Efficacy and Safety of Bisphosphonates for Glucocorticoid Induced Osteoporosis: A Systematic Review_Chinese Journal of Evidence-Based Medicine

Authors：

 ZHAOHong-wei ^1,2 ,  ZHANGChao ¹ , QIUTing-ting ^1,3

1. Department of Pharmacy, Peking University Third Hospital, Beijing 100191, China;
2. Department of Pharmacy, Peking University First Hospital-Miyun Hospital, Beijing 101500, China;
3. School of basic medicine and clinical pharmacy, China Pharmaceutical University, Nanjing 211198, China;

Corresponding?author：

ZHANGChao, Email: laural.zhang@yahoo.com

Keywords：

Glucocorticoid; Osteoporosis; Bisphosphonates; Systematic review; Meta-analysis

DOI：

10.7507/1672-2531.20160215

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Objective To evaluate the efficacy and safety of bisphosphonates in preventing and treating glucocorticoid induced osteoporosis. Methods Databases including PubMed, EMbase, The Cochrane Library (Issue 1, 2016), CNKI, WanFang Data and VIP were searched to collect randomized controlled trials (RCTs) related bisphosphonates for the prevention and treatment of glucocorticoid induced osteoporosis from inception to January 2016. Two reviewers independently screened literature, extracted data, and evaluated the risk of bias of included studies. Meta-analysis was performed using RevMan 5.3 software. Results A total of 20 RCTs were included, which involved 2 330 patients. The results of meta-analysis showed that, compared with the placebo group, the bisphosphonates group could significantly increase the bone mineral density (BMD) at lumbar and femoral neck (MD=3.70, 95%CI 2.65 to 4.75, P<0.000 01; MD=2.18, 95%CI 1.30 to 3.06, P<0.000 01), but the bisphosphonates group could not decrease the incidence rates of vertebral fracture or non-vertebral fracture (OR=0.66, 95%CI 0.38 to 1.16, P=0.15; OR=0.73, 95%CI 0.42 to 1.28, P=0.28). There were no significant differences in the incidence rates of total adverse reactions and total severe adverse reactions between the two groups (OR=0.89, 95%CI 0.62 to 1.28, P=0.53; OR=0.93, 95%CI 0.62 to 1.39, P=0.72). Conclusion Current evidence shows that, compared with placebo, bisphosphonates canld effectively prevent and treat the decrease of bone mineral density of glucocorticoid induced osteoporosis, not decrease the incidence of fracture, but not increase the incidence of adverse reactions.

Citation： ZHAOHong-wei, ZHANGChao, QIUTing-ting. Efficacy and Safety of Bisphosphonates for Glucocorticoid Induced Osteoporosis: A Systematic Review. Chinese Journal of Evidence-Based Medicine, 2016, 16(12): 1423-1433. doi: 10.7507/1672-2531.20160215 Copy

