234 B. E. C. NoRDiN 



If there is some doubt about the effects of the corticosteroids on plasma calcium, 

 there is no doubt about their effect on plasma and urinary citric acid, which are 

 depressed by steroid therapy. This was reported in 1958 by Henneman and Henne- 

 MAN who stated that adrenocorticotrophic hormone and operative trauma both 

 lowered the serum concentration and urinary excretion of citric acid in man, and 

 confirmed by Agrell et al. (1961). 



Harrison (1959) found that administration of Cortisol to rats produced much 

 lower levels of citric acid in plasma than were found in rachitic or control animals. 

 Harrison and Harrison (1958) reported that this effect of Cortisol was attributable 

 to its inhibitory action on the eflux of citrate from cells to extracellular fluid rather 

 than to the intracellular accumulation of citrate. 



There is little doubt that corticosteroids tend to increase urinary calcium though 

 whether this action is direct or indirect it is impossible to say. According to Pechet 

 et al. (1959) the dose required to produce this effect is large but Laake (1960) 

 determined calcium clearance in 16 patients on corticosteroid therapy and found the 

 tubular reabsorption of calcium to be decreased in 7 of them. 



The effect of corticosteroids upon bone structure varies with the species studied. 

 Thus in Man the bone changes in Cushing's syndrome are essentially those of osteo- 

 porosis (Sissons, 1956) but the presence of normal osteoid seams and the occasional 

 slight increase in osteoclastic activity is perhaps slightly more in favour of increased 

 bone destruction than decreased new bone formation. This is also true in the rabbit in 

 which species Storey (1961) produced spontaneous fractures after 12 days of corti- 

 sone administration. This rapid rarefaction of bone was mainly due to an increased 

 rate of resorption associated with large numbers of osteoclasts at trabecular margins. 

 Old rabbits responded in the same way though rather more slowly. Urist and 

 Deutsch (1960) also demonstrated increased bone resorption by cortisone in birds. 

 The effects of corticosteroids on rat bone are more variable and are complicated by 

 the almost invariable interference with growth which this regime produces. Meta- 

 physeal sclerosis has been reported on cortisone treatment but this gave way to 

 osteoporosis when the Ca/P ratio of the diet was adjusted (Storey, 1961). 



To summarise the effects of corticosteroids on calcium and bone metabolism, it 

 would appear that they tend to inhibit calcium absorption, to inhibit renal tubular 

 reabsorption, to depress plasma calcium, and to depress plasma and urinary citrate. 

 Associated with these effects there is a tendency to negative calcium balance and the 

 development of osteoporosis which some workers attribute to reduced bone formation 

 but which experimentally seems more likely to be due to increased bone resorption. 

 In many ways their action is antagonistic to that of vitamin D and the parathyroid 

 hormone and it is possible that the interpretation of steroid action on bone may be 

 complicated by the frequent presence of secondary hyperparathyroidism. 



Growth hormone 



The effects of growth hormone on bone growth are too well known to require 

 detailed recapitulation. There occurs in acromegaly a "generalised overgrowth of 

 bone characterised by cortical thickening with circumferential increase and coarsening 

 of structure" (Finlay and MacDonald, 1954). These effects are understandable in 

 terms of the action of the hormone on growth processes in general. What is less easy 



