Hyperparathyroidism Bone resorption

Hyperparathyroidism Excess parathormone causes bone resorption. 

Glucocorticoids decrease bone formation through decreased proliferation and differentiation, and enhanced apoptosis of osteoblasts. They also increase bone resorption, decrease calcium absorption, increase renal calcium excretion, and result in secondary hyperparathyroidism. 

Cancer and hyperparathyroidism are the most common causes of hypercalcemia. The primary mechanisms are increased bone resorption, increased GI absorption, and decreased renal elimination. 

High phosphate diets cause decreased Ca absorption, secondary hyperparathyroidism, accelerated bone resorption and soft tissue calcification in some animals, but not in normal humans. Although phosphates may decrease Ca absorption in man at very high (> 2000 mg/day) Ca intakes, they do not do so at more moderate Ca levels and enhance Ca absorption at very low levels (< 500 mg/day). Phosphates increase renal tubular reabsorption and net retention of Ca. At low Ca intakes, phosphates stimulate parathyroid hormone (PTH) secretion without causing net bone resorption. 

The major location of calcium in the body is in the skeleton, which contains more than 90% of the body calcium as phosphate and carbonate. Bone resorption and formation keeps this calcium in dynamic equilibrium with ionized and complexed calcium in blood, cellular fluids and membranes. Homeostasis is mainly regulated by the parathyroid hormone and vitamin D which lead to increased blood calcium levels, and by a thyroid hormone, calcitonin, which controls the plasma calcium concentration J5 Increasing the concentration of calcitonin decreases the blood calcium level, hence injections of calcitonin are used to treat severe hyperalcaemia arising from hyperparathyroidism, vitamin D intoxication or the injection of too high a level of parathyroid extract. High levels of calcitonin also decrease resorption of calcium from bone. Hypocalcaemia stimulates parathyroid activity, leading to increased release of calcium from bone, reduction in urinary excretion of calcium and increased absorption of calcium from the intestine. Urinary excretion of phosphate is enhanced. 

Calcitonin is a peptide hormone produced in the thyroid gland that serves to lower serum calcium and phosphate levels by inhibiting bone resorption. Calcitonin has been used in the treatment of a variety of diseases, such as primary hyperparathyroidism, Paget s disease, and postmenopausal osteoporosis [99,100]. Salmon calcitonin has a longer half-life than human calcitonin. Salmon calcitonin, 3.6 kDa, is available as a nasal formulation that contains only benzalkonium chloride as a preservative, without an absorption enhancer, and as a parenteral product for injection. The direct effect of benzalkonium chloride on the nasal mucosa is under... 

Hyperparathyroidism Increased parathyroid hormone secretion, usually caused by parathyroid tumors leads to excessive bone resorption and hypercalcemia Usually treated surgically by partial or complete resection of the parathyroid gland... 

The polypeptide parathormone is released from the parathyroid glands when the plasma Ca2+ level falls. It stimulates osteoclasts to increase bone resorption in the kidneys it promotes calcium reabsorption, while phosphate excretion is enhanced. As blood phosphate concentration diminishes, the tendency of Ca2+ to precipitate as bone mineral decreases. By stimulating the formation of vitamin D hormone, parathormone has an indirect effect on the enteral uptake of Ca2+ and phosphate. In parathormone deficiency, vitamin D can be used as a substitute that, unlike parathormone, is effective orally. Teriparatide is a recombinant shortened parathormone derivative containing the portion required for binding to the receptor. It can be used in the therapy of postmenopausal osteoporosis and promotes bone formation. While this effect seems paradoxical in comparison with hyperparathyroidism, it obviously arises from the special mode of administration the once daily s.c. injection generates a quasi-pulsatile stimulation. Additionally, adequate intake of calcium and vitamin D must be ensured. 

OH)2D3 concentrations. Low l,25-(OH)2D3 results in little to no intestinal calcium absorption for soft tissue needs. Thus, blood calcium can be low and secondary hyperparathyroidism develops. The inability to regulate renal handling of phosphate by PTH leads to phosphate-mediated repression of ionized calcium. Serious osteodystrophic lesions occur because of high PTH activity on bone resorption resulting in osteitis fibrosa and osteosclerosis. 

Q9 The hypercalcaemia which occurs in hyperparathyroidism may be reduced by administration of a loop diuretic such as furosemide, which helps calcium excretion. Bisphosphonates, which prevent bone resorption and so reduce calcium release from bone, can be used to treat hypercalcaemia associated with malignancies. Calcitonin may also be useful in treating the hypercalcaemia associated with cancer, as it reduces calcium levels both by attenuating its renal reabsorption and by increasing calcium deposition in bone. 

