[en] BACKGROUND: We studied 265 men (mean age 56.4years; range 18-83years), among patients enrolled in two arms of a double-blind, 1-year study comparing the effects of zoledronic acid (ZOL) with risedronate (RIS) in patients either commencing (prednisolone 7.5mg/day or equivalent) (prevention arm, n=88) or continuing glucocorticoid therapy (treatment arm, n=177). METHODS: Patients received either a single ZOL 5mg infusion or RIS 5mg oral daily at randomization, along with calcium (1000mg) and vitamin D (400-1200IU). Primary endpoint: difference in percentage change from baseline in bone mineral density (BMD) at the lumbar spine (LS) at 12months. Secondary endpoints: percentage changes in BMD at total hip (TH) and femoral neck (FN), relative changes in bone turnover markers (beta-CTx and P1NP), and overall safety. FINDINGS: In the treatment subpopulation, ZOL increased LS BMD by 4.7% vs. 3.3% for RIS and at TH the percentage changes were 1.8% vs. 0.2%, respectively. In the prevention subpopulation, bone loss was prevented by both treatments. At LS the percentage changes were 2.5% vs. -0.2% for ZOL vs. RIS and at TH the percentage changes were 1.1% vs. -0.4%, respectively. ZOL significantly increased lumbar spine BMD more than RIS at Month 12 in both the prevention population (p=0.0024) and the treatment subpopulation (p=0.0232) in men. In the treatment subpopulation, ZOL demonstrated a significantly greater reduction in serum beta-CTx and P1NP relative to RIS at all time-points. In the prevention subpopulation, ZOL significantly reduced beta-CTx at all time-points, and P1NP at Month 3 (p=0.0297) only. Both treatments were well tolerated in men, albeit with a higher incidence of influenza-like illness and pyrexia events post-infusion with ZOL. INTERPRETATION: Once-yearly ZOL preserves or increases BMD within 1year to a greater extent than daily RIS in men receiving glucocorticoid therapy.
Disciplines :
General & internal medicine
Author, co-author :
Sambrook, P. N.
Roux, C.
Devogelaer, J. P.
Saag, K.
Lau, C. S.
Reginster, Jean-Yves ; Université de Liège - ULiège > Département des sciences de la santé publique > Santé publique, Epidémiologie et Economie de la santé
Bucci-Rechtweg, C.
Su, G.
Reid, D. M.
Language :
English
Title :
Bisphosphonates and glucocorticoid osteoporosis in men: results of a randomized controlled trial comparing zoledronic acid with risedronate.
Publication date :
2012
Journal title :
BONE
ISSN :
8756-3282
eISSN :
1873-2763
Publisher :
Elsevier Science, New York, United States - New York
Civitelli R., Ziambaras K. Epidemiology of glucocorticoid-induced osteoporosis. J Endocrinol Invest 2008, 31(7 Suppl):2-6.
De Nijs R.N. Glucocorticoid-induced osteoporosis: a review on pathophysiology and treatment options. Minerva Med 2008, 99(1):23-43.
McDonough A.K., Curtis J.R., Saag K.G. The epidemiology of glucocorticoid-associated adverse events. Curr Opin Rheumatol 2008, 20(2):131-137.
Canalis E., Mazziotti G., Giustina A., Bilezikian J.P. Glucocorticoid-induced osteoporosis: pathophysiology and therapy. Osteoporos Int 2007, 18(10):1319-1328.
Angeli A., Guglielmi G., Dovio A., et al. High prevalence of asymptomatic vertebral fractures in post-menopausal women receiving chronic glucocorticoid therapy: a cross-sectional outpatient study. Bone 2006, 39(2):253-259.
Devogelaer J.P. Glucocorticoid-induced osteoporosis: mechanisms and therapeutic approach. Rheum Dis Clin North Am 2006, 32(4):733-757.
Devogelaer J.P., Goemaere S., Boonen S., et al. Evidence-based guidelines for the prevention and treatment of glucocorticoid-induced osteoporosis: a consensus document of the Belgian Bone Club. Osteoporos Int 2006, 17(1):8-19.
Van Staa T.P. The pathogenesis, epidemiology and management of glucocorticoid-induced osteoporosis. Calcif Tissue Int 2006, 79(3):129-137.
Van Staa T.P., Leufkens H.G., Cooper C. The epidemiology of corticosteroid-induced osteoporosis: a meta-analysis. Osteoporos Int 2002, 13(10):777-787.
Adler R.A., Hochberg M.C. Suggested guidelines for evaluation and treatment of glucocorticoid-induced osteoporosis for the Department of Veterans Affairs. Arch Intern Med 2003, 163(21):2619-2624.
Compston J. Management of glucocorticoid-induced osteoporosis. Nat Rev Rheumatol 2010, 6(2):82-88.
Adachi J.D., Papaioannou A. In whom and how to prevent glucocorticoid-induced osteoporosis. Best Pract Res Clin Rheumatol 2005, 19(6):1039-1064.
Boling E.P. Secondary osteoporosis: underlying disease and the risk for glucocorticoid-induced osteoporosis. Clin Ther 2004, 26(1):1-14.
