EFFECTS OF INANITION ON THE BODY AS A WHOLE 107 



etiology of rickets has been much disputed. It has generally been held to be due 

 to dietary insufficiency of some kind, although infection, toxins, or bad hygienic 

 conditions in general have been frequently considered primary factors, even 

 down to the present (Looser '20; Paton and Watson '21). Esser ('07) claimed 

 the production of rickets by overfeeding in young rats; and it has even been 

 observed to appear spontaneously in this species by Erdheim ('14) and Pappen- 

 heimer ('14). Some consider that rickets is produced indirectly through effects 

 on the endocrine system (Stoeltzner, '21). 



Among those who consider rickets to be caused by dietary deficiency, 

 there have been varied opinions as to what factor is deficient. For human 

 rickets, a deficiency in fats was sometimes held responsible (Vincent '04, 

 Cheadle and Poynton '07; opposed by Hutchinson '20 and others); although 

 mineral deficiency has frequently been suspected, especially in rachitoid dis- 

 orders in animals, such as that in cattle described by Lotsch andLange ('12). 

 Lehnerdt ('10) and Rohmann ('16) hold that rickets or "pseudorickets" may 

 be caused by (1) deficiency of calcium salts in the diet; (2) deficient calcium 

 absorption in the intestine; (3) excessive calcium excretion; or (4) defective 

 calcium assimilation by the osteoblasts. The disputes as to whether the dis- 

 orders produced by calcium and phosphorus deficiencies in animal diets are 

 really identical with human rickets will be discussed in the chapter on the 

 skeletal system. 



Recently the controversy has shifted to the question concerning the causa- 

 tion of rickets by deficiency in vitamin A, which was advocated by Mellanby 

 ('19), Nathan ('20), Higier ('22) and others; but was opposed by Hess and Unger 

 ('19), Hess, McCann and Pappenheimer ('21), Mackay ('21), Paton and Watson 

 ('21, '21a) and others. It may be stated here, however, that the most recent 

 work on experimental rickets by E. Mellanby ('21), Sherman and Pappenheimer 

 ('21) and by McCollum and his associates indicates strongly that the cause of 

 rickets is not a single deficiency, but it is complicated in character and dependent 

 upon various factors. For puppies, Mellanby ('21) considers the following 

 as important: (1) a deficiency of calcium and phosphorus in the diet; (2) 

 a deficiency of fat containing the antirachitic vitamin; (3) excess of bread, other 

 cereals and carbohydrates; (4) absence of meat; (5) excess of the protein portion 

 of caseinogen, free from calcium; (6) confinement. McCollum and his coworkers 

 have recently shown that in young rats the experimental production of rickets 

 (or closely allied conditions) depends largely upon the calcium-phosphate ratio 

 in the diet, either low calcium or low phosphorus being effective, in the absence 

 of a "fourth vitamin" (distinct from, though closely associated with vitamin A) 

 which promotes calcium deposition in ossifying tissues (McCollum, Becker and 

 Simmonds '22, '22a; McCollum '23). Byfield and Daniels ('23) found it impos- 

 sible to produce typical rickets in rats on diets low in calcium, phosphorus or 

 butter fat, except when the experiment was extended to the second generation. 

 Chick et al. ('23) conclude from clinical observations and animal experiments 

 that the three main factors in the etiology of rickets are (1) an organic dietary 

 factor concerned with the calcification of bone; (2) light; and (3) the amount and 

 relative proportions of calcium and phosphorus in the diet. An extensive 



