Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Osteoporosis International
Published in: Osteoporosis International 10/2015

Open Access 01-10-2015 | Original Article

Persistence with denosumab and persistence with oral bisphosphonates for the treatment of postmenopausal osteoporosis: a retrospective, observational study, and a meta-analysis

Authors: L. Karlsson, J. Lundkvist, E. Psachoulia, M. Intorcia, O. Ström

Published in: Osteoporosis International | Issue 10/2015

Login to get access

Abstract

Summary

The objectives of this study were to estimate persistence with denosumab and put these results in context by conducting a review of persistence with oral bisphosphonates. Persistence with denosumab was found to be higher than with oral bisphosphonates.

Purpose

This study had two objectives: to analyse persistence in Swedish women initiating denosumab for treatment of postmenopausal osteoporosis (PMO) and to put these findings in context by conducting a literature review and meta-analysis of persistence data for oral bisphosphonates.

Methods

The study used the Swedish Prescribed Drug Register and included women aged at least 50 years initiating denosumab between May 2010 and July 2012. One injection of denosumab was defined as 6-month persistence. Women were considered persistent for another 6 months if they filled their next prescription within 6 months + 56 days and survival analysis applied to the data. A literature search was conducted in PubMed to identify retrospective studies of persistence with oral bisphosphonates and pooled persistence estimates were calculated using a random-effects model.

Results

The study identified 2,315 women who were incident denosumab users. Mean age was 74 years and 61 % had been previously treated for PMO. At 12 and 24 months, persistence with denosumab was 83 % (95 % CI, 81–84 %) and 62 % (95 % CI, 60–65 %), respectively. The literature search identified 40 articles for inclusion in the meta-analysis. At 12 and 24 months, persistence with oral bisphosphonates ranged from 10 % to 78 % and from 16 % to 46 %, with pooled estimates of 45 % and 30 %, respectively.

