Top

Published in:

01-11-2020 | Osteoporosis | Review

Persistence and adherence to parenteral osteoporosis therapies: a systematic review

Authors: G. Koller, V. Goetz, B. Vandermeer, J. Homik, F. A. McAlister, D. Kendler, C. Ye

Published in: Osteoporosis International | Issue 11/2020

Abstract

Osteoporosis is a chronic disease of low bone mass and fragility. Treatment is frequently compromised by suboptimal medication compliance causing increased morbidity. This review investigates adherence and persistence to parenteral osteoporosis therapies. Findings reveal parenteral medications requiring reduced dosing frequency have higher compliance than oral therapies. This systematic review examines real-world adherence to parenteral osteoporosis therapies. We searched PubMed, Medline, and EMBASE databases for English language observational studies that examined patient adherence and/or persistence to parenteral osteoporosis treatments (teriparatide sc, ibandronate iv, zoledronic acid iv, and denosumab sc) in adults with osteoporosis published up to September 2018. Studies with only self-reported adherence or persistence data and those with less than 20 patients were excluded. Quality assessment of included studies was completed using the Newcastle-Ottawa quality assessment scale (NOS). We identified 40 eligible studies. Teriparatide was examined in 29 studies, with persistence rates of 10–87% (median 55%) at 1 year and 10–69% (median 29.5%) at 2 years, and adherence rates of 21–89% (median 53%) at 1 year and 37–68% (median 40%) at 2 years. Ten studies of zoledronic acid reported persistence rates of 34–73% (median 42%) for second dose and 20–54% (median 35.8%) for third dose. Ten studies of ibandronate adherence reported and 2-year persistence rates of 31–58% (median 47.5%) in 1 year and 13–35% (median 25%) at 2 years, and adherence rates of 21–72% (median 47.3%) and 15–58% (median 36.5%) respectively. Denosumab was reported in 19 studies, with second (1 year) and fourth (2 year) dose persistence rates of 61–100% (median 81%) and 36–99% (median 45.5%). There is substantial heterogeneity in reports of persistence and adherence rates with parenteral osteoporosis therapies. Most of the published data are from short-term studies and evaluations of long-term adherence and persistence with parenteral therapies for osteoporosis are needed.

Available only for authorised users

Compston JE, McClung MR, Leslie WD (2019) Osteoporosis. Lancet 393:364–376. https://doi.org/10.1016/S0140-6736(18)32112-3CrossRefPubMed

Johnell O, Kanis JA (2006) An estimate of the worldwide prevalence and disability associated with osteoporotic fractures. Osteoporos Int 17:1726–1733. https://doi.org/10.1007/s00198-006-0172-4CrossRefPubMed

Burge R, Dawson-Hughes B, Solomon DH et al (2007) Incidence and economic burden of osteoporosis-related fractures in the United States, 2005-2025. J Bone Miner Res 22:465–475. https://doi.org/10.1359/jbmr.061113CrossRefPubMed

Odén A, McCloskey EV, Johansson H, Kanis JA (2013) Assessing the impact of osteoporosis on the burden of hip fractures. Calcif Tissue Int 92:42–49. https://doi.org/10.1007/s00223-012-9666-6CrossRefPubMed

Hernlund E, Svedbom A, Ivergård M et al (2013) Osteoporosis in the European Union: medical management, epidemiology and economic burden. Arch Osteoporos 8:136. https://doi.org/10.1007/s11657-013-0136-1CrossRefPubMedPubMedCentral

Coyle D (2019) Cost-effectiveness of pharmacological treatments for osteoporosis consistent with the revised economic evaluation guidelines for Canada. MDM Policy Pract 4:1–16. https://doi.org/10.1177/2381468318818843CrossRef

Imaz I, Zegarra P, González-Enríquez J et al (2010) Poor bisphosphonate adherence for treatment of osteoporosis increases fracture risk: systematic review and meta-analysis. Osteoporos Int 21:1943–1951. https://doi.org/10.1007/s00198-009-1134-4CrossRefPubMed

Hubbard T, Paradis R (2015) Real world evidence: executive summary a new era for health care innovation. Netw Excell Heal Innov:1–19

Kothawala P, Badamgarav E, Ryu S et al (2007) Systematic review and meta-analysis of real-world adherence to drug therapy for osteoporosis. Mayo Clin Proc 82:1493–1501. https://doi.org/10.1016/S0025-6196(11)61093-8CrossRefPubMed

10.

