Hyperparathyroidism Osteoclasts

The calcium value is only slightly raised hut the PTH concentration, although within the stated reference range, is inappropriately high for the stated calcium concentration. Normally, PTH and calcium concentrations are inversely related. A diagnosis of primary hyperparathyroidism was subsequently confirmed. The role of PTH is to raise plasma calcium concentration, partly, by enhancing osteoclast activity. 

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. 

Hypercalcemia occurs with hyperparathyroidism, a disease involving the excessive production of PTH by the parathyroid gland. Hypercalcemia can result from cancers that produce l,25-(OH)jDg, Cancer cells produce a variety of other molecules that stimulate osteoclasts this condition is called oncogenic hypercalcemia. 

Slight or moderate elevations in serum TR-ACP activity often occur in Paget s disease, in hyperparathyroidism with skeletal involvement, and in the presence of malignant invasion of the bones by cancers, such as breast cancer in women. Increased concentrations of the osteoclast-derived AGP are also present in serum in osteoclastoma (giant-cell tumor), an osteoclastic neoplasm, and in osteopetrosis (marble bone disease) in which the osteoclasts fail to resorb bone. High concentrations... 

The drug presently has its main carcinolytic indication in the treatment of testicular carcinoma. An unrelated effect, probably on osteoclast bone cells, leads to a significant reduction of plasma calcium at one-tenth the antineoplastic dose. This has been useful in hypercalcemia of malignancy, Paget s disease, and hyperparathyroid conditions. 

The typical bone disease caused by hyperparathyroidism is von Recklinghausen s disease of bone. The histopathogenesis of the bone disease can be classified as decalcification, loss of organic matrix, and fibrous proliferation. In those areas of the bone affected by the disease, the bone salts are lost first. Demineralization is followed by a loss of matrix substance and invasion of the area by osteoclasts. The proliferation of the osteoclast may be so considerable that it may lead to the formation of brown giant cell tumors. Fibrous tissue proliferates in the digested areas, and the new connective tissue may or may not become calcified. These areas of demineralization and fibrosis become susceptible to fracture, creating a typical radiological picture. 

Histological examination of the bone of patients with secondary hyperparathyroidism demonstrates that the edges of the bone trabeculae are sometimes eroded. Rows of osteoclasts are lined along the edges. Some areas of the bone which have been completely... 

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. 

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. 

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