1.	Boling EP. Secondary osteoporosis:underlying disease and the risk for glucocorticoid-induced osteoporosis. Clin Ther, 2004, 26(1):1-14.
2.	張冬燕, 趙紅衛, 秦玉花. 糖皮質激素性骨質疏松癥的案例分析. 中國臨床藥理學雜志, 2016, 32(4):358-359.
3.	Guo Z, Wu R, Gong J, et al. The efficacy and safety of bisphosphonates for osteoporosis or osteopenia in Crohn's disease:a meta-analysis. Dig Dis Sci, 2013, 58(4):915-922.
4.	American College of Rheumatology Ad Hoc Committee on Glucocorticoid-Induced Osteoporosis. Recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis:2001 update. Arthritis Rheum, 2001, 44(7):1496-1503.
5.	巴建明. 二膦酸鹽治療骨質疏松進展. 中華醫學會第十一次全國內分泌學學術會議論文匯編. 2012.
6.	田艷平, 朱燕. 雙膦酸鹽不良反應30例文獻分析. 中國藥業, 2012, 21(15):69-70.
7.	Higgins JP, Altman DG, G?tzsche PC, et al. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ, 2011, 343:d5928.
8.	Hakala M, Kr?ger H, Valleala H, et al. Once-monthly oral ibandronate provides significant improvement in bone mineral density in postmenopausal women treated with glucocorticoids for inflammatory rheumatic diseases:a 12-month, randomized, double-blind, placebo-controlled trial. Scand J Rheumatol, 2012, 41(4):260-266.
9.	Tee SI, Yosipovitch G, Chan YC, et al. Prevention of glucocorticoid-induced osteoporosis in immunobullous diseases with alendronate:a randomized, double-blind, placebo-controlled study. Arch Dermatol, 2012, 148(3):307-314.
10.	Li EK, Zhu TY, Hung VY, et al. Ibandronate increases cortical bone density in patients with systemic lupus erythematosus on long-term glucocorticoid. Arthritis Res Ther, 2010, 12(5):1-8.
11.	Takei T, Itabashi M, Tsukada M, et al. Risedronate therapy for the prevention of steroid-induced osteoporosis in patients with minimal-change nephrotic syndrome. Inter Med, 2010, 49(19):2065-2070.
12.	Stoch SA, Saag KG, Greenwald M. 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.
13.	Yeap SS, Fauzi AR, Kong NC, et al. A comparison of calcium, calcitriol, and alendronate in corticosteroid-treated premenopausal patients with systemic lupus erythematosus. J Rheumatol, 2008, 35(35):2344-2347.
14.	Okada Y, Nawata M, Nakayamada S, et al. Alendronate protects premenopausal women from bone loss and fracture associated with high-dose glucocorticoid therapy. J Rheumatol, 2008, 35(11):2249-2254.
15.	Lems WF, Lodder MC, Lips P, et al. Positive effect of alendronate on bone mineral density and markers of bone turnover in patients with rheumatoid arthritis on chronic treatment with low-dose prednisone:a randomized, double-blind, placebo-controlled trial. Osteoporos Int, 2006, 17(5):716-723.
16.	Boutsen Y, Jamart J, Esselinckx W, et al. 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(1):104-112.
17.	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 Rheumatol, 2001, 44(1):202-211.
18.	Lau EM, Woo J, Chan YH, et al. Alendronate for the prevention of bone loss in patients on inhaled steroid therapy. Bone, 2001, 29(6):506-510.
19.	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(6):1006-1013.
20.	Jenkins EA, Walker-Bone KE, Wood A, et al. The prevention of corticosteroid-induced bone loss with intermittent cyclical etidronate. Scand J Rheumatol, 1999, 28(3):152-156.
21.	Geusens P, Dequeker J, Vanhoof J, et al. Cyclical etidronate increases bone density in the spine and hip of postmenopausal women receiving long term corticosteroid treatment. A double blind, randomised placebo controlled study. Ann Rheum Dis, 1998, 57(12):724-727.
22.	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.
23.	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(5):292-299.
24.	Adachi JD, Bensen WG, Brown J, et al. Intermittent etidronate therapy to prevent corticosteroid-induced osteoporosis. N Engl J Med, 1997, 337(6):382-387.
25.	楊雪驊, 陳志君, 左權, 等. 阿侖膦酸鈉、阿法骨化醇、碳酸鈣聯合應用治療糖皮質激素誘發的骨質疏松癥32例療效分析. 上海醫藥, 2014, (1):28-31.
26.	程勇軍, 王文龍, 李云生, 等. 阿侖膦酸鈉治療糖皮質激素依賴的腎病綜合征研究. 中華全科醫學, 2014, 12(3):365-367.
27.	張啟祥, 孔建平. 利塞膦酸鈉對糖皮質激素誘導的骨質疏松的療效觀察. 中國現代應用藥學, 2011, (6):585-588.
28.	全會標, 高勇義. 利塞膦酸鈉臨床研究進展. 醫學綜述, 2007, 13(1):66-68.
29.	Lanza FL, Hunt RH, Thomson AB, et al. Endoscopic comparison of esophageal and gastroduodenal effects of risedronate and alendronate in postmenopausal women. Gastroenterology, 2000, 119(3):631-638.
30.	Lekamwasam S, Adachi J D, Agnusdei D, et al. A framework for the development of guidelines for the management of glucocorticoid-induced osteoporosis. N Engl J Med, 2012, 23(9):2257-2276.
31.	de Nijs RN, Jacobs JW, Lems WF, et al. Alendronate or alfacalcidol in glucocorticoid-induced osteoporosis. N Engl J Med, 2006, 355(7):675-684.
32.	Thomas T, Horlait S, Ringe JD, et al. Oral bisphosphonates reduce the risk of clinical fractures in glucocorticoid-induced osteoporosis in clinical practice. Osteoporos Int, 2013, 24(1):263-269.
33.	楊琳, 田金徽, 何智余, 等. 阿侖膦酸鈉對糖皮質激素導致骨質疏松防治作用的Meta分析. 中華內科雜志, 2013, 52(10):838-843.

