Metastatic bone disease

This yields 89Sr in low specific activity however, this is sufficient for use as a pain palliation agent in metastatic bone disease. 

The thermal neutron production product, 153Sm, is used in the formulation of Quadramet , a US FDA-approved radiopharmaceutical for pain palliation in metastatic bone disease. It is produced by an (n, 7) reaction on 152Sm ... 

Sr, as the strontium ion (Sr2+), is used for pain palliation in patients with metastatic bone disease. The strontium ion is a calcium ion mimic, being taken up in metabolically active bone such as cancer. 89Sr is a therapeutic radionuclide with a half-life of 50.53 days, emitting a 1.49 MeV [3 particle on decay. Several recent reviews discuss the use of radionuclides and their complexes as pain palliation agents in metastatic bone disease.18,212-215... 

Metastatic bone disease (MBD) is characterized by very high levels of bone turnover in regions proximal to the tumour [33]. Bone resorption inhibitors such as bisphosphonates represent the current standard of care for the treatment of bone metastases primarily due to breast or prostate cancer and multiple myeloma. It has been proposed that other strong anti-resorptives such as a Cat K inhibitor could be useful in the treatment of bone metastases. Evidence for this has been presented in the form of a preclinical MBD model in which human breast cancer cells are implanted into nude mice. Treatment with a Cat K inhibitor gave a significantly lower area of breast cancer-mediated osteolytic lesions in the tibia [34]. In a separate study, the efficacy of a Cat K inhibitor in the reduction in tumour-induced osteolysis was found to be enhanced in the presence of the bisphosphonate zolendronic acid [35,36]. When prostate cancer cells were injected into the tibia of SCID mice, treatment with a Cat K inhibitor both prevented and diminished the progression of cancer growth in bone [37]. 

Fleisch H. Bisphosphonates—pharmacology and use in the treatment of tumor-induced hypercalcemic and metastatic bone-disease. Drugs 1991 42 919-944. 

While no in vivo activity has been reported in an Abl-dependent CML model, AZD0530 was active in a xenograft model using Src-transformed NIH 3T3 cells and in an orthotopic model of pancreatic cancer, two Src-dependent models. The results of a Phase I trial in normal volunteers have been disclosed and AZD0530 was tolerated when administered at doses of up to 250 mg [156,157]. While it appears that the initial efficacy trial for AZD0530 will be as an anti-invasive agent for the treatment of metastatic bone disease, this compound probably also has potential for use in CML. 

Kanakis I, Kousidou OCh, Karamanos NK. In vitro and in vivo antiresorptive effects of bisphosphonates in metastatic bone disease. In Vivo. 2005 19 311-318. 

Osteolytic tumors may induce bone destruction either through local invasion, or by a secondary metastatic bone disease. The most frequent types of primary tumors that develop into metastatic bone disease are, in the order of prevalence breast, prostate, thyroid, kidney, and bronchial tumors, whereas esophageal, gastrointestinal and rectal tumors are much less metastatic [11]. Very often, the destruction of bone in a metastatic bone disease leads to hypercalcemia of malignancy, which also responds to BPs. In addition, hematological cancers such as... 

Bone metastasis is one of the most frequent causes of pain in patients with cancer. Bone is a common site for circulating cancer cells to settle and grow, either near or far from the primary tumour site. Metastatic bone disease is not the same as primary bone cancer. 

Oral ibandronate has also been investigated in patients with metastatic bone disease. In 2 pooled Phase III studies, 564 patients with metastatic bone disease from breast cancer were randomised to receive 50 mg oral ibandronate or placebo once daily for up to 96 weeks [84]. Oral ibandronate significantly reduced the mean rate of new skeletal complications by almost 20% compared with placebo (P=0.004). The incidence of mild treatment-related upper gastrointestinal adverse events was slightly higher for oral ibandronate compared with the placebo group, whereas the renal adverse event rate was comparable between the 2 groups (ibandronate, 5.2% placebo, 4.7%) with no report of renal failure [84]. 

Berenson JR, Vescio R, Flenick K, Nishikubo C, Rettig M, Swift RA, Conde F, VonTeichert JM. A phase I, open label, dose ranging trial of intravenous bolus zoledronic acid, a novel bisphosphonate, in cancer patients with metastatic bone disease. Cancer 2001 91 144-154. 

