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.

1.
Chiodini I, Torlontano M, Carnevale V, Trischitta V, Scillitani A: Skeletal involvement in adult patients with endogenous hypercortisolism. J Endocrinol Invest 2008;31:267–276.
2.
Mazziotti G, Angeli A, Bilezikian JP, Canalis E, Giustina A: Glucocorticoid-induced osteoporosis: an update. Trends Endocrinol Metab 2006;17:144–149.
3.
Manelli F, Giustina A: Glucocorticoid-induced osteoporosis. Trends Endocrinol Metab 2000;11:79–85.
4.
Karavitaki N, Ioannidis G, Giannakopoulos F, Mavrokefalos P, Thalassinos N: Evaluation of bone mineral density of the peripheral skeleton in pre- and postmenopausal women with newly diagnosed endogenous Cushing’s syndrome. Clin Endocrinol (Oxf) 2004;60:264–270.
5.
Mancini T, Doga M, Mazziotti G, Giustina A: Cushing’s syndrome and bone. Pituitary 2004;7:249–252.
6.
Canalis E: Mechanisms of glucocorticoid action in bone. Curr Osteoporos Rep 2005;3:98–102.
7.
Manolagas SC: Corticosteroids and fractures: a close encounter of the third cell kind. J Bone Miner Res 2000;15:1001–1005.
8.
Lekva T, Bollerslev J, Kristo C, Olstad OK, Ueland T, Jemtland R: The glucocorticoid-induced leucine zipper gene (GILZ) expression decreases after successful treatment of patients with endogenous Cushing’s syndrome and may play a role in glucocorticoid-induced osteoporosis. J Clin Endocrinol Metab 2010;95:246–255.
9.
Shaker JL, Lukert BP: Osteoporosis associated with excess glucocorticoids. Endocrinol Metab Clin North Am 2005;34:341–343ix.
10.
Tauchmanovà L, Pivonello R, Di SC, Rossi R, De Martino MC, Camera L, Klain M, Salvatore M, Lombardi G, Colao A: Bone demineralization and vertebral fractures in endogenous cortisol excess: role of disease etiology and gonadal status. J Clin Endocrinol Metab 2006;91:1779–1784.
11.
Vestergaard P, Lindholm J, Jorgensen JO, Hagen C, Hoeck HC, Laurberg P, Rejnmark L, Brixen K, Kristensen LO, Feldt-Rasmussen U, Mosekilde L: Increased risk of osteoporotic fractures in patients with Cushing’s syndrome. Eur J Endocrinol 2002;146:51–56.
12.
Torlontano M, Chiodini I, Pileri M, Guglielmi G, Cammisa M, Modoni S, Carnevale V, Trischitta V, Scillitani A: Altered bone mass and turnover in female patients with adrenal incidentaloma: the effect of subclinical hypercortisolism. J Clin Endocrinol Metab 1999;84:2381–2385.
13.
Huizenga NA, Koper JW, De Lange P, Pols HA, Stolk RP, Burger H, Grobbee DE, Brinkmann AO, De Jong FH, Lamberts SW: A polymorphism in the glucocorticoid receptor gene may be associated with and increased sensitivity to glucocorticoids in vivo. J Clin Endocrinol Metab 1998;83:144–151.
14.
Tomlinson JW, Walker EA, Bujalska IJ, Draper N, Lavery GG, Cooper MS, Hewison M, Stewart PM: 11beta-hydroxysteroid dehydrogenase type 1: a tissue-specific regulator of glucocorticoid response. Endocr Rev 2004;25:831–866.
15.
Osella G, Terzolo M, Reimondo G, Piovesan A, Pia A, Termine A, Paccotti P, Angeli A: Serum markers of bone and collagen turnover in patients with Cushing’s syndrome and in subjects with adrenal incidentalomas. J Clin Endocrinol Metab 1997;82:3303–3307.
16.
Kaji H, Yamauchi M, Chihara K, Sugimoto T: Glucocorticoid excess affects cortical bone geometry in premenopausal, but not postmenopausal, women. Calcif Tissue Int 2008;82:182–190.
17.
Tauchmanovà L, Pivonello R, De Martino MC, Rusciano A, De LM, Ruosi C, Mainolfi C, Lombardi G, Salvatore M, Colao A: Effects of sex steroids on bone in women with subclinical or overt endogenous hypercortisolism. Eur J Endocrinol 2007;157:359–366.
18.
Cummings SR, San MJ, McClung MR, Siris ES, Eastell R, Reid IR, Delmas P, Zoog HB, Austin M, Wang A, Kutilek S, Adami S, Zanchetta J, Libanati C, Siddhanti S, Christiansen C: Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med 2009;361:756–765.
19.
Adachi JD, Papaioannou A: Corticosteroid-Induced osteoporosis: detection and management. Drug Saf 2001;24:607–624.
20.
Adachi JD: Corticosteroid-induced osteoporosis. Am J Med Sci 1997;313:41–49.
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