patients at baseline (38/45) to 24% (11/45) at 3 months, with further subsequent reductions (all p < 0.001). Mean performance status and functioning scores also significantly improved. Bone density (assessed by computed tomography scan) increased by 20% vs. baseline at 3 months, 46% at 6 months, and 73% at 10 months (all p < 0.001). Lesion improvement was also demonstrated by magnetic resonance imaging. Treatment was well tolerated with no renal toxicity. Conclusions: In this pilot study, combined radiotherapy and ibandronate provided substantial bone pain relief and increased bone density. Computed tomography-based or magnetic resonance imaging‐based evaluations offer objective methods for assessing therapeutic outcomes. © 2007 Elsevier Inc. Bisphosphonate, Bone metastases, Ibandronate, Radiotherapy, Bone density.
64 citations
Journal Article•
TL;DR: Evaluation of the therapeutic effects of (186)Re-MAG3-HBP using an animal model of bone metastasis indicates that it could be useful as a therapeutic agent for the palliation of metastatic bone pain.
Abstract: this study, we evaluated the therapeutic effects of 186Re-MAG3HBP using an animal model of bone metastasis. Methods: The model was prepared by injecting syngeneic MRMT-1 mammary tumor cells into the left tibia of female Sprague–Dawley rats. 186Re-MAG3-HBP (55.5, 111, or 222 MBq/kg) or 186Re-HEDP (55.5 MBq/kg) was then administered intravenously 21 d later. To evaluate the therapeutic effects and side effects, tumor size and peripheral blood cell counts were determined. Palliation of bone pain was evaluated by a von Frey filament test. Results: In the rats treated with 186 Re-HEDP, tumor growth was comparable with that in untreated rats. In contrast, when 186 Re-MAG3-HBP was administered, tumor growth was significantly inhibited. Allodynia induced by bone metastasis was attenuated by treatment with 186Re-MAG3-HBP or 186Re-HEDP, but 186Re-MAG3-HBP tended to be more effective. Conclusion: These results indicate that 186Re-MAG3-HBP could be useful as a therapeutic agent for
42 citations
Cites background from "Approaches to managing bone metasta..."
...Bisphosphonates have been used primarily to treat hypercalcemia (from excess bone resorption) and, more recently, cancer-induced bone pain (32)....
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...Recent reports indicate that the regular use of bisphosphonates for metastatic bone disease prevents skeletal-related events, reduces bone pain, and improves the patient’s quality of life (32,33)....
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TL;DR: The feasibility of the hypothesis that the osteoclast can be a proangiogenic cell is discussed, and reasons supporting the feasibility of this hypothesis include proang iogenic factors produced by osteoclasts, the angiogenic effects of macrophages, the antiangiogenesis effects of nitrogen containing bisphosphonates, and the physical proximity of osteoclast to endothelial cells.
Abstract: There have been reports recently that the osteoclast stimulates angiogenesis in vitro. We review the evidence suggesting that the osteoclast directly stimulates angiogenesis, and discuss the feasibility of the hypothesis that the osteoclast can be a proangiogenic cell. Reasons supporting the feasibility of this hypothesis include proangiogenic factors produced by osteoclasts, the angiogenic effects of macrophages, the antiangiogenic effects of nitrogen containing bisphosphonates, and the physical proximity of osteoclasts to endothelial cells.
19 citations
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2,629 citations
TL;DR: The most common human cancers — lung, breast and prostate — have a great avidity for bone, leading to painful and untreatable consequences.
Abstract: The most common human cancers --lung, breast and prostate -- have a great avidity for bone, leading to painful and untreatable consequences. What makes some cancers, but not others, metastasize to bone, and how do they alter its physiology? Some of the molecular mechanisms that are responsible have recently been identified, and provide new molecular targets for drug development.
2,367 citations
TL;DR: In view of the current trend of increasing and widespread use of chronic bisphosphonate therapy, the observation of an associated risk of osteonecrosis of the jaw should alert practitioners to monitor for this previously unrecognized potential complication.
1,964 citations
TL;DR: Ongoing research is aimed at trying to define the optimum route, dose, schedule and type of bisphosphonate in metastatic bone disease and in the prevention and treatment of osteoporosis in cancer patients.
1,683 citations
TL;DR: In this paper, pamidronate disodium (90 mg) was given to women with stage IV breast cancer who were receiving cytotoxic chemotherapy and had at least one lytic bone lesion.
Abstract: Background Bisphosphonates such as pamidronate disodium inhibit osteoclast-induced bone resorption associated with cancer that has metastasized to bone. Methods Women with stage IV breast cancer who were receiving cytotoxic chemotherapy and had at least one lytic bone lesion were given either placebo or pamidronate (90 mg) as a two-hour intravenous infusion monthly for 12 cycles. Skeletal complications, including pathologic fractures, the need for radiation to bone or bone surgery, spinal cord compression, and hypercalcemia (a serum calcium concentration above 12 mg per deciliter [3.0 mmol per liter] or elevated to any degree and requiring treatment), were assessed monthly. Bone pain, use of analgesic drugs, performance status, and quality of life were assessed throughout the trial. Results The efficacy of treatment was evaluated in 380 of 382 randomized patients, 185 receiving pamidronate and 195 receiving placebo. The median time to the occurrence of the first skeletal complication was greater in the pa...
1,008 citations