Bone remodeling calcitonin

Calcitonin is used in the treatment of Paget s disease (osteitis deformans), a chronic disorder characterized by increased bone remodeling, normocalcemia and normophosphatemia, frequent episodes of hypercalciuria leading to stone formation, and elevation of serum alkaline phosphatase and urinary hydroxyproline levels. The disease does not appear to be primarily a derangement of calcium metabolism. Calcitonin reduces the levels of serum alkaline phosphatase and urinary hydroxyproline, and may relieve other symptoms of the disease as well. Diphosphonates, especially etidronate disodium, also reduce bone resorption in this disease. Various cancers are accompanied by hypercalcemia and may respond to treatment with calcitonin. 

Disorders of bone Bisphosphonates, calcitonin, estrogen, calcitonin, remodeling calcium, fluoride, PTH + vitamin D... 

Prevention of osteoporosis and fracture can be achieved through limiting the resorption-remodeling process. Four main families of products can be effective in controlling bone resorption estrogens, SERMs, bisphosphonates, and calcitonin. Large, prospective randomized trials have proven the effectiveness... 

The calcium taken up by living systems will be found mainly as extracellular deposits or structures, with a small amount present in intracellular stores, together with some in various extracellular fluids. The calcium in fluids will be bound to protein or will be free in solution, with a few percent bound to small molecules or anions. The calcium in solution will exchange with the calcium in structures such as bone and teeth, due to the activity of hormones such as l,25-(OH)2D3, parathyroid hormone and calcitonin,455 which are responsible for the remodelling and repair of bone. 

Paget disease Excessive bone formation and resorption (turnover] leads to ineffective remodeling and structural abnormalities within the bone Calcitonin, bisphosphonates... 

Bisphosphonates concentrate at sites of active remodeling. Because they are highly negatively charged, bisphosphonates are membrane impermeable but are incorporated into the bone matrix by huid-phase endocytosis. Bisphosphonates remain in the matrix until the bone is remodeled and then are released in the acid environment of the resorption lacunae beneath the osteoclast as the overlying mineral matrix is dissolved. The importance of this process for the antiresorp-tive effect of bisphosphonates is evidenced by the fact that calcitonin blocks the antiresorptive action. 

Much evidence exists to support the contention that boron has beneficial effects on bone. The effects of boron, however, are most evident in the presence of suboptimal status of another nutrient important in bone formation or remodeling. In chicks, boron deprivation (0.465 mgkg diet) exacerbates the distortion of marrow sprouts (location of calcified scaffold erosion and new bone formation) and delay in imtiation of cartilage calcification in bones during marginal vitamin D deficiency (Hunt 1996). In humans, estrogen therapy to maintain bones increases serum 17P-estra-diol this increase is depressed when dietary boron intake is low (0.25-0.35 g per day) (Nielsen 1996, 1997). Boron deprivation also can exacerbate the increase in serum calcitonin and osteocalcin caused by low dietary copper and magnesium in humans. 

Calcitonin therapy requires the concomitant oral administration of elemental calcium (500 mg/day). Clinical studies have shown that the combination of intranasal calcitonin salmon (200 lU/day), oral calcium supplementation (>1,000 mg/day of elemental calcium), and vitamin D (400 lU/day) has decreased the rate of new fractures by more than 75% and has improved vertebral BMD by as much as 3% annually (3). Calcitonin prevents the abnormal bone turnover characteristic of Paget s disease of the bone and has antiresorptive activity. In the presence of calcitonin, the osteoclast brush borders disappear, and the osteoclasts move away from the bone surface undergoing remodeling (36). Side effects are significantly more pronounced when calcitonin-salmon Is administered by injection and can include nausea, vomiting, anorexia, and flushing. Because calcitonin-salmon Is protein in nature, the possibility of a systemic allergic reaction should be considered. 

A more positive control of calcium ion concentration is brought about by the cell-mediated resorption or deposition of stable bone material. These adjustments are slower, but quantitatively greater, than the simple exchange reaction. They take place with great precision with regard to the sites in the bone where resorption and deposition occur, their timing and the constancy of plasma ion concentration achieved. The process thus provides for both the continuous remodelling of bone and for the calcium-phosphorus homoeostasis of the blood and tissue fluids. The former depends on the position on the bone surface of various stimulated cells and the latter on the net result of stimulation of cells in bone, intestine and kidney by parathyroid hormone, calcitonin and vitamin D. The mode of action of these substances and the interplay of their various effects are complex. 

The antagonistic effects of calcitonin on bone resorption also appear to require the presence of vitamin D. Thus the vitamin is necessary for the action of both PTH, which promotes resorption, and calcitonin, which inhibits it. This is just one more aspect of the complex interplay of mechanisms involving these three substances which ensure the stability of blood calcium and the proper maintenance of the calcified tissues through continuous remodelling. 

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