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It is now established that the biological activity of cholecalciferol (vitamin D3) results from a series of metabolic conversions to more active compounds. (1–3) The first of these con-versions is hydroxylation of D3 to 25-hydroxycholecalciferol (25-HCC), which occurs in the liver. Further metabolism to dihydroxy metabolites (1,25-DHCC, 24,25-DHCC and 25,26-DHCC) then occurs. The synthesis of 1,25-DHCC probably takes place exclusively in the kidney (4), since its production becomes un-detectable after nephrectomy. Synthesis of 24,25-DHCC also occurs in the kidney, but possibly also in other sites such as intestine (3) and cartilage (5), both of which can convert 25-HCC to 24,25-DHCC in vitro. The site of synthesis of 25,26-DHCC is un-known. The dihydroxymetabolite which has aroused the greatest interest is 1,25-DHCC, since it appears to be the major bio-logically active form of the vitamin. Thus at low doses it promotes the intestinal absorption of calcium and phosphate in vitamin D deficient animals or birds, and it increases mobilisation of calcium from bone and heals rickets. The rate of production of 1,25-DHCC is closely controlled by various factors, and it has therefore been considered a hormone derived from the kidney which acts in concert with parathyroid hormone (PTH) and calcitonin (CT) to regulate calcium metabolism. Defective synthesis of 1,25-DHCC, despite adequate supplies of the parent vitamin D3, is thought to contribute to the abnormalities of mineral metabolism in a number of clinical disorders, including chronic renal failure (6), vitamin D-dependent rickets (7), hypoparathyroidism and pseudo-hypoparathyrodism (8).

In experimental animals a major effect of the administration of calcitonin (CT) is to inhibit bone resorption and this property has led to its use in man to suppress excessive bone turnover in Paget’s disease and other disorders (1–4). On the other hand, the role of endogenous CT in the pathogenesis of bone disease has remained unresolved. The present studies were designed to examine the relationships between plasma immunoreactive CT (iCT), parathyroid hormone (iPTH) and bone disease in chronic renal failure.

Inorganic phosphate (Pi) has long been known to play an important role in biological systems. It is essential for structural integrity of cells, for example, as a constituent of membrane phospholipids. It is also involved in a host of anabolic and catabolic processes. In glycolysis, Pi participates in the degradation of glucose and synthesis of ATP. Pi has an important role in the regulation of the activity of many enzyme systems involved in energy-transforming reactions. In erythrocytes, through its regulation of the levels of 2,3-DPG (2,3-diphosphoglycerate) and ATP, Pi is indirectly involved in the delivery of oxygen to tissues (1). In urine, Pi is the major buffer system. In hypophosphatemic states, phosphate deficiency leads to many metabolic disturbances, including myopathy, haemolysis and impaired phagocytosis (2).

The concept of interactions between cells of the immune system and bone in the control of bone turnover is far from new. The relationship between haematopoietic precursor cells and the osteoclast has long been recognised and studies on animals with congenital bone diseases such as osteopetrosis have identified defective components of the immune system as causing or contributing to the disease. For example, the op/op (osteopetrotic) rat exhibits thymic atrophy and the disease can be cured by either administration of normal bone marrow cells or by thymus transplant l. Several mutant rodents have been described in which the osteopetrosis can be cured by injection of bone marrow, spleen or thymocytes l. These studies suggest that a functioning immune system is necessary for the normal activity of the bone resorbing cells.

Phosphorus plays an important role in a variety of biological systems. It occurs in structural components such as phospholipids, and in other important cellular constituents, eg, nucleic acids, nucleotides, proteins, sugars etc. It is involved in the regulation of many metabolic pathways(1).