American CoRAHCoG-IO 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(7):1496-1503.
Sambrook P.N., Eisman J.A., Champion G.D., Pocock N.A. Sex hormone status and osteoporosis in postmenopausal women with rheumatoid arthritis. Arthritis Rheum 1988, 31(8):973-978.
Plotkin L.I., Manolagas S.C., Bellido T. Dissociation of the pro-apoptotic effects of bisphosphonates on osteoclasts from their anti-apoptotic effects on osteoblasts/osteocytes with novel analogs. Bone 2006, 39(3):443-452.
Weinstein R.S., Chen J.R., Powers C.C., et al. Promotion of osteoclast survival and antagonism of bisphosphonate-induced osteoclast apoptosis by glucocorticoids. J Clin Invest 2002, 109(8):1041-1048.
Miller P.D. Anti-resorptives in the management of osteoporosis. Best Pract Res Clin Endocrinol Metab 2008, 22(5):849-868.
Saag K.G., Emkey R., Schnitzer T.J., et al. Alendronate for the prevention and treatment of glucocorticoid-induced osteoporosis. Glucocorticoid-Induced Osteoporosis Intervention Study Group. N Engl J Med 1998, 339(5):292-299.
Reid D.M., Hughes R.A., Laan R.F., 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(6):1006-1013.
Cohen S., Levy R.M., 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(11):2309-2318.
Roux C., Oriente P., Laan R., et al. Randomized trial of effect of cyclical etidronate in the prevention of corticosteroid-induced bone loss. Ciblos Study Group. J Clin Endocrinol Metab 1998, 83(4):1128-1133.
Adachi J.D., Saag K.G., Delmas P.D., 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(1):202-211.
Wallach S., Cohen S., Reid D.M., et al. Effects of risedronate treatment on bone density and vertebral fracture in patients on corticosteroid therapy. Calcif Tissue Int 2000, 67(4):277-285.
Adachi J.D., Bensen W.G., Brown J., et al. Intermittent etidronate therapy to prevent corticosteroid-induced osteoporosis. N Engl J Med 1997, 337(6):382-387.
Stoch S.A., Saag K.G., 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(8):1705-1714.
Ringe J.D., Dorst A., Faber H., Ibach K., Sorenson F. Intermittent intravenous ibandronate injections reduce vertebral fracture risk in corticosteroid-induced osteoporosis: results from a long-term comparative study. Osteoporos Int 2003, 14(10):801-807.
Saag K.G., Shane E., Boonen S., et al. Teriparatide or alendronate in glucocorticoid-induced osteoporosis. N Engl J Med 2007, 357(20):2028-2039.
Compston J., Reid D.M., Boisdron J., et al. Recommendations for the registration of agents for prevention and treatment of glucocorticoid-induced osteoporosis: an update from the Group for the Respect of Ethics and Excellence in Science. Osteoporos Int 2008, 19(9):1247-1250.
Reid D.M., Adami S., Devogelaer J.P., Chines A.A. Risedronate increases bone density and reduces vertebral fracture risk within one year in men on corticosteroid therapy. Calcif Tissue Int 2001, 69(4):242-247.
Reid D.M. Corticosteroid-induced osteoporosis: guidelines for prevention-are they useful?. Br J Rheumatol 1997, 36(10):1035-1037.
Reid I.R., Wattie D.J., Evans M.C., Stapleton J.P. Testosterone therapy in glucocorticoid-treated men. Arch Intern Med 1996, 156(11):1173-1177.
Reid D.M., Devogelaer J.P., 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(9671):1253-1263.
Genant H.K., van Kuiik C., Nevitt M.C. Vertebral fracture assessment using a semiquantitative technique. J Bone Miner Res 1993, 8(9):1137-1148.
Russell R.G., Watts N.B., Ebetino F.H., Rogers M.J. Mechanisms of action of bisphosphonates: similarities and differences and their potential influence on clinical efficacy. Osteoporos Int 2008, 19(6):733-759.
Nordin B.E.C., Marshall D.H., Francis R.M., Grillyy R.G. The effects of sex steroid and corticosteroid hormones on bone. J Steroid Biochem 1981, 15:171-174.
Katznelson L., Finkelstein J.S., Schoenfeld D.A., Rosenthal D.I., Anderson E.J., Klibanski A. Increase in bone density and lean body mass during testosterone administration in men with acquired hypogonadism. J Clin Endocrinol Metab 1996, 81:4358-4365.
Reid I.R., France J.T., Pybus J., Ibbertson H.K. Low plasma testosterone levels in glucocorticoid-treated male asthmatics. Br Med J (Clin Res Ed) 1985, 291:574-578.
Roux C, Reid D, Saag K, Lau CS, Reginster JY, Papanastiuo P, Si G, Bucci-Rechtwag C, Sambrook PN. Post hoc analysis of a single IV infusion of zoledronic acid vs daily risedronate on lumbar spine bone mineral density in different subgroup with glucocorticoid induced osteoporosis. Osteoporos Int in press.
Adachi J.D., Saag K.G., Delmas P.D., 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(1):202-211.