Adrenal Function and Skeletal Regulation

The hormones produced by the adrenal gland have important effects on the bone both in physiological and pathological conditions. The role of cortisol secretion on the bone physiology during growth is not fully understood. During the adult life, the degree of the cortisol secretion, still in the normal range, seems to directly correlate with the bone mineral density in elderly individuals and in osteoporotic women. The overt and subclinical cortisol excess leads to an increased risk of fracture partially independent of the bone mineral density reduction and possibly related to a reduced bone quality. The individual sensitivity to cortisol due to the different polymorphisms of the glucocorticoid receptor (GR) or of the 11β-hydroxysteroid dehydrogenase may modulate the effect of glucocorticoids (GCs) on the bone, thus explaining, at least in part, the wide interindividual variability of the skeletal consequences of the hypercortisolism. The adrenal androgens excess in congenital adrenal hyperplasia (CAH) importantly affects the bone, leading not only to an early growth acceleration but to a reduction in the final adult height. On the other hand, the reduction of the adrenal androgens during aging has been considered among the pathophysiological mechanisms of the osteoporosis in the elderly, but the effects of the restoration of the androgen levels in the aging-related osteoporosis are conflicting. Finally, the presence of mineralocorticoid receptors has been demonstrated in osteoblast, osteoclast, and osteocyte, and an association exists between indexes of bone strength and some genes involved in aldosterone pathways. In keeping, the condition of hyperaldosteronism has been associated with an increased fracture risk.