In the course of our studies in calciulm metabolism evidence has steadily accumulated that the metabolism of acid-producing substances plays an important r6le in influencing the assimilation and excretion of calcium. This effect, however, has not been adequately studied in man, and in other studies of calcium exchange the potential acidity or alkalinity of foods and medication has largely been neglected.It is the purpose of the present investigation to follow the effect of food-stuffs and inorganic salts on calcium metabolism with relation to their potential acidity (after oxidation) referred to the hydrogen ion concentration of the blood.Studies in rickets for some time have indicated the importance of acidity to the assimilation and storage of inorganic salts in bone. Thus, McClendon (1) noted that the addition of alkali to a diet increased its power to produce rickets and, conversely, Zucker, Johnson, and Barnett (2) reported that the change in acidity of diets from the alkaline toward the acid side of neutrality might result in healing of the rachitic lesions.Much work, too, has been done upon the effect of administered acid on the mineral excretion. The experiments of Givens and Mendel (3) and of Givens (4) upon the effect of base and acid on the general metabolism tended to minimize variations in calcium excretion resulting from this factor. Subsequently, Goto (5), using rabbits, demonstrated depletion of the skeleton by repeated doses of hydrochloric acid. Lamb and Evvard (6) demonstrated increased urinary calcium

Most of the calcium of the body is found combined with phosphate in the skeleton but phosphorus in one form or another is present in relatively large quantities in all body tissue. Any gross change in calcium metabolism must of necessity affect the phosphorus output. It might be possible, however, for considerable changes to occur in phosphorus metabolism without any great effect on the calcium balance,In the metabolism of bone the two elements are closely associated and under certain abnormal conditions their mutual interdependence is strikingly demonstrated. It has been clearly shown, for instance, (1,2,3,4,5,6) that in growing animals the ratio of these two elements in the diet is of the greatest importance and that in the absence of the controlling influence of vitamin D any great departure from the optimal relationship of calcium and phosphorus in the food results in the development of rickets. In the rachitic child or rat, also, Karelitz and Shohl (7) and Shohl and Brown (8) found that the ingestion of added phosphate brought on tetany with the characteristic fall in serum calcium and rise in serum phosphorus.It is well known that in many conditions there is a definite relationship between the values for calcium and phosphorus in the serum.3 In 1 Aided in part by a grant from the Lead Fund of Harvard University.

In the investigation of various problems of calcium and phosphorus metabolism, it has been found that great changes in the volume and direction of the calcium and phosphorus stream may occur without any notable difference in the serum levels of these elements. In hyperthyroidism the calcium excretion in the urine is relatively huge and there are large negative balances of calcium and phosphorus, yet the serum calcium and serum phosphorus' remain within normal limits (1). Moreover, there is no appreciable change in the serum levels of healthy people when, by changing the calcium intake, a positive balance is shifted to a negative one or vice versa.Yet the actual and relative amounts of calcium and phosphorus in the serum is of the utmost importance in certain abnormal conditions. MacCallum and Voegtlin (2) described the low blood and tissue calcium associated with tetany after removal of the parathyroids.Greenwald (3) later demonstrated the associated rise in serum phosphorus and since that time the high phosphorus, low calcium of the serum in many types of tetany has come to be recognized. Marriot and Howland (4), DeWesselow (5) and others have found a similar relationship of the serum values in terminal nephritis. On injection of large amounts of inorganic phosphate into dogs Binger (6) produced tetany with a low serum calcium and high serum phosphorus. Similar results have been found to follow injection or ingestion of very large quantities of phosphate by numerous investigators (7,8,9). The 1 Throughout this paper the term "serum phosphorus" is used in referring to serum inorganic phosphorus.

The bones may well be looked upon as a storehouse for calcium and phosphorus, readily available for the body needs for fixed base. The demands upon this supply can readily be determined if a carefully controlled diet inadequate in calcium is administered. Under such conditions the normal excretion of calcium remains fairly constant, and a comparison with disease states may readily be undertaken.For several years this laboratory has systematically studied the calcium and phosphorus exchange in numerous pathological conditions. In the course of these studies various diseases have been investigated and are to be published (1, 2, 3).We have also had the opportunity to investigate many interesting diseases in which a disturbance of bone metabolism might well be expected. Some of these isolated cases are here brought together and this paper, therefore, demonstrates the metabolic need of calcium and phosphorus in various bone abnormalities as well as in gout and chronic hepatitis with jaundice. EXPERIMENTAL METHODSThe patients were, with one exception, studied in the metabolism ward at the Massachusetts General Hospital. The careful management and routine used there for the preparation of accurate diets and for the collections of urine and feces has already been fully described (4). The periods used here were of three days' duration, and the feces were divided by the appearance of carmine. The methods of analysis for calcium and phosphorus were those of Fiske (5) and the nitrogen determinations were made by Kjeldahl method. In order to determine the endogenous need for calcium the patients received our usual neutral diet, which is inadequate only in calcium. In nine normal control subjects on similar neutral diets, the excretion of calcium averaged 186 mgm. in the urine and 386 mgm. in the feces per period.A. DISEASES AFFECTING THE SKELETON Secondary carcinoma involving bone In the course of studies on the effect of lead therapy upon cancer growth, observations were also made upon the calcium and phosphorus 235

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