Garber MC, Nau DP, Erickson SR et al (2004) The concordance of self-report with other measures of medication adherence. Med Care 42:649–652. https://doi.org/10.1097/01.mlr.0000129496.05898.02CrossRefPubMed

11.

Emkey RD, Ettinger M (2006) Improving compliance and persistence with bisphosphonate therapy for osteoporosis. Am J Med 119:S18–S24. https://doi.org/10.1016/j.amjmed.2005.12.019CrossRefPubMed

12.

Fatoye F, Smith P, Gebrye T, Yeowell G (2019) Real-world persistence and adherence with oral bisphosphonates for osteoporosis: a systematic review. BMJ Open 9:1–18. https://doi.org/10.1136/bmjopen-2018-027049CrossRef

13.

Kanis JA, Cooper C, Hiligsmann M et al (2011) Partial adherence: a new perspective on health economic assessment in osteoporosis. Osteoporos Int 22:2565–2573. https://doi.org/10.1007/s00198-011-1668-0CrossRefPubMed

14.

Stang A (2010) Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol 25:603–605. https://doi.org/10.1007/s10654-010-9491-zCrossRefPubMed

15.

Cramer JA, Roy A, Burrell A et al (2008) Medication compliance and persistence: terminology and definitions. Value Health 11:44–47. https://doi.org/10.1111/j.1524-4733.2007.00213.xCrossRefPubMed

16.

Barendregt JJ, Doi SA, Lee YY et al (2013) Meta-analysis of prevalence. J Epidemiol Community Health 67:974–978. https://doi.org/10.1136/jech-2013-203104CrossRefPubMed

17.

DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7:177–188. https://doi.org/10.1016/0197-2456(86)90046-2CrossRefPubMed

18.

Foster SA, Foley KA, Meadows ES et al (2011) Adherence and persistence with teriparatide among patients with commercial, Medicare, and Medicaid insurance. Osteoporos Int 22:551–557. https://doi.org/10.1007/s00198-010-1297-zCrossRefPubMed

19.

Yu SF, Yang TS, Chiu WC et al (2013) Non-adherence to anti-osteoporotic medications in Taiwan: physician specialty makes a difference. J Bone Miner Metab 31:351–359. https://doi.org/10.1007/s00774-013-0424-2CrossRefPubMed

20.

Burge R, Sato M, Sugihara T (2016) Real-world clinical and economic outcomes for daily teriparatide patients in Japan. J Bone Miner Metab 34:692–702. https://doi.org/10.1007/s00774-015-0720-0CrossRefPubMed

21.

Eliasaf A, Amitai A, Maram Edry M et al (2016) Compliance, persistence, and preferences regarding osteoporosis treatment during active therapy or drug holiday. J Clin Pharmacol 56:1416–1422. https://doi.org/10.1002/jcph.738CrossRefPubMed

22.

Chan DC, Chang CHC, Lim LC et al (2016) Association between teriparatide treatment persistence and adherence, and fracture incidence in Taiwan: analysis using the National Health Insurance Research Database. Osteoporos Int 27:2855–2865. https://doi.org/10.1007/s00198-016-3611-xCrossRefPubMedPubMedCentral

23.

Burge RT, Disch DP, Gelwicks S et al (2017) Hip and other fragility fracture incidence in real-world teriparatide-treated patients in the United States. Osteoporos Int 28:799–809. https://doi.org/10.1007/s00198-016-3888-9CrossRefPubMed

24.

Durden E, Pinto L, Lopez-Gonzalez L et al (2017) Two-year persistence and compliance with osteoporosis therapies among postmenopausal women in a commercially insured population in the United States. Arch Osteoporos 12:3–11. https://doi.org/10.1007/s11657-017-0316-5CrossRef

25.