1. Boling EP. Secondary osteoporosis:underlying disease and the risk for glucocorticoid-induced osteoporosis. Clin Ther, 2004, 26(1):1-14.
2. 張冬燕, 趙紅衛, 秦玉花. 糖皮質激素性骨質疏松癥的案例分析. 中國臨床藥理學雜志, 2016, 32(4):358-359.
3. Guo Z, Wu R, Gong J, et al. The efficacy and safety of bisphosphonates for osteoporosis or osteopenia in Crohn's disease:a meta-analysis. Dig Dis Sci, 2013, 58(4):915-922.
4. American College of Rheumatology Ad Hoc Committee on Glucocorticoid-Induced Osteoporosis. Recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis:2001 update. Arthritis Rheum, 2001, 44(7):1496-1503.
5. 巴建明. 二膦酸鹽治療骨質疏松進展. 中華醫學會第十一次全國內分泌學學術會議論文匯編. 2012.
6. 田艷平, 朱燕. 雙膦酸鹽不良反應30例文獻分析. 中國藥業, 2012, 21(15):69-70.
7. Higgins JP, Altman DG, G?tzsche PC, et al. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ, 2011, 343:d5928.
8. Hakala M, Kr?ger H, Valleala H, et al. Once-monthly oral ibandronate provides significant improvement in bone mineral density in postmenopausal women treated with glucocorticoids for inflammatory rheumatic diseases:a 12-month, randomized, double-blind, placebo-controlled trial. Scand J Rheumatol, 2012, 41(4):260-266.
9. Tee SI, Yosipovitch G, Chan YC, et al. Prevention of glucocorticoid-induced osteoporosis in immunobullous diseases with alendronate:a randomized, double-blind, placebo-controlled study. Arch Dermatol, 2012, 148(3):307-314.
10. Li EK, Zhu TY, Hung VY, et al. Ibandronate increases cortical bone density in patients with systemic lupus erythematosus on long-term glucocorticoid. Arthritis Res Ther, 2010, 12(5):1-8.
11. Takei T, Itabashi M, Tsukada M, et al. Risedronate therapy for the prevention of steroid-induced osteoporosis in patients with minimal-change nephrotic syndrome. Inter Med, 2010, 49(19):2065-2070.
12. Stoch SA, Saag KG, Greenwald M. 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.
13. Yeap SS, Fauzi AR, Kong NC, et al. A comparison of calcium, calcitriol, and alendronate in corticosteroid-treated premenopausal patients with systemic lupus erythematosus. J Rheumatol, 2008, 35(35):2344-2347.
14. Okada Y, Nawata M, Nakayamada S, et al. Alendronate protects premenopausal women from bone loss and fracture associated with high-dose glucocorticoid therapy. J Rheumatol, 2008, 35(11):2249-2254.
15. Lems WF, Lodder MC, Lips P, et al. Positive effect of alendronate on bone mineral density and markers of bone turnover in patients with rheumatoid arthritis on chronic treatment with low-dose prednisone:a randomized, double-blind, placebo-controlled trial. Osteoporos Int, 2006, 17(5):716-723.
16. Boutsen Y, Jamart J, Esselinckx W, et al. 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(1):104-112.
17. 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 Rheumatol, 2001, 44(1):202-211.
18. Lau EM, Woo J, Chan YH, et al. Alendronate for the prevention of bone loss in patients on inhaled steroid therapy. Bone, 2001, 29(6):506-510.
19. 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(6):1006-1013.
20. Jenkins EA, Walker-Bone KE, Wood A, et al. The prevention of corticosteroid-induced bone loss with intermittent cyclical etidronate. Scand J Rheumatol, 1999, 28(3):152-156.
21. Geusens P, Dequeker J, Vanhoof J, et al. Cyclical etidronate increases bone density in the spine and hip of postmenopausal women receiving long term corticosteroid treatment. A double blind, randomised placebo controlled study. Ann Rheum Dis, 1998, 57(12):724-727.
22. 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.
23. 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(5):292-299.
24. Adachi JD, Bensen WG, Brown J, et al. Intermittent etidronate therapy to prevent corticosteroid-induced osteoporosis. N Engl J Med, 1997, 337(6):382-387.
25. 楊雪驊, 陳志君, 左權, 等. 阿侖膦酸鈉、阿法骨化醇、碳酸鈣聯合應用治療糖皮質激素誘發的骨質疏松癥32例療效分析. 上海醫藥, 2014, (1):28-31.
26. 程勇軍, 王文龍, 李云生, 等. 阿侖膦酸鈉治療糖皮質激素依賴的腎病綜合征研究. 中華全科醫學, 2014, 12(3):365-367.
27. 張啟祥, 孔建平. 利塞膦酸鈉對糖皮質激素誘導的骨質疏松的療效觀察. 中國現代應用藥學, 2011, (6):585-588.
28. 全會標, 高勇義. 利塞膦酸鈉臨床研究進展. 醫學綜述, 2007, 13(1):66-68.
29. Lanza FL, Hunt RH, Thomson AB, et al. Endoscopic comparison of esophageal and gastroduodenal effects of risedronate and alendronate in postmenopausal women. Gastroenterology, 2000, 119(3):631-638.
30. Lekamwasam S, Adachi J D, Agnusdei D, et al. A framework for the development of guidelines for the management of glucocorticoid-induced osteoporosis. N Engl J Med, 2012, 23(9):2257-2276.
31. de Nijs RN, Jacobs JW, Lems WF, et al. Alendronate or alfacalcidol in glucocorticoid-induced osteoporosis. N Engl J Med, 2006, 355(7):675-684.
32. Thomas T, Horlait S, Ringe JD, et al. Oral bisphosphonates reduce the risk of clinical fractures in glucocorticoid-induced osteoporosis in clinical practice. Osteoporos Int, 2013, 24(1):263-269.
33. 楊琳, 田金徽, 何智余, 等. 阿侖膦酸鈉對糖皮質激素導致骨質疏松防治作用的Meta分析. 中華內科雜志, 2013, 52(10):838-843.

Chinese Journal of Evidence-Based Medicine

Efficacy and Safety of Bisphosphonates for Glucocorticoid Induced Osteoporosis: A Systematic Review

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