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Published in: Osteoporosis International 9/2016

01-09-2016 | Original Article

Denosumab compared to other treatments to prevent or treat osteoporosis in individuals at risk of fracture: a systematic review and meta-analysis

Authors: C. Beaudoin, S. Jean, L. Bessette, L.-G. Ste-Marie, L. Moore, J. P. Brown

Published in: Osteoporosis International | Issue 9/2016

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Abstract

Summary

The aim of this review is to compare the efficacy and safety of denosumab over other treatments for osteoporosis. The results of this study suggest that the safety of denosumab and its efficacy in reducing fractures is not significantly different from bisphosphonates. Denosumab was, however, more effective in increasing bone mineral density.

Introduction

This study was conducted to compare the efficacy and safety of denosumab over other pharmacological treatments for osteoporosis in individuals at risk of fracture.

Methods

Randomised controlled trials comparing denosumab with another pharmacological treatment for osteoporosis were searched in MEDLINE, EMBASE and CENTRAL. Identified articles were screened by two independent reviewers and assessed for inclusion. Data from included studies were extracted and meta-analyses were conducted using random effects models.

Results

Nine studies including a total of 4890 postmenopausal women were identified. The follow-up period varied from 12 to 24 months. In all studies except one, the comparator treatment was a bisphosphonate. There was no statistically significant difference between patients receiving denosumab and those receiving a bisphosphonate in terms of fracture risk (RR[95 % CI] = 1.15 [0.84–1.58]), adverse events (RR[95 % CI] = 0.99 [0.96–1.02]) or deaths (OR[95 % CI] = 0.58 [0.12–2.71]). Withdrawals due to adverse events were less frequent in denosumab than in other treatment groups but the difference did not reach statistical significance (OR[95 % CI] = 0.68 [0.45–1.04]). The percent change in bone mineral density at the total hip, lumbar spine, femoral neck and one-third radius was significantly higher in participants who received denosumab (e.g. mean difference [95 % CI] at the total hip: 1.06 [0.86–1.25]).

