Glucocorticoids are one of the most commonly prescribed medications and are used to treat a wide range of chronic inflammatory diseases. The main limitation of this therapy is the development of osteoporosis and bone fractures. Recent studies have given us insight into the epidemiology of glucocorticoid-induced fractures demonstrating both the magnitude of the problem and the types of patients who are likely to be most at risk. Additionally, several randomised trials have demonstrated beneficial effects of bone targeted medications in the setting of glucocorticoid-induced osteoporosis. This article will review these recent findings, will suggest when patients are likely to be at a significant risk of fracture and discuss how best to reduce this risk.
Adachi, J.D. , Bensen, W.G. , Brown, J. , Hanley, D. , Hodsman, A. , Josse, R. et al. (1997) Intermittent etidronate therapy to prevent corticosteroid-induced osteoporosis . N Engl J Med337: 382-387.
2.
American College of Rheumatology Ad Hoc Committee on Glucocorticoid-Induced Osteoporosis (2001) Recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis: 2001 update. American College of Rheumatology Ad Hoc Committee on Glucocorticoid Induced Osteoporosis . Arthritis Rheum44: 1496-1503.
3.
Cohen, S. , Levy, R.M. , Keller, M. , Boling, E. , Emkey, R.D. , Greenwald, M. et al. (1999) Risedronate therapy prevents corticosteroid-induced bone loss: a twelve-month, multicenter, randomized, double-blind, placebo-controlled, parallel-group study . Arthritis Rheum42: 2309-2318.
4.
Compston, J. ( 2002) Glucocorticoid-induced osteoporosis: Guidelines for prevention and treatment, RCP of London: UK.
5.
Cooper, M. ( 2009) Bone protective therapy in the young patient with fractures and chronic disease: what drug(s) should be given and for how long?Clin Endocrinol ( Oxf ) 70: 188-191.
6.
Cooper, M.S. ( 2004) Sensitivity of bone to glucocorticoids . Clinical Science ( London ) 107: 111-123.
7.
Cooper, M.S. , Blumsohn, A. , Goddard, P.E. , Bartlett, W.A. , Shackleton, C.H. , Eastell, R. et al. (2003) 11β-hydroxysteroid dehydrogenase type 1 activity predicts the effects of glucocorticoids on bone . J Clin Endocrinol Metab88: 3874-3877.
8.
Cushing, H.W. ( 1932) The basophil adenomas of the pituitary body and their clinical manifestations (pituitary basophilism) . Bull Johns Hopkins Hosp50: 137-195.
9.
de Nijs, R.N. , Jacobs, J.W. , Lems, W.F. , Laan, R.F. , Algra, A. , Huisman, A.M. et al. (2006) Alendronate or alfacalcidol in glucocorticoid-induced osteoporosis . N Engl J Med355: 675-684.
10.
De, V.F. , Bracke, M. , Leufkens, H.G. , Lammers, J.W. , Cooper, C. and van Staa, T.P. ( 2007) Fracture risk with intermittent high-dose oral glucocorticoid therapy . Arthritis Rheum56: 208-214.
11.
Hardy, R. and Cooper, M.S.(2009) Bone loss in inflammatory disorders . J Endocrinol201: 309-320.
12.
Kanis, J.A. , Johnell, O. , Oden, A. , Johansson, H. and McCloskey, E. ( 2008) FRAX and the assessment of fracture probability in men and women from the UK . Osteoporos Int19: 385-397.
13.
Khosla, S. , Burr, D. , Cauley, J. , Dempster, D.W. , Ebeling, P.R. , Felsenberg, D. et al. (2007) Bisphosphonate-associated osteonecrosis of the jaw: report of a task force of the American Society for Bone and Mineral Research . J Bone Miner Res22: 1479-1491.
14.
Lane, N.E. , Sanchez, S. , Modin, G.W. , Genant, H.K. , ini, E. and Arnaud, C.D. ( 1998) Parathyroid hormone treatment can reverse corticosteroid-induced osteoporosis. Results of a randomized controlled clinical trial . J Clin Invest102: 1627-1633.
15.
Lenart, B.A. , Lorich, D.G. and Lane, J.M. ( 2008) Atypical fractures of the femoral diaphysis in postmenopausal women taking alendronate . N Engl J Med358: 1304-1306.
16.
