Bisphosphonates metastatic bone

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]. 

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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. 

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Bisphosphonates (see later). Pamidronate is infused according to the schedule in Table 38.1 it is active in a wide variety of hypercalcaemic disorders. Fall in serum calcium begins in 1-2 d, reaches a nadir in 5-6 d and lasts 20-30 d. Etidronate may be given i.v. in hypercalcaemia of malignant disease. It acts in 1-2 d and a dose lasts 3 weeks it may also provide benefit for neoplastic metastatic disease in bone. Clodronate (oral or i.v.) or zoledonic acid (i.v) are alternatives. 

Ninety percent of cancer deaths are caused by metastatic rather than primary tumors. Define metastasis. Explain the rationale for the following new cancer treatments (a) batima-stat, an inhibitor of matrix metalloproteinases and of the plasminogen activator receptor, (b) antibodies that block the function of integrins, integral membrane proteins that mediate attachment of cells to the basal laminae and extracellular matrices of various tissues, and (c) bisphosphonate, which inhibits the function of bone-digesting osteoclasts. 

Bisphosphonates (BPs) are compounds belonging to an important therapeutic class for bone disease treatment (Paget s disease, metastatic and osteolytic bone disease and osteoporosis). Since the beginning of their clinical use in the late 1960s, the... 

Most cases of bisphosphonate-related osteonecrosis occur after intravenous administration of bisphosphonate treatment for malignant bone disease and metastatic cancer. As the incidence of osteonecrosis caused by oral administration is low, it is believed that bisphosphonates are relatively safe and effective in preventing the complications of osteoporosis, such as hip or spine fractures. Osteonecrosis caused by oral bisphosphonates has been described in five Asian women aged over 65 years [15 ]. Three had also used glucocorticoids for rheumatoid arthritis. Irrespective of race, the elderly women undergoing glucocorticoid therapy have an increased incidence of osteonecrosis even with oral bisphosphonates. 

Aredia, pamidronate disodium (APD), is a bone-resorption inhibitor used to treat hypercalcemia associated with malignancy and osteolytic bone lesions associated with multiple myeloma, metastatic breast cancer, and moderate to severe Paget s disease of bone. Aredia, a member of the group of chemical compounds known as bisphosphonates, is an analog of pyrophosphate. Pamidronate disodium is designated chemically as phosphonic acid (3-amino-l-hydroxypropylidene) bis-, disodium salt, pentahydrate, (APD). 

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