Conclusions

These results suggest that, after 12 to 24 months, the safety and efficacy of denosumab for reducing fracture risk is not significantly different from bisphosphonates despite higher gains in bone mineral density. In a clinical setting, denosumab may demonstrate greater effectiveness.
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Literature
1.
go back to reference NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis, and Therapy (2001) Osteoporosis prevention, diagnosis, and therapy. JAMA 285(6):785–795CrossRef NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis, and Therapy (2001) Osteoporosis prevention, diagnosis, and therapy. JAMA 285(6):785–795CrossRef
2.
go back to reference Kanis JA (1994) Assessment of fracture risk and its application to screening for postmenopausal osteoporosis: synopsis of a WHO report. WHO Study Group. Osteoporos Int 4(6):368–381CrossRefPubMed Kanis JA (1994) Assessment of fracture risk and its application to screening for postmenopausal osteoporosis: synopsis of a WHO report. WHO Study Group. Osteoporos Int 4(6):368–381CrossRefPubMed
3.
go back to reference WHO Scientific Group (2003) Prevention and management of osteoporosis. WHO technical report series. World Health Organization, Geneva WHO Scientific Group (2003) Prevention and management of osteoporosis. WHO technical report series. World Health Organization, Geneva
4.
go back to reference Binkley NC, Schmeer P, Wasnich RD, Lenchik L (2002) What are the criteria by which a densitometric diagnosis of osteoporosis can be made in males and non-Caucasians? J Clin Densitom 5(Suppl):S19–S27CrossRefPubMed Binkley NC, Schmeer P, Wasnich RD, Lenchik L (2002) What are the criteria by which a densitometric diagnosis of osteoporosis can be made in males and non-Caucasians? J Clin Densitom 5(Suppl):S19–S27CrossRefPubMed
7.
go back to reference Cummings SR, San Martin J, 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 (2009) Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med 361(8):756–765. doi:10.1056/NEJMoa0809493 CrossRefPubMed Cummings SR, San Martin J, 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 (2009) Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med 361(8):756–765. doi:10.​1056/​NEJMoa0809493 CrossRefPubMed
9.
go back to reference Higgins JPT, Green S (editors) (2011) Cochrane handbook for systematic reviews of interventions version 5.1.0 [updated March 2011] Higgins JPT, Green S (editors) (2011) Cochrane handbook for systematic reviews of interventions version 5.1.0 [updated March 2011]
10.
go back to reference Wong SS, Wilczynski NL, Haynes RB (2006) Comparison of top-performing search strategies for detecting clinically sound treatment studies and systematic reviews in MEDLINE and EMBASE. J Med Libr Assoc 94(4):451–455PubMedPubMedCentral Wong SS, Wilczynski NL, Haynes RB (2006) Comparison of top-performing search strategies for detecting clinically sound treatment studies and systematic reviews in MEDLINE and EMBASE. J Med Libr Assoc 94(4):451–455PubMedPubMedCentral
11.
go back to reference Bradburn MJ, Deeks JJ, Berlin JA, Russell Localio A (2007) Much ado about nothing: a comparison of the performance of meta-analytical methods with rare events. Stat Med 26(1):53–77. doi:10.1002/sim.2528 CrossRefPubMed Bradburn MJ, Deeks JJ, Berlin JA, Russell Localio A (2007) Much ado about nothing: a comparison of the performance of meta-analytical methods with rare events. Stat Med 26(1):53–77. doi:10.​1002/​sim.​2528 CrossRefPubMed
12.
