Prevention and treatment of glucocorticoid-induced osteoporosis
- Harold N Rosen, MD
Harold N Rosen, MD
- Assistant Professor in Medicine
- Harvard Medical School
- Kenneth G Saag, MD, MSc
Kenneth G Saag, MD, MSc
- Professor of Medicine
- University of Alabama at Birmingham
Glucocorticoid therapy is associated with an appreciable risk of bone loss, which is most pronounced in the first few months of use. In addition, glucocorticoids increase fracture risk, and fractures occur at higher bone mineral density (BMD) values than occur in postmenopausal osteoporosis. The increased risk of fracture has been reported with doses of prednisone or its equivalent as low as 2.5 to 7.5 mg daily . Thus, glucocorticoid-induced bone loss should be treated aggressively, particularly in those already at high risk for fracture (older, prior fragility fracture). In other individuals, clinical risk factor and bone density assessment may help guide therapy. The prevention and treatment of glucocorticoid-induced bone loss will be reviewed here. The clinical features are reviewed separately. (See "Pathogenesis, clinical features, and evaluation of glucocorticoid-induced osteoporosis".)
Many of the prevention and treatment strategies for glucocorticoid-induced bone loss are similar to those used to prevent and treat other causes of osteoporosis. (See "Overview of the management of osteoporosis in postmenopausal women" and "Treatment of osteoporosis in men" and "Evaluation and treatment of premenopausal osteoporosis".)
Prevention and treatment strategies consist of attempts to reverse the glucocorticoid excess by decreasing the dose of exogenous glucocorticoid or curing the cause of endogenous cortisol overproduction, calcium and vitamin D supplementation, and in some patients, pharmacologic therapy to minimize further bone loss or reverse it. In an attempt to minimize bone loss, certain general principles should be followed in all patients receiving all doses of glucocorticoids for a duration of ≥3 months [2,3].
●The glucocorticoid dose and the duration of therapy should be as low as possible, because even what are thought to be replacement doses or chronic inhaled glucocorticoids can cause bone loss . Alternative therapy should be used whenever possible. (See "Major side effects of inhaled glucocorticoids", section on 'Osteoporosis'.)
●When glucocorticoids are given, topical therapy (such as inhaled glucocorticoids or glucocorticoid enemas for asthma or bowel disease, respectively) is preferred over enteral or parenteral glucocorticoids, whenever possible.
- van Staa TP, Leufkens HG, Cooper C. The epidemiology of corticosteroid-induced osteoporosis: a meta-analysis. Osteoporos Int 2002; 13:777.
- Heffernan MP, Saag KG, Robinson JK, Callen JP. Prevention of osteoporosis associated with chronic glucocorticoid therapy. JAMA 2006; 295:1300.
- Grossman JM, Gordon R, Ranganath VK, et al. American College of Rheumatology 2010 recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis. Arthritis Care Res (Hoboken) 2010; 62:1515.
- Zelissen PM, Croughs RJ, van Rijk PP, Raymakers JA. Effect of glucocorticoid replacement therapy on bone mineral density in patients with Addison disease. Ann Intern Med 1994; 120:207.
- Reid DM, Nicoll JJ, Smith MA, et al. Corticosteroids and bone mass in asthma: comparisons with rheumatoid arthritis and polymyalgia rheumatica. Br Med J (Clin Res Ed) 1986; 293:1463.
- Wang WQ, Ip MS, Tsang KW, Lam KS. Antiresorptive therapy in asthmatic patients receiving high-dose inhaled steroids: a prospective study for 18 months. J Allergy Clin Immunol 1998; 101:445.
- Homik J, Suarez-Almazor ME, Shea B, et al. Calcium and vitamin D for corticosteroid-induced osteoporosis. Cochrane Database Syst Rev 2000; :CD000952.
- Buckley LM, Leib ES, Cartularo KS, et al. Calcium and vitamin D3 supplementation prevents bone loss in the spine secondary to low-dose corticosteroids in patients with rheumatoid arthritis. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 1996; 125:961.
- Boutsen Y, Jamart J, Esselinckx W, Devogelaer JP. Primary prevention of glucocorticoid-induced osteoporosis with intravenous pamidronate and calcium: a prospective controlled 1-year study comparing a single infusion, an infusion given once every 3 months, and calcium alone. J Bone Miner Res 2001; 16:104.
- Sambrook P, Birmingham J, Kelly P, et al. Prevention of corticosteroid osteoporosis. A comparison of calcium, calcitriol, and calcitonin. N Engl J Med 1993; 328:1747.
- Cohen S, Levy RM, Keller M, et al. Risedronate therapy prevents corticosteroid-induced bone loss: a twelve-month, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Arthritis Rheum 1999; 42:2309.
- Saag KG, Emkey R, Schnitzer TJ, et al. Alendronate for the prevention and treatment of glucocorticoid-induced osteoporosis. Glucocorticoid-Induced Osteoporosis Intervention Study Group. N Engl J Med 1998; 339:292.
- Recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis: 2001 update. American College of Rheumatology Ad Hoc Committee on Glucocorticoid-Induced Osteoporosis. Arthritis Rheum 2001; 44:1496.
- Lukert BP, Raisz LG. Glucocorticoid-induced osteoporosis: pathogenesis and management. Ann Intern Med 1990; 112:352.
- Richy F, Ethgen O, Bruyere O, Reginster JY. Efficacy of alphacalcidol and calcitriol in primary and corticosteroid-induced osteoporosis: a meta-analysis of their effects on bone mineral density and fracture rate. Osteoporos Int 2004; 15:301.
- Suzuki Y, Ichikawa Y, Saito E, Homma M. Importance of increased urinary calcium excretion in the development of secondary hyperparathyroidism of patients under glucocorticoid therapy. Metabolism 1983; 32:151.
- Sambrook PN, Kotowicz M, Nash P, et al. Prevention and treatment of glucocorticoid-induced osteoporosis: a comparison of calcitriol, vitamin D plus calcium, and alendronate plus calcium. J Bone Miner Res 2003; 18:919.
- de Nijs RN, Jacobs JW, Lems WF, et al. Alendronate or alfacalcidol in glucocorticoid-induced osteoporosis. N Engl J Med 2006; 355:675.
- Homik J, Cranney A, Shea B, et al. Bisphosphonates for steroid induced osteoporosis. Cochrane Database Syst Rev 2000; :CD001347.
- Saag KG, Shane E, Boonen S, et al. Teriparatide or alendronate in glucocorticoid-induced osteoporosis. N Engl J Med 2007; 357:2028.
- MacLean C, Newberry S, Maglione M, et al. Systematic review: comparative effectiveness of treatments to prevent fractures in men and women with low bone density or osteoporosis. Ann Intern Med 2008; 148:197.
- Langdahl BL, Marin F, Shane E, et al. Teriparatide versus alendronate for treating glucocorticoid-induced osteoporosis: an analysis by gender and menopausal status. Osteoporos Int 2009; 20:2095.
- Adachi JD, Bensen WG, Brown J, et al. Intermittent etidronate therapy to prevent corticosteroid-induced osteoporosis. N Engl J Med 1997; 337:382.
- Plotkin LI, Weinstein RS, Parfitt AM, et al. Prevention of osteocyte and osteoblast apoptosis by bisphosphonates and calcitonin. J Clin Invest 1999; 104:1363.
- Weinstein RS, Chen JR, Powers CC, et al. Promotion of osteoclast survival and antagonism of bisphosphonate-induced osteoclast apoptosis by glucocorticoids. J Clin Invest 2002; 109:1041.
- Adachi JD, Saag KG, Delmas PD, et al. Two-year effects of alendronate on bone mineral density and vertebral fracture in patients receiving glucocorticoids: a randomized, double-blind, placebo-controlled extension trial. Arthritis Rheum 2001; 44:202.
- Stoch SA, Saag KG, Greenwald M, et al. Once-weekly oral alendronate 70 mg in patients with glucocorticoid-induced bone loss: a 12-month randomized, placebo-controlled clinical trial. J Rheumatol 2009; 36:1705.
- Reid DM, Hughes RA, Laan RF, et al. Efficacy and safety of daily risedronate in the treatment of corticosteroid-induced osteoporosis in men and women: a randomized trial. European Corticosteroid-Induced Osteoporosis Treatment Study. J Bone Miner Res 2000; 15:1006.
- Eastell R, Devogelaer JP, Peel NF, et al. Prevention of bone loss with risedronate in glucocorticoid-treated rheumatoid arthritis patients. Osteoporos Int 2000; 11:331.
- Reid DM, Devogelaer JP, Saag K, et al. Zoledronic acid and risedronate in the prevention and treatment of glucocorticoid-induced osteoporosis (HORIZON): a multicentre, double-blind, double-dummy, randomised controlled trial. Lancet 2009; 373:1253.
- Reid IR, King AR, Alexander CJ, Ibbertson HK. Prevention of steroid-induced osteoporosis with (3-amino-1-hydroxypropylidene)-1,1-bisphosphonate (APD). Lancet 1988; 1:143.
- Reid IR, Heap SW, King AR, Ibbertson HK. Two-year follow-up of biphosphonate (APD) treatment in steroid osteoporosis. Lancet 1988; 2:1144.
- Gallacher SJ, Fenner JA, Anderson K, et al. Intravenous pamidronate in the treatment of osteoporosis associated with corticosteroid dependent lung disease: an open pilot study. Thorax 1992; 47:932.
- Ringe JD, Dorst A, Faber H, et al. Three-monthly ibandronate bolus injection offers favourable tolerability and sustained efficacy advantage over two years in established corticosteroid-induced osteoporosis. Rheumatology (Oxford) 2003; 42:743.
- Ringe JD, Dorst A, Faber H, et al. Intermittent intravenous ibandronate injections reduce vertebral fracture risk in corticosteroid-induced osteoporosis: results from a long-term comparative study. Osteoporos Int 2003; 14:801.