Leonard, M.B. , Feldman, H.I. , Shults, J. , Zemel, B.S. , Foster, B.J. and Stallings, V.A. ( 2004) Long-term, high-dose glucocorticoids and bone mineral content in childhood glucocorticoid-sensitive nephrotic syndrome . N Engl J Med351: 868-875.
17.
Odvina, C.V. , Zerwekh, J.E. , Rao, D.S. , Maalouf, N. , Gottschalk, F.A. and Pak, C.Y. ( 2005) Severely suppressed bone turnover: a potential complication of alendronate therapy . J Clin Endocrinol Metab90: 1294-1301.
18.
Reginster, J.Y. , Kuntz, D. , Verdickt, W. , Wouters, M. , Guillevin, L. , Menkes, C.J. et al. (1999) Prophylactic use of alfacalcidol in corticosteroid-induced osteoporosis . Osteoporos Int9: 75-81.
19.
Reid, D.M. , Devogelaer, J.P. , Saag, K. , Roux, C. , Lau, C.S. , Reginster, J.Y. et al. (2009) Zoledronic acid and risedronate in the prevention and treatment of glucocorticoid-induced osteoporosis (HORIZON): a multicentre, double-blind, double-dummy, randomised controlled trial . Lancet373: 1253-1263.
20.
Ringe, J.D. , Coster, A. , Meng, T. , Schacht, E. and Umbach, R. ( 1999) Treatment of glucocorticoid-induced osteoporosis with alfacalcidol/calcium versus vitamin D/calcium . Calcif Tissue Int65: 337-340.
21.
Saag, K.G. , Emkey, R. , Schnitzer, T.J. , Brown, J.P. , Hawkins, F. , Goemaere, S. et al. (1998) Alendronate for the prevention and treatment of glucocorticoid-induced osteoporosis. Glucocorticoid-Induced Osteoporosis Intervention Study Group . N Engl J Med339: 292-299.
22.
Saag, K.G. , Shane, E. , Boonen, S. , Marin, F. , Donley, D.W. , Taylor, K.A. et al. (2007) Teriparatide or alendronate in glucocorticoid-induced osteoporosis . N Engl J Med357: 2028-2039.
23.
Sylvester, F.A. , Wyzga, N. , Hyams, J.S. , Davis, P.M. , Lerer, T. , Vance, K. et al. (2007) Natural history of bone metabolism and bone mineral density in children with inflammatory bowel disease . Inflammatory Bowel Disease13: 42-50.
24.
van Staa, T.P. , Leufkens, H.G. , Abenhaim, L. , Begaud, B. , Zhang, B. and Cooper, C. ( 2000a) Use of oral corticosteroids in the United Kingdom . QJM93: 105-111.
25.
van Staa, T.P. , Leufkens, H.G. , Abenhaim, L. , Zhang, B. and Cooper, C. ( 2000b) Use of oral corticosteroids and risk of fractures . J Bone Miner Res15: 993-1000.
26.
van Staa, T.P. , Leufkens, H.G. and Cooper, C.(2001) Use of inhaled corticosteroids and risk of fractures . J Bone Miner Res16: 581-588.
27.
Vestergaard, P. , Rejnmark, L. and Mosekilde, L. ( 2005) Fracture risk associated with systemic and topical corticosteroids . J Intern Med257: 374-384.
28.
Vestergaard, P. , Rejnmark, L. and Mosekilde, L. ( 2008) Fracture risk associated with different types of oral corticosteroids and effect of termination of corticosteroids on the risk of fractures . Calcif Tissue Int82: 249-257.
29.
Weinstein, R.S. , Jilka, R.L. , Parfitt, A.M. and Manolagas, S.C. ( 1998) Inhibition of osteoblastogenesis and promotion of apoptosis of osteoblasts and osteocytes by glucocorticoids. Potential mechanisms of their deleterious effects on bone . J Clin Invest102: 274-282.
30.
Weinstein, R.S. , Nicholas, R.W. and Manolagas, S.C. ( 2000) Apoptosis of osteocytes in glucocorticoid-induced osteonecrosis of the hip . J Clin Endocrinol Metab85: 2907-2912.
31.
Weinstein, R.S. , Wan, C. , Liu, Q. , Wang, Y. , Almeida, M. , O’Brien, C.A. et al. (2009) Endogenous glucocorticoids decrease skeletal angiogenesis, vascularity, hydration, and strength in aged mice . Aging Cell Dec 28 [Epub ahead of print].