go back to reference Brown JP, Prince RL, Deal C, Recker RR, Kiel DP, de Gregorio LH, Hadji P, Hofbauer LC, Alvaro-Gracia JM, Wang H, Austin M, Wagman RB, Newmark R, Libanati C, San Martin J, Bone HG (2009) Comparison of the effect of denosumab and alendronate on BMD and biochemical markers of bone turnover in postmenopausal women with low bone mass: a randomized, blinded, phase 3 trial. J Bone Miner Res 24(1):153–161. doi:10.1359/jbmr.080901 CrossRefPubMed Brown JP, Prince RL, Deal C, Recker RR, Kiel DP, de Gregorio LH, Hadji P, Hofbauer LC, Alvaro-Gracia JM, Wang H, Austin M, Wagman RB, Newmark R, Libanati C, San Martin J, Bone HG (2009) Comparison of the effect of denosumab and alendronate on BMD and biochemical markers of bone turnover in postmenopausal women with low bone mass: a randomized, blinded, phase 3 trial. J Bone Miner Res 24(1):153–161. doi:10.​1359/​jbmr.​080901 CrossRefPubMed
13.
go back to reference Kendler DL, Roux C, Benhamou CL, Brown JP, Lillestol M, Siddhanti S, Man HS, San Martin J, Bone HG (2010) Effects of denosumab on bone mineral density and bone turnover in postmenopausal women transitioning from alendronate therapy. J Bone Miner Res 25(1):72–81. doi:10.1359/jbmr.090716 CrossRefPubMed Kendler DL, Roux C, Benhamou CL, Brown JP, Lillestol M, Siddhanti S, Man HS, San Martin J, Bone HG (2010) Effects of denosumab on bone mineral density and bone turnover in postmenopausal women transitioning from alendronate therapy. J Bone Miner Res 25(1):72–81. doi:10.​1359/​jbmr.​090716 CrossRefPubMed
14.
go back to reference Seeman E, Delmas PD, Hanley DA, Sellmeyer D, Cheung AM, Shane E, Kearns A, Thomas T, Boyd SK, Boutroy S, Bogado C, Majumdar S, Fan M, Libanati C, Zanchetta J (2010) Microarchitectural deterioration of cortical and trabecular bone: differing effects of denosumab and alendronate. J Bone Miner Res 25(8):1886–1894. doi:10.1002/jbmr.81 CrossRefPubMedPubMedCentral Seeman E, Delmas PD, Hanley DA, Sellmeyer D, Cheung AM, Shane E, Kearns A, Thomas T, Boyd SK, Boutroy S, Bogado C, Majumdar S, Fan M, Libanati C, Zanchetta J (2010) Microarchitectural deterioration of cortical and trabecular bone: differing effects of denosumab and alendronate. J Bone Miner Res 25(8):1886–1894. doi:10.​1002/​jbmr.​81 CrossRefPubMedPubMedCentral
15.
go back to reference Kendler DL, McClung MR, Freemantle N, Lillestol M, Moffett AH, Borenstein J, Satram-Hoang S, Yang YC, Kaur P, Macarios D, Siddhanti S (2011) Adherence, preference, and satisfaction of postmenopausal women taking denosumab or alendronate. Osteoporos Int 22(6):1725–1735. doi:10.1007/s00198-010-1378-z CrossRefPubMed Kendler DL, McClung MR, Freemantle N, Lillestol M, Moffett AH, Borenstein J, Satram-Hoang S, Yang YC, Kaur P, Macarios D, Siddhanti S (2011) Adherence, preference, and satisfaction of postmenopausal women taking denosumab or alendronate. Osteoporos Int 22(6):1725–1735. doi:10.​1007/​s00198-010-1378-z CrossRefPubMed
16.
go back to reference Freemantle N, Satram-Hoang S, Tang ET, Kaur P, Macarios D, Siddhanti S, Borenstein J, Kendler DL (2012) Final results of the DAPS (Denosumab Adherence Preference Satisfaction) study: a 24-month, randomized, crossover comparison with alendronate in postmenopausal women. Osteoporos Int 23(1):317–326. doi:10.1007/s00198-011-1780-1 CrossRefPubMed Freemantle N, Satram-Hoang S, Tang ET, Kaur P, Macarios D, Siddhanti S, Borenstein J, Kendler DL (2012) Final results of the DAPS (Denosumab Adherence Preference Satisfaction) study: a 24-month, randomized, crossover comparison with alendronate in postmenopausal women. Osteoporos Int 23(1):317–326. doi:10.​1007/​s00198-011-1780-1 CrossRefPubMed
17.
