Awareness of the need for prevention of glucocorticoid-induced fractures is growing, but glucocorticoid administration is often overlooked as the most common cause of nontraumatic osteonecrosis. Glucocorticoid-induced osteonecrosis develops in 9–40% of patients receiving long-term therapy although it may also occur with short-term exposure to high doses, after intra-articular injection, and without glucocorticoid-induced osteoporosis. The name, osteonecrosis, is misleading because the primary histopathological lesion is osteocyte apoptosis. Apoptotic osteocytes persist because they are anatomically unavailable for phagocytosis and, with glucocorticoid excess, decreased bone remodeling retards their replacement. Glucocorticoid-induced osteocyte apoptosis, a cumulative and unrepairable defect, uniquely disrupts the mechanosensory function of the osteocyte–lacunar–canalicular system and thus starts the inexorable sequence of events leading to collapse of the femoral head. Current evidence indicates that bisphosphonates may rapidly reduce pain, increase ambulation, and delay joint collapse in patients with osteonecrosis.
KeywordsGlucocorticoids Osteonecrosis Avascular necrosis Apoptosis Osteoblasts Osteocytes Bisphosphonates
I am grateful to Drs. Stavros C. Manolagas, Robert L. Jilka, Maria Almeida, and Charles A. O’Brien for their advice and helpful discussions about the adverse skeletal effects of glucocorticoids and for review of the manuscript. This study was supported by VA Merit Review Grants from the Office of Research and Development, Department of Veterans Affairs and the National Institutes of Health (P01-AG13918).
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