Keshishian A, Boytsov N, Burge R et al (2017) Examining the effect of medication adherence on risk of subsequent fracture among women with a fragility fracture in the U.S. Medicare Population. J Manag Care Spec Pharm 23:1178–1190. https://doi.org/10.18553/jmcp.2017.17054CrossRefPubMed

26.

Ziller V, Kostev K, Kyvernitakis I et al (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 50:315–322. https://doi.org/10.5414/CP201632CrossRefPubMed

27.

Hazel-Fernandez L, Louder AM, Foster SA et al (2013) Association of teriparatide adherence and persistence with clinical and economic outcomes in Medicare Part D recipients: a retrospective cohort study. BMC Musculoskelet Disord 14:4. https://doi.org/10.1186/1471-2474-14-4CrossRefPubMedPubMedCentral

28.

Zhao Y, Johnston SS, Smith DM et al (2013) Association between teriparatide adherence and healthcare utilization and costs in real-world US kyphoplasty/vertebroplasty patients. Osteoporos Int 24:2525–2533. https://doi.org/10.1007/s00198-013-2324-7CrossRefPubMed

29.

Tomková S, Telepková D, Vaňuga P et al (2014) Therapeutic adherence to osteoporosis treatment. Int J Clin Pharmacol Ther 52:663–668. https://doi.org/10.5414/CP202072CrossRefPubMed

30.

Bonafede MM, Shi N, Bower AG et al (2015) Teriparatide treatment patterns in osteoporosis and subsequent fracture events: a US claims analysis. Osteoporos Int 26:1203–1212. https://doi.org/10.1007/s00198-014-2971-3CrossRefPubMedPubMedCentral

31.

Modi A, Siris ES, Tang J, Sen S (2015) Cost and consequences of noncompliance with osteoporosis treatment among women initiating therapy. Curr Med Res Opin 31:757–765. https://doi.org/10.1185/03007995.2015.1016605CrossRefPubMed

32.

Cheng LI, Durden E, Limone B et al (2015) Persistance and compliance with osteroporosis therapies among women in a commercially insured population in the United States. J Manag Care Pharm 21:824–833. https://doi.org/10.18553/jmcp.2015.21.9.824CrossRef

33.

Thorsteinsson A-L, Vestergaard P, Eiken P (2015) Compliance and persistence with treatment with parathyroid hormone for osteoporosis. A Danish national register-based cohort study. Arch Osteoporos 10:35. https://doi.org/10.1007/s11657-015-0237-0CrossRefPubMed

34.

Arden NK, Earl S, Fisher DJ et al (2006) Persistence with teriparatide in patients with osteoporosis: the UK experience. Osteoporos Int 17:1626–1629. https://doi.org/10.1007/s00198-006-0171-5CrossRefPubMed

35.

Landfeldt E, Ström O, Robbins S, Borgström F (2012) Adherence to treatment of primary osteoporosis and its association to fractures-the Swedish Adherence Register Analysis (SARA). Osteoporos Int 23:433–443. https://doi.org/10.1007/s00198-011-1549-6CrossRefPubMed

36.

Xu Y, Viswanathan HN, Ward MA et al (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 19:50–59. https://doi.org/10.1111/j.1365-2753.2011.01766.xCrossRefPubMed

37.

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 24:2079–2097. https://doi.org/10.1007/s00198-012-2221-5CrossRefPubMed

38.

Rajzbaum G, Grados F, Evans D et al (2014) Treatment persistence and changes in fracture risk, back pain, and quality of life amongst patients treated with teriparatide in routine clinical care in France: results from the European Forsteo Observational Study. Jt Bone Spine 81:69–75. https://doi.org/10.1016/j.jbspin.2013.05.001CrossRef

39.

Hadji P, Klein S, Haüssler B et al (2013) The bone evaluation study (BEST): patient care and persistence to treatment of osteoporosis in Germany. Int J Clin Pharmacol Ther 51:868–872. https://doi.org/10.5414/CP201931CrossRefPubMed

40.

Balasubramanian A, Goli BA, Critchlow C (2013) Discontinuation and reinitiation patterns of osteoporosis treatment among commercially insured postmenopausal women. Int J Gen Med 6:839. https://doi.org/10.2147/IJGM.S36944CrossRefPubMedPubMedCentral

41.

