Glucocorticoid-induced osteoporosis: mechanisms, management, and future perspectives.

Glucocorticoids are widely used for their unsurpassed anti-inflammatory and immunomodulatory effects. However, the therapeutic use of glucocorticoids is almost always limited by substantial adverse outcomes such as osteoporosis, diabetes, and obesity. These unwanted outcomes are a major dilemma for clinicians because improvements in the primary disorder seem to be achievable only by accepting substantial adverse effects that are often difficult to prevent or treat. To understand the pathogenesis of glucocorticoid-induced osteoporosis, it is necessary to consider that the actions of glucocorticoids on bone and mineral metabolism are strongly dose and time dependent. At physiological concentrations, endogenous glucocorticoids are key regulators of mesenchymal cell differentiation and bone development, with additional regulatory roles in renal and intestinal calcium handling. However, at supraphysiological concentrations, glucocorticoids affect the same systems in different and often unfavourable ways. For many years, these anabolic and catabolic actions of glucocorticoids on bone were deemed paradoxical. In this Review, we highlight recent advances in our understanding of the mechanisms underlying the physiology and pathophysiology of glucocorticoid action on the skeleton and discuss present and future management strategies for glucocorticoid-induced osteoporosis.

Source: Lancet




Glucocorticoid-Induced Cushing Syndrome Linked to Increased Risk for CV Events .

Among patients taking glucocorticoids, those who develop iatrogenic Cushing syndrome have more than twice the risk for cardiovascular events as those who do not develop the condition, according to a BMJ study.

Using national U.K. databases, researchers studied some 550 patients who exhibited Cushing syndrome while taking glucorticoids, 3000 taking glucocorticoids who did not develop Cushing syndrome, and 3000 not taking the drugs. In adjusted analyses, the rate of cardiovascular events per 100 person-years was 15.1 among patients with Cushing syndrome, 6.4 among glucocorticoid users without Cushing syndrome, and 4.1 among nonusers.

The authors write: “Glucocorticoid induced cushingoid appearance should no longer be considered as a minor adverse event of glucocorticoids.” They add that those who do exhibit Cushing syndrome “should be aggressively targeted for early screening and management of cardiovascular risk factors.”

Source: BMJ