Conclusion

These data from the Swedish Prescribed Drug Register and literature review suggest that persistence was higher with denosumab than with oral bisphosphonates.
Literature
1.
Kanis JA, McCloskey EV, Johansson H, Cooper C, Rizzoli R, Reginster JY, Scientific Advisory Board of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO), The Committee of Scientific Advisors of the International Osteoporosis Foundation (IOF) (2013) European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Osteoporos Int 24:23–57PubMedCentralCrossRefPubMed
2.
3.
4.
Cramer JA, Roy A, Burrell A, Fairchild CJ, Fuldeore MJ, Ollendorf DA, Wong PK (2008) Medication compliance and persistence: terminology and definitions. Value Health 11:44–47CrossRefPubMed
5.
Siris ES, Harris ST, Rosen CJ, Barr CE, Arvesen JN, Abbott TA, Silverman S (2006) Adherence to bisphosphonate therapy and fracture rates in osteoporotic women: relationship to vertebral and nonvertebral fractures from 2 US claims databases. Mayo Clin Proc 81:1013–1022CrossRefPubMed
6.
Landfeldt E, Ström O, Robbins S, Borgstrom F (2012) Adherence to treatment of primary osteoporosis and its association to fractures—the Swedish Adherence Register Analysis (SARA). Osteoporos Int 23:433–443CrossRefPubMed
7.
Lakatos P, Toth E, Cina Z, Lang Z, Psachoulia E, Intorcia M (2013) Persistence and compliance to treatment for osteoporosis in postmenopausal women in Hungary: A retrospective cohort study. Poster presented at the ISPOR 16th Annual European Congress, 2013, Dublin, Ireland, Poster ID: 34654
8.
Compston JE, Seeman E (2006) Compliance with osteoporosis therapy is the weakest link. Lancet 368:973–974CrossRefPubMed
9.
Ström O, Borgstrom F, Kanis JA, Compston J, Cooper C, McCloskey EV, Jonsson B (2011) Osteoporosis: burden, health care provision and opportunities in the EU: a report prepared in collaboration with the International Osteoporosis Foundation (IOF) and the European Federation of Pharmaceutical Industry Associations (EFPIA). Arch Osteoporos 6:59–155CrossRefPubMed
10.
Jonsson B, Ström O, Eisman JA, Papaioannou A, Siris ES, Tosteson A, Kanis JA (2011) Cost-effectiveness of denosumab for the treatment of postmenopausal osteoporosis. Osteoporos Int 22:967–982CrossRefPubMed
11.
Hiligsmann M, Boonen A, Rabenda V, Reginster JY (2012) The importance of integrating medication adherence into pharmacoeconomic analyses: the example of osteoporosis. Expert Rev Pharmacoecon Outcomes Res 12:159–166CrossRefPubMed
12.
Hernlund E, Svedbom A, Ivergard M, Compston J, Cooper C, Stenmark J, McCloskey EV, Jonsson B, Kanis JA (2013) Osteoporosis in the European Union: medical management, epidemiology and economic burden. A report prepared in collaboration with the International Osteoporosis Foundation (IOF) and the European Federation of Pharmaceutical Industry Associations (EFPIA). Arch Osteoporos 8:136PubMedCentralCrossRefPubMed
13.
14.
Gnant M, Pfeiler G, Dubsky PC, Hubalek M, Greil R, Jakesz R, Wette V, Balic M, Haslbauer F, Melbinger E et al (2015) Adjuvant denosumab in breast cancer (ABCSG-18): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet. doi:10.​1016/​S0140-6736(15)60995-3
15.
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 23:317–372PubMedCentralCrossRefPubMed
16.
Silverman SL, Siris E, Kendler DL, Belazi D, Brown JP, Gold DT, Lewiecki EM, Papaioannou A, Simonelli C, Ferreira I et al (2015) Persistence at 12 months with denosumab in postmenopausal women with osteoporosis: interim results from a prospective observational study. Osteoporos Int 26:361–372PubMedCentralCrossRefPubMed
17.
Hadji P, Papaioannou N, Gielen E, Tepie M, Zhang E, Frieling P, Geusens P, Makras P, Resch H, Möller G et al (2015) Persistence, adherence, and medication-taking behavior in women with postmenopausal osteoporosis receiving denosumab in routine practice in Germany, Austria, Greece, and Belgium: 12-month results from a European non-interventional study. Osteoporos Int. doi:10.​1007/​s00198-015-3164-4