Kyvernitakis I, Kostev K, Kurth A et al (2014) Differences in persistency with teriparatide in patients with osteoporosis according to gender and health care provider. Osteoporos Int 25:2721–2728. https://doi.org/10.1007/s00198-014-2810-6CrossRefPubMed

42.

Carbonell-Abella C, Pages-Castella A, Javaid MK et al (2015) Early (1-year) discontinuation of different anti-osteoporosis medications compared: a population-based cohort study. Calcif Tissue Int 97:535–541. https://doi.org/10.1007/s00223-015-0040-3CrossRefPubMed

43.

Belhassen M, Confavreux CB, Cortet B et al (2017) Anti-osteoporotic treatments in France: initiation, persistence and switches over 6 years of follow-up. Osteoporos Int 28:853–862. https://doi.org/10.1007/s00198-016-3789-yCrossRefPubMed

44.

Modi A, Sajjan S, Insinga R et al (2017) Frequency of discontinuation of injectable osteoporosis therapies in US patients over 2 years. Osteoporos Int 28:1355–1363. https://doi.org/10.1007/s00198-016-3886-yCrossRefPubMed

45.

Martín-Merino E, Huerta-Álvarez C, Prieto-Alhambra D, Montero-Corominas D (2017) Cessation rate of anti-osteoporosis treatments and risk factors in Spanish primary care settings: a population-based cohort analysis. Arch Osteoporos 12:39. https://doi.org/10.1007/s11657-017-0331-6CrossRefPubMed

46.

Reyes C, Tebe C, Martinez-Laguna D et al (2017) One and two-year persistence with different anti-osteoporosis medications: a retrospective cohort study. Osteoporos Int 28:2997–3004. https://doi.org/10.1007/s00198-017-4144-7CrossRefPubMed

47.

Curtis JR, Yun H, Matthews R et al (2012) Adherence with intravenous zoledronate and intravenous ibandronate in the United States Medicare population. Arthritis Care Res 64:1054–1060. https://doi.org/10.1002/acr.21638CrossRef

48.

Hadji P, Kyvernitakis I, Kann PH et al (2016) GRAND-4: the German retrospective analysis of long-term persistence in women with osteoporosis treated with bisphosphonates or denosumab. Osteoporos Int 27:2967–2978. https://doi.org/10.1007/s00198-016-3623-6CrossRefPubMedPubMedCentral

49.

Lakatos P, Takács I, Marton I et al (2016) A retrospective longitudinal database study of persistence and compliance with treatment of osteoporosis in Hungary. Calcif Tissue Int 98:215–225. https://doi.org/10.1007/s00223-015-0082-6CrossRefPubMed

50.

Tremblay É, Perreault S, Dorais M (2016) Persistence with denosumab and zoledronic acid among older women: a population-based cohort study. Arch Osteoporos 11:30. https://doi.org/10.1007/s11657-016-0282-3CrossRefPubMed

51.

Hadji P, Papaioannou N, Gielen E 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 26:2479–2489. https://doi.org/10.1007/s00198-015-3164-4CrossRefPubMedPubMedCentral

52.

Fuksa L, Vytrisalova M (2015) Adherence to denosumab in the treatment of osteoporosis and its utilization in the Czech Republic. Curr Med Res Opin 31:1645–1653. https://doi.org/10.1185/03007995.2015.1065241CrossRefPubMed

53.

Karlsson L, Lundkvist J, Psachoulia E et al (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 26:2401–2411. https://doi.org/10.1007/s00198-015-3253-4CrossRefPubMedPubMedCentral

54.

Migliaccio S, Francomano D, Romagnoli E et al (2017) Persistence with denosumab therapy in women affected by osteoporosis with fragility fractures: a multicenter observational real practice study in Italy. J Endocrinol Investig 40:1321–1326. https://doi.org/10.1007/s40618-017-0701-3CrossRef

55.

Fahrleitner-Pammer A, Papaioannou N, Gielen E et al (2017) Factors associated with high 24-month persistence with denosumab: results of a real-world, non-interventional study of women with postmenopausal osteoporosis in Germany, Austria, Greece, and Belgium. Arch Osteoporos 12:58. https://doi.org/10.1007/s11657-017-0351-2CrossRefPubMedPubMedCentral

56.