Of 19 chronic hemodialysis patients taking a combination of alfacalcidol and calcitriol for 12 months, six had increased bone resorption, six had reduced bone resorption, and seven had no change. Histologically documented aggravation of hyperparathyroidism was associated with a statistically significant increase in plasma concentrations of phosphate and parathyroid hormone. The administration of vitamin D analogues may therefore be either beneficial or noxious depending on whether or not induced hyperphosphatemia is adequately prevented (55). 

Hypercalcemia occurs in 10% to 20% of individuals with cancer. Tumors most commonly cause hypercalcemia by producing PTHrP, which is secreted into the circulation and stimulates bone resorptions and/or by invasion of the bone by metastatic tumor, which produces local factors that stimulate bone resorption. PTHrP binds to the PTH receptor and is the principal mediator of humoral hypercalcemia of malignancy (HHM). Cytokines such as lymphotoxin, interleukin-1, tumor necrosis factor, and PTHrP appear to be important mediators of hypercalcemia in multiple myeloma and other hematological malignancies. Some lymphomas associated with acquired immunodeficiency syndrome or HTLV [ infections cause hypercalcemia by producing 1,25(0H)2D. It is estimated that 5% of patients with hypercalcemic cancer have coexisting primary hyperparathyroidism. 

Vitamin D is responsible for maintaining calcium homeostasis. Low calcium concentrations lead to hyperparathyroidism and bone resorption. Vitamin D insufficiency (11 to 20 ng/mL) and deficiency (<10 ng/mL) [25(OH) vitamin D measurement, 10 ng/mL = 25 mcmol/L] is becoming more commonly recognized in all age groups, ° especially malnourished individuals, northerners, women wearing veiled dresses, African-Americans, seniors, and long-term care residents. Low vitamin D concentrations resnlt from insufficient intake, decreased sun exposure, decreased skin production, decreased liver and renal metabolism, and winter residence in northern climates. 

The bone resorption is responsible for a high alkaline phosphatase level in the serum. The activity of the alkaline phosphatase in the serum can be correlated with the degree of bone demineralization. Of course, alkaline phosphatase is of diagnostic value only if diseases of the hepatic system have been ruled out. The serum inorganic phosphorus levels are reduced in hyperparathyroidism. 

Mineral balance. Hypocalcaemia Treatments that inhibit osteoclast bone resorption might induce hypocalcaemia and secondary hyperparathyroidism. Both situations can be attenuated by previous administration of vitamin D. Symptomatic hypocalcaemia, however, is usually uncommon with oral bisphosphonate. 

Renal osteodystrophy is a complex disorder with several pathogenic factors. Histological evidence of bone disease is common in early renal failure and deficits in calcitriol synthesis seems to be an important factor in the pathogenesis of secondary hyperparathyroidism in early CRF. The most common component is osteitis fibrosa manifested as subperiosteal resorption of bone. This is due to decreased excretion as well as increased secretion of parathyroid hormone. In CRF small increments of serum phosphorus cause small decreases in serum calcium. 

There can be increases in calcium and phosphorus loss because of effects on both the kidney and the bowel, with increased excretion and reduced resorption (131). Tetany, which has been seen in patients receiving high-dose longterm intravenous glucocorticoids, has been explained as being due to hypocalcemia, and there are also effects on bone. Tetany has also been reported in a patient with latent hyperparathyroidism after the administration of a glucocorticoid (122). 

Hypercalcemia is commonly encountered in clinical prac-results when the flux of calcium into the extracellular fluid compartment from the skeleton, intestine, or Iddney is greater than the efflux. For example, when excessive resorption of bone mineral occurs in malignancy, hy-percalciuria develops. When the capacity of the kidney to excrete filtered calcium is exceeded, hypercalcemia develops. Hypercalcemia can be caused by increased intestinal absorption (vitamin D intoxication), increased renal retention (thiazide diuretics), increased skeletal resorption (immobilization), or a combination of mechanisms (primary hyperparathyroidism). 

In patients with hypercalcemia, treatment with a loop diuretic plus saline promotes calcium excretion and helps lower serum calcium. In patients with intact regulatory function, increases in calcium resorption promoted by thiazides have minor impact on serum calcium due to buffering in bone and gut. However, thiazides can unmask hypercalcemia that occurs in diseases that disrupt normal calcium regulation (eg, hyperparathyroidism, sarcoidosis, carcinoma). 

The effect of parathyroid hormone upon bone is considered by Albright to be secondary to the increase in urinary phosphate excretion, the depletion of serum phosphate causing accelerated resorption of phosphate from bone which is inevitably accompanied by increased calcium resorption. This author distinguishes between hyperparathyroidism with bone disease and a like condition without bone disease. In the former there is an increase in the resorption of bone with a compensatory increase in bone formation, the osteoblasts and osteoclasts being numerically increased and the phosphatase activity of the serum raised. The latter condition shows normal bone metabolism, and the increased calcium excretion is postulated to come entirely from increased calcium intake and absorption, whereas serum phosphatase activity is normal. 

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