18.
19.
20.
21.
22.
Adachi JD, Adami S, Gehlbach S, Anderson FA Jr, Boonen S, Chapurlat RD, Compston JE, Cooper C, Delmas P, Diez-Perez A et al (2010) Impact of prevalent fractures on quality of life: baseline results from the global longitudinal study of osteoporosis in women. Mayo Clin Proc 85:806–813PubMedCentralCrossRefPubMed
23.
Silverman SL, Gold DT, Cramer JA (2007) Reduced fracture rates observed only in patients with proper persistence and compliance with bisphosphonate therapies. South Med J 100:1214–1218CrossRefPubMed
24.
Imaz I, Zegarra P, Gonzalez-Enriquez J, Rubio B, Alcazar R, Amate JM (2010) Poor bisphosphonate adherence for treatment of osteoporosis increases fracture risk: systematic review and meta-analysis. Osteoporos Int 21:1943–1951CrossRefPubMed
25.
Cramer JA, Gold DT, Silverman SL, Lewiecki EM (2007) A systematic review of persistence and compliance with bisphosphonates for osteoporosis. Osteoporos Int 18:1023–1031CrossRefPubMed
26.
Kothawala P, Badamgarav E, Ryu S, Miller RM, Halbert RJ (2007) Systematic review and meta-analysis of real-world adherence to drug therapy for osteoporosis. Mayo Clin Proc 82:1493–1501CrossRefPubMed
27.
28.
Cramer JA, Silverman S, Gold DT (2007) Methodological considerations in using claims databases to evaluate persistence with bisphosphonates for osteoporosis. Curr Med Res Opin 23:2369–2377CrossRefPubMed
29.
30.
Brankin E, Walker M, Lynch N, Aspray T, Lis Y, Cowell W (2006) The impact of dosing frequency on compliance and persistence with bisphosphonates among postmenopausal women in the UK: evidence from three databases. Curr Med Res Opin 22:1249–1256CrossRefPubMed
31.
Burden AM, Paterson JM, Solomon DH, Mamdani M, Juurlink DN, Cadarette SM (2012) Bisphosphonate prescribing, persistence and cumulative exposure in Ontario, Canada. Osteoporos Int 23:1075–1082PubMedCentralCrossRefPubMed
32.
Cheen MH, Kong MC, Zhang RF, Tee FM, Chandran M (2012) Adherence to osteoporosis medications amongst Singaporean patients. Osteoporos Int 23:1053–1060CrossRefPubMed
33.
Cotte FE, Fardellone P, Mercier F, Gaudin AF, Roux C (2010) Adherence to monthly and weekly oral bisphosphonates in women with osteoporosis. Osteoporos Int 21:145–155PubMedCentralCrossRefPubMed
34.
Cotte FE, Mercier F, De Pouvourville G (2008) Relationship between compliance and persistence with osteoporosis medications and fracture risk in primary health care in France: a retrospective case–control analysis. Clin Ther 30:2410–2422CrossRefPubMed
35.
Cramer JA, Amonkar MM, Hebborn A, Altman R (2005) Compliance and persistence with bisphosphonate dosing regimens among women with postmenopausal osteoporosis. Curr Med Res Opin 21:1453–1460CrossRefPubMed
36.
Cramer JA, Lynch NO, Gaudin AF, Walker M, Cowell W (2006) The effect of dosing frequency on compliance and persistence with bisphosphonate therapy in postmenopausal women: a comparison of studies in the United States, the United Kingdom, and France. Clin Ther 28:1686–1694CrossRefPubMed
37.
Gold DT, Martin BC, Frytak JR, Amonkar MM, Cosman F (2007) A claims database analysis of persistence with alendronate therapy and fracture risk in post-menopausal women with osteoporosis. Curr Med Res Opin 23:585–594CrossRefPubMed
38.
Huybrechts KF, Ishak KJ, Caro JJ (2006) Assessment of compliance with osteoporosis treatment and its consequences in a managed care population. Bone 38:922–928CrossRefPubMed
39.
Jones TJ, Petrella RJ, Crilly R (2008) Determinants of persistence with weekly bisphosphonates in patients with osteoporosis. J Rheumatol 35:1865–1873PubMed
40.
Li L, Roddam A, Gitlin M, Taylor A, Shepherd S, Shearer A, Jick S (2012) Persistence with osteoporosis medications among postmenopausal women in the UK General Practice Research Database. Menopause 19:33–40CrossRefPubMed
41.
Lo JC, Pressman AR, Omar MA, Ettinger B (2006) Persistence with weekly alendronate therapy among postmenopausal women. Osteoporos Int 17:922–928CrossRefPubMed
42.
McCombs JS, Thiebaud P, McLaughlin-Miley C, Shi J (2004) Compliance with drug therapies for the treatment and prevention of osteoporosis. Maturitas 48:271–287CrossRefPubMed
43.
Netelenbos JC, Geusens PP, Ypma G, Buijs SJ (2011) Adherence and profile of non-persistence in patients treated for osteoporosis—a large-scale, long-term retrospective study in The Netherlands. Osteoporos Int 22:1537–1546PubMedCentralCrossRefPubMed
44.
Penning-van Beest FJ, Goettsch WG, Erkens JA, Herings RM (2006) Determinants of persistence with bisphosphonates: a study in women with postmenopausal osteoporosis. Clin Ther 28:236–242CrossRefPubMed
45.
Rabenda V, Mertens R, Fabri V, Vanoverloop J, Sumkay F, Vannecke C, Deswaef A, Verpooten GA, Reginster JY (2008) Adherence to bisphosphonates therapy and hip fracture risk in osteoporotic women. Osteoporos Int 19:811–818CrossRefPubMed
46.
Solomon DH, Avorn J, Katz JN, Finkelstein JS, Arnold M, Polinski JM, Brookhart MA (2005) Compliance with osteoporosis medications. Arch Intern Med 165:2414–2419CrossRefPubMed
47.
Ström O, Landfeldt E (2012) The association between automatic generic substitution and treatment persistence with oral bisphosphonates. Osteoporos Int 23:2201–2209CrossRefPubMed
48.
van den Boogaard CH, Breekveldt-Postma NS, Borggreve SE, Goettsch WG, Herings RM (2006) Persistent bisphosphonate use and the risk of osteoporotic fractures in clinical practice: a database analysis study. Curr Med Res Opin 22:1757–1764CrossRefPubMed
49.
Vanelli M, Pedan A, Liu N, Hoar J, Messier D, Kiarsis K (2009) The role of patient inexperience in medication discontinuation: a retrospective analysis of medication nonpersistence in seven chronic illnesses. Clin Ther 31:2628–2652CrossRefPubMed
50.
Weycker D, Macarios D, Edelsberg J, Oster G (2006) Compliance with drug therapy for postmenopausal osteoporosis. Osteoporos Int 17:1645–1652CrossRefPubMed
51.
Yeaw J, Benner JS, Walt JG, Sian S, Smith DB (2009) Comparing adherence and persistence across 6 chronic medication classes. J Manag Care Pharm 15:728–740PubMed
52.
Yu SF, Chou CL, Lai HM, Chen YC, Chiu CK, Kuo MC, Su YJ, Chen CJ, Cheng TT (2012) Adherence to anti-osteoporotic regimens in a Southern Taiwanese population treated according to guidelines: a hospital-based study. Int J Rheum Dis 15:297–305CrossRefPubMed
53.
Gallagher AM, Rietbrock S, Olson M, van Staa TP (2008) Fracture outcomes related to persistence and compliance with oral bisphosphonates. J Bone Miner Res 23:1569–1575CrossRefPubMed
54.
Gold DT, Trinh H, Safi W (2009) Weekly versus monthly drug regimens: 1-year compliance and persistence with bisphosphonate therapy. Curr Med Res Opin 25:1831–1839CrossRefPubMed
55.
Hadji P, Claus V, Ziller V, Intorcia M, Kostev K, Steinle T (2012) GRAND: the German retrospective cohort analysis on compliance and persistence and the associated risk of fractures in osteoporotic women treated with oral bisphosphonates. Osteoporos Int 23:223–231CrossRefPubMed
56.
Weiss TW, Henderson SC, McHorney CA, Cramer JA (2007) Persistence across weekly and monthly bisphosphonates: analysis of US retail pharmacy prescription refills. Curr Med Res Opin 23:2193–2203CrossRefPubMed
57.
Hansen C, Pedersen BD, Konradsen H, Abrahamsen B (2013) Anti-osteoporotic therapy in Denmark—predictors and demographics of poor refill compliance and poor persistence. Osteoporos Int 24:2079–2097CrossRefPubMed
58.
Cheng TT, Yu SF, Hsu CY, Chen SH, Su BY, Yang TS (2013) Differences in adherence to osteoporosis regimens: a 2-year analysis of a population treated under specific guidelines. Clin Ther 35:1005–1015CrossRefPubMed
59.
Curtis JR, Westfall AO, Allison JJ, Freeman A, Saag KG (2006) Channeling and adherence with alendronate and risedronate among chronic glucocorticoid users. Osteoporos Int 17:1268–1274CrossRefPubMed
60.
McGowan B, Bennett K, Casey MC, Doherty J, Silke C, Whelan B (2013) Comparison of prescribing and adherence patterns of anti-osteoporotic medications post-admission for fragility type fracture in an urban teaching hospital and a rural teaching hospital in Ireland between 2005 and 2008. Ir J Med Sci 182:601–608CrossRefPubMed
61.
van Boven JF, de Boer PT, Postma MJ, Vegter S (2013) Persistence with osteoporosis medication among newly-treated osteoporotic patients. J Bone Miner Metab 31:562–570CrossRefPubMed
62.
Ziller V, Kostev K, Kyvernitakis I, Boeckhoff J, Hadji P (2012) Persistence and compliance of medications used in the treatment of osteoporosis—analysis using a large scale, representative, longitudinal German database. Int J Clin Pharmacol Ther 50:315–322CrossRefPubMed
63.
Wade SW, Curtis JR, Yu J, White J, Stolshek BS, Merinar C, Balasubramanian A, Kallich JD, Adams JL, Viswanathan HN (2012) Medication adherence and fracture risk among patients on bisphosphonate therapy in a large United States health plan. Bone 50:870–875CrossRefPubMed
64.
Balasubramanian A, Brookhart MA, Goli V, Critchlow CW (2013) Discontinuation and reinitiation patterns of osteoporosis treatment among commercially insured postmenopausal women. Int J Gen Med 6:839–848PubMedCentralCrossRefPubMed
65.
Chiu CK, Kuo MC, Yu SF, Su BY, Cheng TT (2013) Adherence to osteoporosis regimens among men and analysis of risk factors of poor compliance: a 2-year analytical review. BMC Musculoskelet Disord 14:276PubMedCentralCrossRefPubMed
66.
Xu Y, Viswanathan HN, Ward MA, Clay B, Adams JL, Stolshek BS, Kallich JD, Fine S, Saag KG (2013) Patterns of osteoporosis treatment change and treatment discontinuation among commercial and medicare advantage prescription drug members in a national health plan. J Eval Clin Pract 19:50–59CrossRefPubMed
67.
Sheehy O, Kindundu C, Barbeau M, LeLorier J (2009) Adherence to weekly oral bisphosphonate therapy: cost of wasted drugs and fractures. Osteoporos Int 20:1583–1594CrossRefPubMed
68.
Silverman SL, Gold DT (2008) Compliance and persistence with osteoporosis therapies. Curr Rheumatol Rep 10:118–122CrossRefPubMed
69.
de Groen PC, Lubbe DF, Hirsch LJ, Daifotis A, Stephenson W, Freedholm D, Pryor-Tillotson S, Seleznick MJ, Pinkas H, Wang KK (1996) Esophagitis associated with the use of alendronate. N Engl J Med 335:1016–1021CrossRefPubMed
Metadata
Title
Persistence with denosumab and persistence with oral bisphosphonates for the treatment of postmenopausal osteoporosis: a retrospective, observational study, and a meta-analysis
Authors
L. Karlsson
J. Lundkvist
E. Psachoulia
M. Intorcia
O. Ström
Publication date
01-10-2015
Publisher
Springer London
Published in
Osteoporosis International / Issue 10/2015
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-015-3253-4

Other articles of this Issue 10/2015

Osteoporosis International 10/2015 Go to the issue

Review

Orthogeriatrics in the management of frail older patients with a fragility fracture

Original Article

Effect of vitamin D supplementation alone on muscle function in postmenopausal women: a randomized, double-blind, placebo-controlled clinical trial

Original Article

Bone strength and muscle properties in postmenopausal women with and without a recent distal radius fracture

Original Article

Denosumab versus zoledronic acid in patients previously treated with zoledronic acid

Original Article

Bone structure assessed by HR-pQCT, TBS and DXL in adult patients with different types of osteogenesis imperfecta

Original Article

Exercise and fractures in postmenopausal women. Final results of the controlled Erlangen Fitness and Osteoporosis Prevention Study (EFOPS)