Osteoporosis in Adrenal Insufficiency: Could Metformin be Protective?

Adrenal insufficiency (AI) is a serious disorder characterized by the adrenal glucocorticoid deficiency. Regardless of the etiology, AI patients need long-term replacement therapy for glucocorticoids and, in some cases, for mineralocorticoids. The replacement therapy cannot completely mirror the physiological secretion patterns, and therefore, glucocorticoid excess is a common sequela in AI patients. Moreover, due to the absence of the reliable clinical markers to monitor the adequacy of the replacement therapy, clinicians often over-treat the AI patients to avoid adrenal crisis. Long-term glucocorticoid use is associated with the loss of bone density and osteoporosis, increasing the risk of fractures. Moreover, glucocorticoid-induced hyperglycemia and type 2 diabetes mellitus further aggravates the bone disorders. In the recent years, ameliorating effects of metformin on glucocorticoid-induced bone disorders, as well as hyperglycemia, have been reported by a multitude of studies; and here, we reviewed and discussed the most recent findings regarding the positive effects of metformin on alleviating the bone disorders, and their implications in the AI patients.