Bone-specific agent

Strontium ranelate is an orally active agent that can be classified as both an antiresorptive agent and a bone-forming agent (42,43). It is able not only to stimulate replication of preosteoblastic cells to promote bone formation but also is able to decrease osteoclastic activity to prevent bone resorption. Biochemical markers for bone formation (e g., bone-specific alkaline phosphatase), which normally decrease in the presence of antiresorptive therapy, are elevated in the presence of strontium ranelate (44). Lumbar spine BMD increased 11.4% in patients treated with this new agent. 

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

Ifosfamide -alkylating agent noncell cycle specific -bone marrow suppression -hemorrhagic cystitis (need Mesna uroprotection) -nausea and vomiting—mild to moderate -mucocutaneous effects (mucositis, stomatitis, diarrhea) -CNS toxicity—lethargy, stupor, coma, seizures... 

CSF levels in normal human serum are usually low or undetectable. During infections, the immune system responds by activation of leukocytes, and often this is accompanied by an increase in numbers of specific leukocytes in the circulation in order to combat the infective agent. Thus, it is not surprising that many pathogens activate CSF production, which then results in increases in numbers of progenitor cells in the bone marrow and spleen, and subsequent increases in numbers of mature leukocytes in the circulation. 

Another group of blood tests involves bacteriological techniques. Blood and bone marrow samples are obtained under aseptic precautions and introduced into a variety of artificial culture media, with subsequent isolation and identification of the specific microorganism responsible for the illness. Relative susceptibility of the specific strain of bacteria to the available chemotherapeutic and antibiotic agents may then be determined and the effectiveness of such agents in sterilizing the blood-stream can be determined by further blood cultures. 

Pharmacological and toxicological studies have shown that demetallation can occur in vivo with deposition of free metal ions in bone and liver especially in situations where the chelate has a long residence time in the body. This is the case with non-extracellular chelates like organ-specific contrast agents or with intravascular compounds such as polymers. 

However, calcitriol is well established as the most potent agent with respect to stimulation of intestinal calcium and phosphate transport and bone resorption. Calcitriol appears to act on the intestine both by induction of new protein synthesis (eg, calcium-binding protein) and by modulation of calcium flux across the brush border and basolateral membranes by a means that does not require new protein synthesis. The molecular action of calcitriol on bone has received less attention. However, like PTH, calcitriol can induce RANK ligand in osteoblasts and proteins such as osteocalcin, which may regulate the mineralization process. The metabolites 25(OH)D and 24,25(OH)2D are far less potent stimulators of intestinal calcium and phosphate transport or bone resorption. However, 25(OH)D appears to be more potent than l,25(OH)2D in stimulating renal reabsorption of calcium and phosphate and may be the major metabolite regulating calcium flux and contractility in muscle. Specific receptors for l,25(OH)2D exist in target tissues. However, the role and even the existence of receptors for 25(OH)D and 24,25(OH)2D remain controversial. 

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