Mineralization bone synthesis

Insufficient intakes of Mn and Cu resulted in significant abnormalities in both serum and bone mineral levels within twelve months. Why a chronic deficiency of trace elements should result in conditions of osteopenia is not at present clear. It has been suggested that osteopenia is associated with an increased rate of bone resorption (33). Others have implicated decreased bone formation or osteoblast activity in some forms of osteoporosis (34). What is obviously at issue is a balance between the rate of bone resorption and that of bone synthesis (35-37). Bow that equilibrium dynamic is affected by trace elements will be discussed below. 

Gonzalez KA, Wilson LJ, Wu W, Nancollas GH. Synthesis and in vitro characterization of a tissue-selective fullerene vectoring C(60)(OH)(16)AMBP to mineralized bone. Bioorg Med Chem 2002 10 1991-7. 

Biosynthesis and degradation of glycosaminoglycans biosynthesis of collagen, mineralization and demineralization of bone. Fatty acid synthesis and triglyceride storage in adipocytes promoted by insulin and triglyceride hydrolysis and fatty acid release stimulated by glucagon and adrenaline (epinephrine). 

Many of the adverse effects of lithium can be ascribed to the action of lithium on adenylate cyclase, the key enz)nne that links many hormones and neurotransmitters with their intracellular actions. Thus antidiuretic hormone and thyroid-stimulating-hormone-sensitive adenylate cyclases are inhibited by therapeutic concentrations of the drug, which frequently leads to enhanced diuresis, h)rpoth)n oidism and even goitre. Aldosterone synthesis is increased following chronic lithium treatment and is probably a secondary consequence of the enhanced diuresis caused by the inhibition of antidiuretic-hormone-sensitive adenylate cyclase in the kidney. There is also evidence that chronic lithium treatment causes an increase in serum parathyroid hormone levels and, with this, a rise in calcium and magnesium concentrations. A decrease in plasma phosphate and in bone mineralization can also be attributed to the effects of the drug on parathyroid activity. Whether these changes are of any clinical consequence is unclear. 

Mechanism of Action A polypeptide hormone that stimulates cartilaginous growth areas of long bones, increases the number and size of skeletal muscle cells, influences the size of organs, and increases RBC mass by stimulating erythropoietin. Influences the metabolism of carbohydrates (decreases insulin sensitivity), fats (mobilizes fatty acids), minerals (retains phosphorus, sodium, potassium by promotion of cell growth), and proteins (increases protein synthesis). Therapeutic Effect Stimulates growth. 

The mechanism of action of the vitamin D metabolites remains under active investigation. 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 TRPV6, an intestinal calcium channel) 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... 

Plicamycin is a cytotoxic antibiotic (see Chapter 54) that has been used clinically for two disorders of bone mineral metabolism Paget s disease and hypercalcemia. The cytotoxic properties of the drug appear to involve its binding to DNA and interruption of DNA directed RNA synthesis. The reasons for its usefulness in the treatment of Paget s disease and hypercalcemia are unclear but may relate to the need for protein synthesis to sustain bone resorption. The doses required to treat Paget s disease and hypercalcemia are about one tenth the amounts required to achieve cytotoxic effects. 

The effects of vitamin D metabolites on bone itself are somewhat unclear. Some metabolites seem to promote bone resorption and others seem to favor bone formation.10 The overall influence of vitamin D, however, is to enhance bone formation by increasing the supply of the two primary minerals needed for bone formation (calcium and phosphate). Vitamin D also directly suppresses the synthesis and release of PTH from the parathyroid glands, an effect that tends to promote bone mineralization by limiting the catabolic effects of PTH.46,92... 

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