- Kikuchi Y, Imakiire T, Yamada M, et al. Effect of risedronate on high-dose corticosteroid-induced bone loss in patients with glomerular disease. Nephrol Dial Transplant 2007; 22:1593.
- Fujii N, Hamano T, Mikami S, et al. Risedronate, an effective treatment for glucocorticoid-induced bone loss in CKD patients with or without concomitant active vitamin D (PRIUS-CKD). Nephrol Dial Transplant 2007; 22:1601.
- Carpinteri R, Porcelli T, Mejia C, et al. Glucocorticoid-induced osteoporosis and parathyroid hormone. J Endocrinol Invest 2010; 33:16.
- Saag KG, Zanchetta JR, Devogelaer JP, et al. Effects of teriparatide versus alendronate for treating glucocorticoid-induced osteoporosis: thirty-six-month results of a randomized, double-blind, controlled trial. Arthritis Rheum 2009; 60:3346.
- Lane NE, Sanchez S, Modin GW, et al. Parathyroid hormone treatment can reverse corticosteroid-induced osteoporosis. Results of a randomized controlled clinical trial. J Clin Invest 1998; 102:1627.
- Glüer CC, Marin F, Ringe JD, et al. Comparative effects of teriparatide and risedronate in glucocorticoid-induced osteoporosis in men: 18-month results of the EuroGIOPs trial. J Bone Miner Res 2013; 28:1355.
- MacAdams MR, White RH, Chipps BE. Reduction of serum testosterone levels during chronic glucocorticoid therapy. Ann Intern Med 1986; 104:648.
- Laatikainen AK, Kröger HP, Tukiainen HO, et al. Bone mineral density in perimenopausal women with asthma: a population-based cross-sectional study. Am J Respir Crit Care Med 1999; 159:1179.
- Reid IR, Wattie DJ, Evans MC, Stapleton JP. Testosterone therapy in glucocorticoid-treated men. Arch Intern Med 1996; 156:1173.
- Crawford BA, Liu PY, Kean MT, et al. Randomized placebo-controlled trial of androgen effects on muscle and bone in men requiring long-term systemic glucocorticoid treatment. J Clin Endocrinol Metab 2003; 88:3167.
- Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. JAMA 2002; 288:321.
- Luengo M, Pons F, Martinez de Osaba MJ, Picado C. Prevention of further bone mass loss by nasal calcitonin in patients on long term glucocorticoid therapy for asthma: a two year follow up study. Thorax 1994; 49:1099.
- Montemurro L, Schiraldi G, Fraioli P, et al. Prevention of corticosteroid-induced osteoporosis with salmon calcitonin in sarcoid patients. Calcif Tissue Int 1991; 49:71.
- Cranney, A, Welch, V, Adachi, J, et al. Calcitonin for preventing and treating corticosteroid-induced osteoporosis. Cochrane Database of Systematic Reviews 2000; CD001983.
- Hofbauer LC, Zeitz U, Schoppet M, et al. Prevention of glucocorticoid-induced bone loss in mice by inhibition of RANKL. Arthritis Rheum 2009; 60:1427.
- Dore RK, Cohen SB, Lane NE, et al. Effects of denosumab on bone mineral density and bone turnover in patients with rheumatoid arthritis receiving concurrent glucocorticoids or bisphosphonates. Ann Rheum Dis 2010; 69:872.
- Hermus AR, Smals AG, Swinkels LM, et al. Bone mineral density and bone turnover before and after surgical cure of Cushing's syndrome. J Clin Endocrinol Metab 1995; 80:2859.
- Pocock NA, Eisman JA, Dunstan CR, et al. Recovery from steroid-induced osteoporosis. Ann Intern Med 1987; 107:319.
- http://mail3.rheumatology.org/practice/clinical/guidelines/ACR_2010_GIOP_Recomm_Clinicians_Guide.pdf (Accessed on January 14, 2011).
- Royal College of Physicians, 2002 Glucocorticoid-induced osteoporosis: A concise guide to prevention and treatment. http://bookshop.rcplondon.ac.uk/contents/pub89-64206b70-b147-4976-9ee1-bf4948458468.pdf (Accessed on May 06, 2013).
- Lekamwasam S, Adachi JD, Agnusdei D, et al. A framework for the development of guidelines for the management of glucocorticoid-induced osteoporosis. Osteoporos Int 2012; 23:2257.
- GENERAL MEASURES
- CALCIUM AND VITAMIN D
- Active vitamin D metabolites
- CANDIDATES FOR PHARMACOLOGIC THERAPY
- Osteoporosis prevention
- Established osteoporosis
- Premenopausal women and younger men
- CHOICE OF THERAPY
- Zoledronic acid
- Other bisphosphonates
- Bisphosphonates versus active D metabolites
- PARATHYROID HORMONE
- HORMONE REPLACEMENT
- Effect of cessation of glucocorticoid therapy
- SOCIETY GUIDELINE LINKS
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS