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.
Similar content being viewed by others
References
NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis, and Therapy (2001) Osteoporosis prevention, diagnosis, and therapy. JAMA 285(6):785–795
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):368–381
WHO Scientific Group (2003) Prevention and management of osteoporosis. WHO technical report series. World Health Organization, Geneva
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–S27
U.S. Food and Drug Administration Drug Details. http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.DrugDetails. Accessed March 1st 2014
AMGEN Prolia (denosumab) [Prescribing Information]. http://pi.amgen.com/united_states/prolia/prolia_pi.pdf. Accessed March 1st 2014
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
Moher D, Liberati A, Tetzlaff J, Altman DG (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 339:b2535. doi:10.1136/bmj.b2535
Higgins JPT, Green S (editors) (2011) Cochrane handbook for systematic reviews of interventions version 5.1.0 [updated March 2011]
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):451–455
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
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
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
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
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
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
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
Tsai JN, Uihlein AV, Lee H, Kumbhani R, Siwila-Sackman E, McKay EA, Burnett-Bowie SA, Neer RM, Leder BZ (2013) Teriparatide and denosumab, alone or combined, in women with postmenopausal osteoporosis: the DATA study randomised trial. Lancet 382(9886):50–56. doi:10.1016/s0140-6736(13)60856-9
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
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
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
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
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
Beck TJ, Lewiecki EM, Miller PD, Felsenberg D, Liu Y, Ding B, Libanati C (2008) Effects of denosumab on the geometry of the proximal femur in postmenopausal women in comparison with alendronate. J Clin Densitom 11(3):351–359. doi:10.1016/j.jocd.2008.04.001
Baron R, Ferrari S, Russell RG (2011) Denosumab and bisphosphonates: different mechanisms of action and effects. Bone 48(4):677–692. doi:10.1016/j.bone.2010.11.020
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
Lin T, Wang C, Cai XZ, Zhao X, Shi MM, Ying ZM, Yuan FZ, Guo C, Yan SG (2012) Comparison of clinical efficacy and safety between denosumab and alendronate in postmenopausal women with osteoporosis: a meta-analysis. Int J Clin Pract 66(4):399–408. doi:10.1111/j.1742-1241.2011.02806.x
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
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
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
Green W (2010) Denosumab (Prolia) Injection: a new approach to the treatment of women with postmenopausal osteoporosis. Pharm Ther 35(10):553–559
Kanis JA, Alexandre JM, Bone HG, Abadie E, Brasseur D, Chassany O, Durrleman S, Lekkerkerker JF, Caulin F (2003) Study design in osteoporosis: a European perspective. J Bone Miner Res 18(6):1133–1138. doi:10.1359/jbmr.2003.18.6.1133
Acknowledgments
We gratefully acknowledge the contributions of Dr. Alexis F. Turgeon and Amélie Boutin for their methodological assistance. We also acknowledge the contribution of the administrative assistant Julie Parrot.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Funding
C Beaudoin received a scholarship from the CHU de Québec.
Conflicts of interest
C Beaudoin, S Jean and L Moore have no conflict of interest to disclose.
L Bessette received remuneration from Amgen, Eli Lilly, Novartis, and Merck; consultant/advisory role to Amgen, UCB, Pfizer, Abbvie, and Hoffmann-La Roche; and funds from Abbott, Amgen, Bristol-Myers Squibb, Eli Lilly, Merck, Novartis, Pfizer, Roche, Sanofiaventis, Servier, Warner Chilcott, and Takeda.
L-G Ste-Marie received research grants from Amgen and Eli Lilly; educational grants from Amgen, Eli Lilly, Genzyme, and Novartis; and board membership from Amgen, Eli Lilly, and Merck.
J P Brown received research grants from Amgen and Eli Lilly; board membership for Amgen, Eli Lilly, and Merck; consulting and speaking fees from Amgen and Eli Lilly.
Electronic supplementary material
Below is the link to the electronic supplementary material.
ESM 1
(PDF 374 kb)
Rights and permissions
About this article
Cite this article
Beaudoin, C., Jean, S., Bessette, L. et al. Denosumab compared to other treatments to prevent or treat osteoporosis in individuals at risk of fracture: a systematic review and meta-analysis. Osteoporos Int 27, 2835–2844 (2016). https://doi.org/10.1007/s00198-016-3607-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00198-016-3607-6