Glucocorticoids enhance bone resorption and decrease bone formation through their direct action on osteoblasts and osteoclasts and indirectly by inhibiting calcium absorption. Glucocorticoids inhibit the replication of the osteoblastic lineage, decrease the genesis of new osteoblastic cells, and induce apoptosis.

While the degree of glucocorticoid-induced bone loss is related to the total cumulative dose, bone loss is highest in the initial months of treatment (up to 30% in some studies). Initial loss is followed by slower, continuous bone loss. The extent of bone loss depends on the dose and duration of therapy. The typical risk factors for osteoporosis (e.g., age, sex or underlying disease) may have an independent and additive effect. For example, the risk of fragility fractures may be higher among postmenopausal women taking glucocorticoids. This emphasizes the importance of early preventive treatment and ongoing follow-up of patients on glucocorticoids.

Although glucocorticoids are the most common cause of secondary osteoporosis, diagnostic thresholds in glucocorticoid-induced osteoporosis, using BMD have not been established. The diagnostic guidelines for postmenopausal women do not apply to glucocorticoid-induced osteoporosis. At similar BMD levels, patients on glucocorticoids appear to have a higher risk of fracture. This higher risk of fracture at comparable BMD suggests that the quality of the bone tissue is affected by glucocorticoid therapy.

Patients who receive glucocorticoid therapy for 3 months should have a BMD measurement. Therapeutic intervention is recommended if the T-score is lower than -1.0. A n initial BMD determination should be obtained when patients initiate long-term (>6 months) glucocorticoid therapy. Monitoring may be repeated as often as every 6 months to detect bone loss; in patients receiving antiresorptive therapy annual measurements are probably sufficient.

In patients initiating glucocorticoid therapy, preventive measures must begin at the initiation of glucocorticoid therapy. Bisphosphonates are the antiresorptive agents of choice for the treatment of glucocorticoid-induced osteoporosis, and their effectiveness is supported by controlled clinical trials with increased BMD as the primary end point and reduced fractures as a secondary end point. Alendronate is indicated for treatment of glucocorticoid-induced osteoporosis and risedronate is indicated for both prevention and treatment of this condition. Glucocorticoid-treated premenopausal women, postmenopausal women not receiving HT, and men should be treated with either alendronate 5 mg/d or risedronate 5 mg/d.