Stanley Wallach

Metabolic effects of synthetic salmon calcitonin in Paget's disease of bone

Abstract The initial effects of synthetic salmon calcitonin (SCT) given as a single subcutaneous injection of 50 or 100 MRC units daily or three times a week were studied in ten patients with Pagets disease of bone. Positive shifts in calcium balance and/or a decrease in the rate of radiocalcium tumover were prominent effects in nine patients. Serum alkaline phosphatase did not change significantly and urinary total hydroxproline excretion decreased an average of 20% during the initial 28 days of SCT administration. A comparison of the combined radiocalcium turnover and calcium balance data indicated effective inhibition of bone resorption in eight of ten patients. The changes in skeletal metabolism were similar with the smallest dose employed, 50 MRC units three times a week compared to the largest dose, 100 MRC units daily. Significant natriuresis and a reduction in the degree of positive sodium balance were observed in three patients. These data are compatible with other studies indicating that SCT is more potent in the human than porcine calcitonin, by approximately 20-fold on a molar basis, and 50 MRC units of SCT three times a week appears to be an effective dose in initiating treatment of Pagets disease.

Tissue distribution and transport of electrolytes Mg28 and Ca47 in hypermagnesemia.

The effect of acute hypermagnesemia (9–14 mEq./L.) on the distribution of electrolytes Mg28 and Ca47 in various tissues was studied in renal-ligated dogs. The sodium content of 5 of 8 tissues was decreased by 10–30 per cent, the potassium content of 3 tissues was increased 5–30 per cent and the acid-soluble phosphorus concentration of 2 tissues was decreased by 15 per cent. Total and/or exchangeable cellular concentrations of calcium were decreased by 25–35 per cent in skeletal muscle, myocardium, brain and pancreas. Total and/or exchangeable cellular concentrations of magnesium were increased by 8–50 per cent in skeletal muscle, nerve, pancreas and aorta and were unchanged in liver, myocardium and brain. These data suggest that magnesium has inhibitory effects on the cellular transport of electrolytes which are similar to those of calcium. The cellular influx of calcium is inhibited by magnesium. The stability of the cellular concentrations of magnesium in relation to the degree of hypermagnesemia is compatible with in vitro studies in rat liver indicating that the fractional rate of cellular influx of magnesium is decreased and the fractional rate of cellular efflux of magnesium is increased during extreme hypermagnesemia.

Effects of porcine calcitonin in osteogenesis imperfecta tarda.

The effect of the administration of porcine calcitonin to two children with osteogenesis imperfecta tarda was evaluated by means of calcium and phosphorus balance studies, urinary hydroxyproline excretion, tubular reabsorption of phosphorus, and phosphate clearance before and after administration of parathyroid extract. The balance studies indicated that calcitonin was effective in causing retention of calcium and phosphorus and decrease in hydroxyproline excretion. These improvements suggest that calcitonin may be of therapeutic value in osteogenesis imperfecta by decreasing bone resorption.

Radiomagnesium turnover studies in hypomagnesemic states.

Magnesium deficiency usually although not invariably results in hypomagnesemia. Alcoholism is the most common cause of hypomagnesemia; and on the basis of demonstrated magnesium retention during repletion, a low urinary excretion of magnesium which does not increase proportionately during intravenous administration of magnesium, a low calculated exchangeable body pool o€ magnesium, and isolated reports of muscle depletion of magnesium, it has been assumed that the hypomagnesemia of alcoholism does indeed reflect body deficiency of These characteristics, however, have not been found in all alcoholics with hypomagnesemia.6 Although considerably fewer studies have been reported in subjects with intestinal malabsorption and hypomagnesemia, magnesium deficiency has also been assumed to be present.-O In contrast, in hyperthyroidism, a third condition in which hypomagnesemia sometimes occurs,11J2 a multiplicity of variables are present, including an increased intake of magnesium, an augmented urinary excretion of magnesium, and a stimulation of transport of magnesium, and there is little evidence to suggest that true body depletion of magnesium exists despite hypomagnesemia In studies in our laboratory of uremic subjects with hypermagnesemia, it was found that the exchangeability of magnesium, as derived from a digtial computer analysis of plasma specific activity curves of Mg-28, was normal, suggesting that a control mechanism was operative which influenced the fractional cellular transport of magnesium reciprocally to the extracellular concentration of magnesium and protected the tissues from a surfeit of magnesiurn.I5 Because of these findings, it was decided to apply a similar technique to hypomagnesemic human subjects in an attempt to define the status of magnesium exchange in hypomagnesemia and to determine whether a similar control mechanism was discernible in hypomagnesemia. The technique involved the intravenous administration of 50 to 100 p c of high specific activity Mg-28 (200 pc/mEq) and a determination of the plasma specific activity and urinary excretion of Mg-28 and total magnesium over the next 72 hours.I5 In the few cases in which it was studied, including subjects with overt malabsorption, fecal Mg-28 was found to be negligible and never exceeded 3% of the injected dose. The experimental group consisted of eight alcoholic subjects with hypomagnesemia, three alcoholic subjects with normomagnesemia, one hypomagnesemic subject with periostitis of unkriown etiology and hypercalcemia (L.B.) , and one normomagnesemic subject with chronic, severe malabsorption, who had hypomagnesemia prior to treatment with magnesium infusions and continued to retain 70% of therapeutic magnesium infusions up to the time of study (M.A.) . The alcoholic subjects were studied after two to nine weeks of hospital-