Corticosteroid-induced osteoporosis

Glucocorticoid-induced bone loss has been recognized for almost 50 years, yet it remains an important medical problem and a common cause of fracturing. Loss of skeletal mass may occur early in the course of glucocorticoid therapy and appears to be related to the cumulative dose of steroid, as well as to the usual risk factors for osteoporosis. The pathophysiology of this disorder is poorly understood, but available information suggests that glucocorticoids exert direct and indirect actions on bone and calcium homeostasis that may contribute to osteopenia. Direct effects appear to occur soon after the initiation of glucocorticoid therapy and include (1) suppression of intestinal calcium absorption, (2) decreased renal tubular calcium resorption with increased urinary calcium excretion, and (3) suppressed osteoblast function and decreased bone formation. Ultimately, renal and intestinal losses of calcium result in the development of secondary hyperparathyroidism, which, in concert with stimulation of parathyroid secretion and an increased sensitivity of bone cells to PTH, produces an increase in bone resorption and bone turnover. Although effective forms of prevention and treatment have not been identified, available information provides a rationale for the use of calcium supplements, maintenance of vitamin D nutrition, and the use of agents that suppress bone resorption and bone turnover. The use of sodium fluoride to stimulate bone formation has not been fully tested in this condition and it remains an investigational agent. Although recent advances in our understanding of the glucocorticoid receptor are likely to lead us to new therapeutic approaches, present methods of prevention and treatment have not been adequately evaluated and await prospective study.