Petranova T, Boyanov M, Shinkov A et al (2018) Medication-taking behaviour in Bulgarian women with postmenopausal osteoporosis treated with denosumab or monthly oral bisphosphonates. Arch Osteoporos 13:1. https://doi.org/10.1007/s11657-017-0413-5CrossRef

57.

Silverman SL, Siris E, Kendler DL et al (2014) Persistence at 12 months with denosumab in postmenopausal women with osteoporosis: interim results from a prospective observational study. Osteoporos Int 26:361–372. https://doi.org/10.1007/s00198-014-2871-6CrossRefPubMedPubMedCentral

58.

Cramer JA, Gold DT, Silverman SL, Lewiecki EM (2007) A systematic review of persistence and compliance with bisphosphonates for osteoporosis. Osteoporos Int 18:1023–1031. https://doi.org/10.1007/s00198-006-0322-8CrossRefPubMed

59.

Curtis JR, Westfall AO, Cheng H et al (2008) Benefit of adherence with bisphosphonates depends on age and fracture type: results from an analysis of 101,038 new bisphosphonate users. J Bone Miner Res 23:1435–1441. https://doi.org/10.1359/jbmr.080418CrossRefPubMedPubMedCentral

60.

Cook PF, Emiliozzi S, McCabe MM (2007) Telephone counseling to improve osteoporosis treatment adherence: an effectiveness study in community practice settings. Am J Med Qual 22:445–456. https://doi.org/10.1177/1062860607307990CrossRefPubMed

61.

McHorney CA, Schousboe JT, Cline RR, Weiss TW (2007) The impact of osteoporosis medication beliefs and side-effect experiences on non-adherence to oral bisphosphonates. Curr Med Res Opin 23:3137–3152. https://doi.org/10.1185/030079907X242890CrossRefPubMed

62.

Gomes DC, Costa-Paiva L, Farhat FCLG et al (2011) Ability to follow anti-reabsorptive drug treatment in postmenopausal women with reduced bone mass. Menopause 18:531–536. https://doi.org/10.1097/gme.0b013e3181fda7e7CrossRefPubMed

63.

Kerse N, Buetow S, Mainous AG et al (2004) Physician-patient relationship and medication compliance: a primary care investigation. Ann Fam Med 2:455–461CrossRefPubMedPubMedCentral

64.

Yeam CT, Chia S, Tan HCC et al (2018) A systematic review of factors affecting medication adherence among patients with osteoporosis. Osteoporos Int 29:2623–2637. https://doi.org/10.1007/s00198-018-4759-3CrossRefPubMed

65.

Basu S, Andrews J, Kishore S et al (2012) Comparative performance of private and public healthcare systems in low- and middle-income countries: a systematic review. PLoS Med 9:19. https://doi.org/10.1371/journal.pmed.1001244CrossRef

Title: Persistence and adherence to parenteral osteoporosis therapies: a systematic review
Authors: G. Koller
V. Goetz
B. Vandermeer
J. Homik
F. A. McAlister
D. Kendler
C. Ye
Publication date: 01-11-2020
Publisher: Springer London
Keywords: Osteoporosis
Osteoporosis
Denosumab
Ibandronate
Zoledronic Acid
Denosumab
Published in: Osteoporosis International / Issue 11/2020
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI: https://doi.org/10.1007/s00198-020-05507-9

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Persistence and adherence to parenteral osteoporosis therapies: a systematic review

Abstract

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 11/2020

A novel de novo heterozygous ALPL nonsense mutation associated with adult hypophosphatasia

Determinants of imminent fracture risk in postmenopausal women with osteoporosis

Effects of progesterone therapy on serum sclerostin levels in healthy menopausal women: a 3-month randomized, placebo-controlled clinical trial

Impact of an orthogeriatrician on length of stay of elderly patient with hip fracture

Comparative risk of osteoporotic fracture among patients with rheumatoid arthritis receiving TNF inhibitors versus other biologics: a cohort study

Correction to Effect of vitamin K on bone mineral density and fractures in adults: an updated systematic review and meta-analysis of randomised controlled trials