Diel I, BodyJJ, Bergstrom B. Renal safety of intravenous (i.v.) ibandronatefor up to 4years of treatment in patients with metastatic bone disease [abstract]. Ann Oncol 2004 15(suppl 3) iii224. Abstract 850P. 

Mancini I, Dumon JC, BodyJJ. Efficacy and safety of ibandronate in the treatment of opioid-resistant bone pain associated with metastatic bone disease a pilot study. J Clin Oncol 2004 22 3587-3592. 

Pecherstorfer M, Diel IJ. Rapid administration of ibandronate does not affect renal functioning evidence from clinical studies in metastatic bone disease and hypercalcaemia of malignancy. Support Care Cancer 2004 12 877-881. 

Body JJ, Diel IJ, Lichinitzer M, Lazarev A, Pecherstorfer M, Bell R, Tripathy D, Bergstrom B. Oral ibandronate reduces the risk of skeletal complications in breast cancer patients with metastatic bone disease results from two randomised, placebo-controlled phase III studies. Br J Cancer 2004 90 1133-1137. 

In addition to their use m metabohc bone disease, markers of bone turnover are potentially useful tools in diagnosing and monitoring metastatic bone disease. As with metabolic bone disease, there is more evidence supporting the use of resorption markers m monitoring therapy. Additional studies are required to determine the ultimate clinical utility of bone markers in metastatic bone disease. 

Elevated concentrations of telopeptides and DPD have been reported in osteoporosis, Paget s disease, metastatic bone disease, primary and secondary hyperparathyroidism, hyperthyroidism, and other diseases with increased bone... 

Fohr B, Dunstan CR, Seibel MJ. Markers of bone remodeling in metastatic bone disease. J Clin Endocrinol Metab 2003 88 5059-75. 

Diener, K.M. Bisphosphonates for controlling pain from metastatic bone disease. Am. J. Health-Syst. Pharm. 1996, 53, 1917-1927, (Aug. 15). 

R5. Raskin, P., McClain, C. J., and Medsger, T. A., Hypocalcemia associated with metastatic bone disease. Arch, Intern. Med. 132, 539-543 (1973). 

Bone metastases are common in many advanced cancers and are a clinically relevant source of skeletal morbidity. Nearly 30% of all malignant tumors induce bone metastases Qemal et al. 2004 Thomas et al. 1996). Most often, the spinal column (80%) and the femur (40%) are affected. In particular, breast, lung and bronchus, prostate and kidney cancer types have a high rate of inducing bone metastases. Prostate cancer in males and breast cancer in females are the most common cancer types (Jemal et al. 2004). In the US 33% of the estimated new cases of cancer in males are induced by prostate cancer (230,110 cases of new prostate cancer per year). Of the new cases in females, 32% are induced by breast cancer (215,990 cases of new breast cancer per year) (Jemal et al. 2004 Thomas et al. 1996). Of all patients with breast and prostate cancer, 60%-80% develop bone metastases. Pain is the most frequent complication in metastatic bone disease. More than 80% of patients suffer from pain with a reduction of mobility and life quality therefore they have a high risk of concomitant complications. Therapy of bone metastases has three main goals ... 

Tuncay 1C, Condrad EU (1993) Metastatic bone disease. J Arthroplasty Arthrosc Surg 7 80-8218... 

Mineral balance Denosumab which targets RANKL, receptor activator of nuclear factor kappa-B ligand (CD254), a member of the TNF cytokine family, is approved for bone metastases and osteoporosis. It is well known that denosumab can cause hypocalcaemia and bone loss but the incidence of hypocalcaemia caused by this mAb may be higher than previously reported and while hypocalcaemia is usually asymptomatic and transient, cardiac arrhythmias and death are possible serious outcomes [133 ]. Despite calcium and vitamin D supplementation, denosumab-treated patients with high bone turnover from metastatic bone disease or secondary hyperparathyroidism due to renal failure should be closely monitored, especially for serum calcium levels 8-14 days post denosumab [133 ]. 

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