434 URIST, MACDONALD, MOSS, AND SKOOG 



cortisone-treated adrenalectomized rats would be of great interest. 

 The possibility of an antiosteoporosis factor present in normal adult 

 males, and essential for bone retention during aging, requires inten- 

 sive investigation (Urist, 1960/^, 1962). 



The action of adrenal cortical hormone upon bone in rats was 

 attributed to inhibition of absorption of calcium from the intes- 

 tinal tract or physiologic calcium deficiency. Malabsorption was 

 assumed to stimulate the parathyroids and lead to osteoporosis. 

 Clark and Smith (1962), however, noted hypercalciuria in parathy- 

 roidectomized rats, the same as in normal rats, and Clark and Roth 

 (1961) concluded that hvdrocortisone decreased the reabsorption 

 of calcium and phosphate by the kidney tubules. Under these condi- 

 tions, weanling rats increased the density of their bones, but grew 

 at a rate so much less than normal that presumablv the over-all re- 

 tention of calcium was less. The reaction of the skeleton has long 

 been known to be entirely different before and after a rat reaches 

 maturity and the plateau of growth, and the endocrine relations 

 were difi^erent in many respects in rats, other rodents, and higher 

 mammals. Calcium deficiencv was a contributing factor in the de- 

 velopment of osteoporosis; Storey (1961) fed low-calcium diets to 

 rabbits treated with cortisone and described osteoporosis associated 

 with extensive osteoclastic activity and secondary hyperparathyroid- 

 ism. 



How endocrine interrelationships influence osteoporosis in man is 

 not known. Schlesinger et al. (1961) observed that adrenal steroids 

 produce osteoporosis in children and postmenopausal women more 

 frequently than in men, and generally from treatment on lower 

 doses and in less time. It could have been argued that the reason 

 is simply that young adults have more bone to begin with than 

 children and senile women. However, the subject was considerably 

 more complex; 85 per cent of the patients of comparable ages and 

 skeletal conditions did not develop osteoporosis on comparable 

 steroid therapy. Other, as vet unknown, factors were evidently of 

 primary importance. 



Kao et al. (1962) reported that the glycoprotein decreased in 

 bone and increased in costal cartilage in rats in the process of aging 

 between 1 and 36 months. Previouslv, Sobel et al. ( 1954), Sobel and 



