232 



E. C. NORDIN 



That Cushing's syndrome is associated with osteoporosis is beyond doubt, but 

 whether therapy with synthetic corticosteroids has the same effect is a little less 

 certain, although extremely probable. The first cases of osteoporosis from cortico- 

 steroid therapy were described by De Martini et al. in 1952 and further cases were 

 reported by Curtis et al. (1954) and then by many others. McConkey et al. (1962) 

 on the other hand reported that the incidence of osteoporosis was no higher in a 

 series of patients with rheumatoid arthritis on steroid therapy than in a similar group 

 untreated, but they are probably in a minority. 



The cause of the osteoporosis in these patients is uncertain. The measurement of 

 bone formation rate with bone-seeking isotopes has not yielded a clear answer. Thus 

 GoRDAN and Eisenberg (1963), using stable strontium, found small pool sizes and 

 turnover rates in three cases of Cushing's syndrome. The 

 '""^ ''^ same authors studied a large number of patients taking 



synthetic corticoids and found variable pool sizes but gen- 

 erally an increase in urinary excretion and bone accretion 

 rates. We have measured bone formation rate by a variety 

 of techniques but have failed to find any consistent differ- 

 ence between the rates in normal and steroid-treated in- 

 dividuals. Using intravenous radiocalcium or radiostrontium 

 (Nordin et al., 1963), our values ranged from about 2 to 

 10 mg./kilo in normal subjects and extended over a similar 

 or rather larger range in patients on steroid therapy (Fig. 6). 

 Measurement of retention in a whole body counter yielded 

 lower values but again there was no difference between the 

 controls and the patients on corticosteroids (Fig. 6). Even 

 with continuous feeding of radiocalcium (Nordin et al., 

 1964) the bone mineralisation rate appeared to be normal 

 in patients on steroid therapy. 



Balance studies in patients on steroid therapy have also 

 been somewhat inconclusive. Slater et al. (1959) observed 

 malabsorption of calcium in patients on dexamethasone. 

 We have observed the same thing occasionally but not con- 

 sistently. There is a tendency for both faecal and urinary 

 calcium to be higher than normal in patients on steroid 

 therapy and the theoretical mean calcium requirement (i.e. 

 the level at which calcium intake and output are equal) is 

 therefore somewhat increased but the significance of this 

 is uncertain. Radiocalcium absorption studies have also 

 been rather inconclusive although the results tend to be low particularly in 

 patients on cortisone (Nordin, 1964). In animals, Stoerk et al. (1963) implied 

 that hydrocortisone interfered with calcium absorption but suggested that it also 

 interfered with the action of parathyroid hormone on bone whereas Clark and 

 Smith (1964) were unable to demonstrate any efFect of corticosteroids upon calcium 

 absorption. 



Stoerk et al. (1963) showed that hydrocortisone could lower the plasma calcium 

 and plasma citrate of parathyroidectomised rats and suggested that failure to observe 

 the same effect in normal animals was due to secondary hyperparathyroidism. They 



