Glucocorticoids, vitamin D and bone : a pathophysiologic and therapeutic study of glucocorticoid-induced bone disease

Mooser's report ( 1921) of a patient with osteoporosis and obesity is one of the first descriptions of endogenous hypercortisolism. Later Cushing (1932) described the syndrome as a clinical entity and Albright et al. (1941) reported 9 patients who at autopsy all appeared to have sustained a severe degree of cortical and trabecular bone loss. In 1949 glucocorticoids (GC) became available as therapeutic agents. in addition to their favourable antiinflammatory action deleterious side effects (e.g. on bone mass) have become apparent (Kjellstrand, 1975). A diminished bone mass, measured as trabecular bone volume of iliac crest biopsies (Birkenhager et al., 1967) or by total body Ca with neutron activation analysis (Aloia et al., 1974), is a typical hallmark in patients with endogenous hypercortisolism. The impact of exogenous GC excess on bone mass is more difficult to evaluate. In the quantification of the amount of bone in such patients by several techniques one has to take into account not only the physiological age related bone loss (see Chapter II), but also the underlying disease for which GC are prescribed. This is illustrated by Stresemann & Krokowski ( 1967) who found signs of a decreased bone mineral content on X-rays of the vertebral column (using a quantitative measurement technique) in 32% of patients treated with varying doses of GC for chronic obstructive lung disease, but similar signs were observed in an equal percentage of patients who never had used steroids. However, Adinof & Hollister (1983) described a significant loss of trabecular bone mass at the metaphysis of the radius with single photonabsorptiometry only in asthmatic subjects on long-term daily steroids. Measurement of total body Ca with neutron activation analysis showed lower values in patients with rheumatoid arthritis treated with non steroidal antiinflammatory drugs than controls, but even lower values in rheumatic patients treated with steroids (Reid et a!., 1982). Similar findings were reported by Hahn et al. (J 973) with photonabsortiometry of the metaphyseal mass of the forearm. The decreased mineral content was correlated with the duration of GC therapy