RAREFYING DISEASE OF THE SKELETON 433 



CLF fed a low-calcium diet continued to lay heavily and produced 

 well calcified eggshells. Normal birds produced one or two thin- 

 shelled eggs and discontinued ovulation when the intake of calcium 

 was restricted. Taylor et al. ( 1962) suggested that the pituitary cut- 

 off mechanism was generally verv efficient, but lines bred for inten- 

 sive laying continued to ovulate when transferred to a low calcium 

 intake, and it was these individuals that were susceptible to CLF. 

 Restriction in cages and insufficient physical activity was an impor- 

 tant factor in CLF; some birds recovered simply by being released 

 to exercise ad libitum. Thus, in birds as in humans, calcium-deficient 

 diet and sedentary life were precipitating factors in the pathogenesis 

 of osteoporosis, but the main cause was unknown, although probably 

 genetic in origin. 



Silberberg and Silberberg (1962) reported that senile osteoporosis 

 in mice is associated with genetic factors. The DBA strain was more 

 susceptible than other inbred strains to a disorder characterized by 

 thin, rarefied, deformed bones appearing between 24 and 36 months, 

 an advanced age for mice. Young rats fed diets with less than 0.1 

 per cent calcium and some vitamin D develop osteoporosis that is 

 cured by treatment on high calcium intake (McClendon et al., 

 1962). During adult life, rats retain their bone mass more tenaciously 

 than other mammals, and are generally resistant to osteoporosis 

 (Nicolaysen, 1960). Despite continuous administration of cortisone, 

 in doses that produce osteoporosis in birds, mice, rabbits, and man, 

 rats will retain the bulk of the calcium in the skeleton. Caldwell 

 ( 1962a ) noted that cortisone inhibits bone growth, but the effect 

 in rats is temporary, and these animals develop resistance to the 

 hormone. Furthermore, by measuring the amount of calcium per 

 gram of wet weight of whole bones, Caldwell (1962a) observed 

 that adrenalectomy and orchiectomy destroyed the resistance to 

 cortisone, and high calcium intake did not prevent or cure the 

 osteoporosis. Urist, MacDonald, Johnson, Deutsch, and Vincent 

 (unpublished) performed similar experiments and measured the 

 capacity of the adreno-orchiectomized rat to retain an injection of 

 Sr''"', but found no significant abnormality of bone. Nevertheless, 

 adrenalectomized animals are more generally sensitive than normal 

 animals to cortisone, and further experiments on osteoporosis in 