go back to reference Recknor C, Czerwinski E, Bone HG, Bonnick SL, Binkley N, Palacios S, Moffett A, Siddhanti S, Ferreira I, Ghelani P, Wagman RB, Hall JW, Bolognese MA, Benhamou CL (2013) Denosumab compared with ibandronate in postmenopausal women previously treated with bisphosphonate therapy: a randomized open-label trial. Obstet Gynecol 121(6):1291–1299. doi:10.1097/AOG.0b013e318291718c CrossRefPubMed Recknor C, Czerwinski E, Bone HG, Bonnick SL, Binkley N, Palacios S, Moffett A, Siddhanti S, Ferreira I, Ghelani P, Wagman RB, Hall JW, Bolognese MA, Benhamou CL (2013) Denosumab compared with ibandronate in postmenopausal women previously treated with bisphosphonate therapy: a randomized open-label trial. Obstet Gynecol 121(6):1291–1299. doi:10.​1097/​AOG.​0b013e318291718c​ CrossRefPubMed
19.
go back to reference Leder BZ, Tsai JN, Uihlein AV, Burnett-Bowie SA, Zhu Y, Foley K, Lee H, Neer RM (2014) Two years of denosumab and teriparatide administration in postmenopausal women with osteoporosis (the DATA extension study): a randomized controlled trial. J Clin Endocrinol Metab:jc20134440. doi:10.1210/jc.2013-4440 Leder BZ, Tsai JN, Uihlein AV, Burnett-Bowie SA, Zhu Y, Foley K, Lee H, Neer RM (2014) Two years of denosumab and teriparatide administration in postmenopausal women with osteoporosis (the DATA extension study): a randomized controlled trial. J Clin Endocrinol Metab:jc20134440. doi:10.​1210/​jc.​2013-4440
20.
go back to reference Roux C, Hofbauer LC, Ho PR, Wark JD, Zillikens MC, Fahrleitner-Pammer A, Hawkins F, Micaelo M, Minisola S, Papaioannou N, Stone M, Ferreira I, Siddhanti S, Wagman RB, Brown JP (2014) Denosumab compared with risedronate in postmenopausal women suboptimally adherent to alendronate therapy: efficacy and safety results from a randomized open-label study. Bone 58:48–54. doi:10.1016/j.bone.2013.10.006 CrossRefPubMed Roux C, Hofbauer LC, Ho PR, Wark JD, Zillikens MC, Fahrleitner-Pammer A, Hawkins F, Micaelo M, Minisola S, Papaioannou N, Stone M, Ferreira I, Siddhanti S, Wagman RB, Brown JP (2014) Denosumab compared with risedronate in postmenopausal women suboptimally adherent to alendronate therapy: efficacy and safety results from a randomized open-label study. Bone 58:48–54. doi:10.​1016/​j.​bone.​2013.​10.​006 CrossRefPubMed
21.
go back to reference Miller PD, Pannacciulli N, Brown JP, Czerwinski E, Nedergaard BS, Bolognese MA, Malouf J, Bone HG, Reginster JY, Singer A, Wang C, Wagman RB, Cummings SR (2015) Denosumab compared with zoledronic acid in postmenopausal women with osteoporosis previously treated with oral bisphosphonates: efficacy and safety results from a randomized fouble-blind study. J Bone Miner Res 30(S1):S1. doi:10.1002/jbmr.2763 CrossRef Miller PD, Pannacciulli N, Brown JP, Czerwinski E, Nedergaard BS, Bolognese MA, Malouf J, Bone HG, Reginster JY, Singer A, Wang C, Wagman RB, Cummings SR (2015) Denosumab compared with zoledronic acid in postmenopausal women with osteoporosis previously treated with oral bisphosphonates: efficacy and safety results from a randomized fouble-blind study. J Bone Miner Res 30(S1):S1. doi:10.​1002/​jbmr.​2763 CrossRef
22.
go back to reference McClung MR, Lewiecki EM, Cohen SB, Bolognese MA, Woodson GC, Moffett AH, Peacock M, Miller PD, Lederman SN, Chesnut CH, Lain D, Kivitz AJ, Holloway DL, Zhang C, Peterson MC, Bekker PJ (2006) Denosumab in postmenopausal women with low bone mineral density. N Engl J Med 354(8):821–831. doi:10.1056/NEJMoa044459 CrossRefPubMed McClung MR, Lewiecki EM, Cohen SB, Bolognese MA, Woodson GC, Moffett AH, Peacock M, Miller PD, Lederman SN, Chesnut CH, Lain D, Kivitz AJ, Holloway DL, Zhang C, Peterson MC, Bekker PJ (2006) Denosumab in postmenopausal women with low bone mineral density. N Engl J Med 354(8):821–831. doi:10.​1056/​NEJMoa044459 CrossRefPubMed
23.
