Calcitonin and parathyroid hormone: an evening seminar of the 17th Annual Meeting of the Japanese Society for Bone and Mineral Research, July 29, 1999.

Abstract

and neurodegenerative diseases as a consequence of the paradoxical calcium overload due to age-related calcium deficiency. The main biologic action of calcitonin has resulted from its successful use in disease states characterized by increased bone resorption. Calcitonin is approved by the Food and Drug Administration (FDA) for the treatment of osteoporosis. The main biologic effect of calcitonin is to inhibit osteoclastic bone resorption. This effect is mediated by a calcitonin receptor, which is strongly expressed by osteoclasts. Thyroid C cells, which are neural crest derivatives, are the primary source of calcitonin in mammals. However, other tissue sources of calcitonin have been described, notably the pituitary cells and widely distributed neuroendocrine cells. Since the concentration of calcitonin at its several sites of biosynthesis may be sufficiently high, calcitonin may be expected to have paracrine effects at these sites. The demonstration of calcitonin and its receptors at intracranial sites may qualify calcitonin as a neurotransmitter. Most investigators find that women have lower calcitonin levels than men. The mechanism for this difference may be accounted for in part by a stimulating effect of gonadal steroids on calcitonin secretion. Analgesia is a commonly reported effect of calcitonin treatment in osteoporosis and bone malignant metastasis. In experimental studies using animals, calcitonin has acute antinociceptive effects when administered into the central nervous system. However, the effects of centrally administered calcitonin do not necessarily explain the clinical effects of intramuscular calcium injections. In this symposium, Dr. Yoshimura further focuses on the modulation of pain sensation at the level of the spinal cord in cases where there is an estrogen deficiency. By using a rat model, he initially observed the inducement of hyperalgesia after ovariectomy and the antinociceptive effect after intramuscular injections of elcatonin. He confirmed the involvement of the Parathyroid hormone and calcitonin are the principal regulators of bone and calcium metabolism in humans and most likely all terrestrial vertebrates. In bone, parathyroid hormone stimulates the resorption of bone, releasing calcium and phosphate. In the kidney, this hormone stimulates the reabsorption of calcium and inhibits the reabsorption of phosphate. Parathyroid hormone stimulates the activity of renal 1-αhydroxylase, thereby enhancing synthesis of the active form of vitamin D, which in turn increases intestinal calcium and phosphate. As a result of these parathyroid hormone-dependent actions, blood calcium concentration increases and phosphate concentration decreases. The extracellular calcium concentration is the most important regulator of parathyroid hormone secretion, and it is maintained at a constant level despite variation in the amount of daily calcium intake. In chronic calcium-deficient conditions, however, the homeostatic regulation of extracellular calcium level by parathyroid hormone seems to threaten the skeleton and nonskeletal soft tissues as well. Increased parathyroid hormone secretion readily leads to osteoporosis, which is a decrease in bone calcium content. On the other hand, a variety of cells in the extraskeletal soft tissues are exposed to the constant calcium overflow from bone so their intracellular calcium levels tend to increase. As a consequence, serious disturbance of cell function occurs, giving rise to various diseases. While systemic calcium deficiency is certainly expected to cause skeletal calcium deficiency, the associated increase of calcium within cells of nonskeletal tissue may appear to be paradoxical. In this symposium, Dr. Fujita focuses on this paradoxical calcium overload of the nonskeletal tissues and relates it to calcium deficiency. He attempts to explain the cause of various soft tissue disorders including cardiovascular diseases