Further studies of the effects of citrate feeding on the calcium, phosphorus, and citrate metabolism of rachitic infants

Abstract

Summary Observations were made on three rachitic infants during the course of treatment with a citrate mixture without vitamin D. The studies included determinations of calcium, phosphorus, citrate, and phosphatase in the serum and the daily excretions of calcium, phosphorus, and citrate in the urine. X-rays of the long bones were taken at intervals so that the evidences of deposition of bone salt in the rachitic cartilage could be correlated with the concentrations of calcium and phosphorus in the serum. The citrate solution consisted of an equimolar mixture of citric acid and trisodium citrate which was added to the milk feedings in amounts ranging from 30 to 60 mM. of citrate per day. In two infants with advanced floridrickets citrate administration resulted in a rapid drop of the concentrations of serum calcium to hypocalcemic levels while the serum phosphorus values remained low. Deposition of bone salt in the rachitic cartilage was evident by x-ray during the period in which the concentrations of calcium and phosphorus in the serum were below the normal range and Ca×P ratios were less than 30. The urinary excretion of calcium remained low during the period of citrate treatment and the urinary excretion of phosphorus was unchanged. The concentrations of citrate in the serum were not consistently increased during citrate treatment but rose after vitamin D was given. A third infant with early ricketsand tetany showed a somewhat different pattern of response to citrate feedings. The serum calcium level which had risen following high calcium intake decreased somewhat when citrate was given but the concentration of phosphate and of citrate rose to normal values while the alkaline phosphatase activity in the serum decreased. X-rays of the bones showed normal growth and calcification during the period of citrate therapy without vitamin D. It is suggested that the antirachiticeffect of citrate feeding is not simply due to the formation of a diffusible calcium citrate complex in the intestinal contents, nor in the extracellular fluids, but that there is a local action upon proliferating cartilage and bone matrix resulting in increased calcifiability. An analogy is drawn between the sequence of events following citrate feeding to rachitic infants and that seen in patients with decalcification of the skeleton due to hyperparathyroidism when the hyperfunctioning parathyroid tissue is removed. In both instances mineralization of the skeleton is associated with decreased levels of calcium and phosphorus in the serum. In one patient of this series, however,a 2-month-old infant with early rickets, citrate feeding seemed to be a more complete substitute for vitamin D. While on citrate therapy the levels of serum phosphorus and of citrate rose to normal; the alkaline phosphatase activity of the serum decreased; and bone x-rays showed normal ossification. This is another suggestion of an interrelationship between citrate metabolism and the physiological effects of vitamin D.