go back to reference Lewiecki EM, Miller PD, McClung MR, Cohen SB, Bolognese MA, Liu Y, Wang A, Siddhanti S, Fitzpatrick LA (2007) Two-year treatment with denosumab (AMG 162) in a randomized phase 2 study of postmenopausal women with low BMD. J Bone Miner Res 22(12):1832–1841. doi:10.1359/jbmr.070809 CrossRefPubMed Lewiecki EM, Miller PD, McClung MR, Cohen SB, Bolognese MA, Liu Y, Wang A, Siddhanti S, Fitzpatrick LA (2007) Two-year treatment with denosumab (AMG 162) in a randomized phase 2 study of postmenopausal women with low BMD. J Bone Miner Res 22(12):1832–1841. doi:10.​1359/​jbmr.​070809 CrossRefPubMed
24.
26.
go back to reference Murad MH, Drake MT, Mullan RJ, Mauck KF, Stuart LM, Lane MA, Abu Elnour NO, Erwin PJ, Hazem A, Puhan MA, Li T, Montori VM (2012) Clinical review. Comparative effectiveness of drug treatments to prevent fragility fractures: a systematic review and network meta-analysis. J Clin Endocrinol Metab 97(6):1871–1880. doi:10.1210/jc.2011-3060 CrossRefPubMed Murad MH, Drake MT, Mullan RJ, Mauck KF, Stuart LM, Lane MA, Abu Elnour NO, Erwin PJ, Hazem A, Puhan MA, Li T, Montori VM (2012) Clinical review. Comparative effectiveness of drug treatments to prevent fragility fractures: a systematic review and network meta-analysis. J Clin Endocrinol Metab 97(6):1871–1880. doi:10.​1210/​jc.​2011-3060 CrossRefPubMed
27.
28.
go back to reference Karlsson L, Lundkvist J, Psachoulia E, Intorcia M, Strom O (2015) Persistence with denosumab and persistence with oral bisphosphonates for the treatment of postmenopausal osteoporosis: a retrospective, observational study, and a meta-analysis. Osteoporos Int 26(10):2401–2411. doi:10.1007/s00198-015-3253-4 CrossRefPubMedPubMedCentral Karlsson L, Lundkvist J, Psachoulia E, Intorcia M, Strom O (2015) Persistence with denosumab and persistence with oral bisphosphonates for the treatment of postmenopausal osteoporosis: a retrospective, observational study, and a meta-analysis. Osteoporos Int 26(10):2401–2411. doi:10.​1007/​s00198-015-3253-4 CrossRefPubMedPubMedCentral
29.
go back to reference Institut national d’excellence en santé et en services sociaux (INESSS) (2014) Portrait de l’usage des bisphosphonates et du dénosumab chez les personnes de 50 ans ou plus souffrant d’ostéoporose couvertes par le régime public d’assurance médicaments. INESSS, Québec Institut national d’excellence en santé et en services sociaux (INESSS) (2014) Portrait de l’usage des bisphosphonates et du dénosumab chez les personnes de 50 ans ou plus souffrant d’ostéoporose couvertes par le régime public d’assurance médicaments. INESSS, Québec
30.
go back to reference Hiligsmann M, Boonen A, Dirksen CD, Ben Sedrine W, Reginster JY (2013) Cost-effectiveness of denosumab in the treatment of postmenopausal osteoporotic women. Expert Rev Pharmacoecon Outcomes Res 13(1):19–28. doi:10.1586/erp.12.76 CrossRefPubMed Hiligsmann M, Boonen A, Dirksen CD, Ben Sedrine W, Reginster JY (2013) Cost-effectiveness of denosumab in the treatment of postmenopausal osteoporotic women. Expert Rev Pharmacoecon Outcomes Res 13(1):19–28. doi:10.​1586/​erp.​12.​76 CrossRefPubMed
31.
go back to reference Green W (2010) Denosumab (Prolia) Injection: a new approach to the treatment of women with postmenopausal osteoporosis. Pharm Ther 35(10):553–559 Green W (2010) Denosumab (Prolia) Injection: a new approach to the treatment of women with postmenopausal osteoporosis. Pharm Ther 35(10):553–559
Metadata
Title
Denosumab compared to other treatments to prevent or treat osteoporosis in individuals at risk of fracture: a systematic review and meta-analysis
Authors
C. Beaudoin
S. Jean
L. Bessette
L.-G. Ste-Marie
L. Moore
J. P. Brown
Publication date
01-09-2016
Publisher
Springer London
Published in
Osteoporosis International / Issue 9/2016
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-016-3607-6

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