Skeletal diseases in Cushing's syndrome: osteoporosis versus arthropathy

Structural and functional impairment of the skeletal system remains an important cause of morbidity and disability in patients with Cushing's syndrome (CS). Glucocorticoid (GC) excess inhibits bone formation and calcium absorption from the gut, increases bone resorption, and alters the secretion of gonadotropin and growth hormones, cytokines and growth factors influencing bone. Both overt and subtle endogenous hypercortisolism affect bone, leading to vertebral fractures in up to 70% of patients. Fracture risk is related to age at onset, duration and severity of the disease and individual susceptibility to GCs that is genetically determined. Bone mineral density (BMD) measurement at the lumbar spine should be performed as a screening test in all patients with CS due to the preferential loss of trabecular bone induced by GCs. The higher risk of fractures at comparable BMD values with controls suggests that bone quality features, not assessed by routine BMD approaches, are also important and should be addressed when indicated applying specific radiological means. Successful treatment of GC excess is associated with improvement in bone mass which, although delayed and often incomplete, reduces the risk of osteoporotic fractures. Bisphosphonates can induce a more rapid improvement in BMD than cortisol normalization alone and can be used in patients with increased risks for further fractures and/or persistent hypercortisolemia to prevent further bone loss. Anabolic agents have not as yet been systemically used. Avascular necrosis, mainly of the femoral neck, and growth arrest in children are the most common skeletal disorders unrelated to osteoporosis encountered in patients with endogenous hypercortisolism.