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Persistence and adherence to parenteral osteoporosis therapies: a systematic review

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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.

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References

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

    Article  CAS  PubMed  Google Scholar 

  2. 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/s00198-006-0172-4

    Article  CAS  PubMed  Google Scholar 

  3. 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.061113

    Article  PubMed  Google Scholar 

  4. 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/s00223-012-9666-6

    Article  CAS  PubMed  Google Scholar 

  5. 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/s11657-013-0136-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. 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/10.1177/2381468318818843

    Article  Google Scholar 

  7. 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/s00198-009-1134-4

    Article  CAS  PubMed  Google Scholar 

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

  9. 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)61093-8

    Article  PubMed  Google Scholar 

  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.0000129496.05898.02

    Article  PubMed  Google Scholar 

  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.2005.12.019

    Article  CAS  PubMed  Google Scholar 

  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-2018-027049

    Article  Google Scholar 

  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/s00198-011-1668-0

    Article  CAS  PubMed  Google Scholar 

  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-z

    Article  PubMed  Google Scholar 

  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.x

    Article  PubMed  Google Scholar 

  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-2013-203104

    Article  PubMed  Google Scholar 

  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)90046-2

    Article  CAS  PubMed  Google Scholar 

  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-z

    Article  CAS  PubMed  Google Scholar 

  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/s00774-013-0424-2

    Article  PubMed  Google Scholar 

  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/s00774-015-0720-0

    Article  PubMed  Google Scholar 

  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.738

    Article  CAS  PubMed  Google Scholar 

  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-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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/s00198-016-3888-9

    Article  CAS  PubMed  Google Scholar 

  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/s11657-017-0316-5

    Article  Google Scholar 

  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.2017.17054

    Article  PubMed  Google Scholar 

  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/CP201632

    Article  CAS  PubMed  Google Scholar 

  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/10.1186/1471-2474-14-4

    Article  PubMed  PubMed Central  Google Scholar 

  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/s00198-013-2324-7

    Article  CAS  PubMed  Google Scholar 

  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/CP202072

    Article  PubMed  Google Scholar 

  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/s00198-014-2971-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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/10.1185/03007995.2015.1016605

    Article  PubMed  Google Scholar 

  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.2015.21.9.824

    Article  Google Scholar 

  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/s11657-015-0237-0

    Article  PubMed  Google Scholar 

  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/s00198-006-0171-5

    Article  CAS  PubMed  Google Scholar 

  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/s00198-011-1549-6

    Article  CAS  PubMed  Google Scholar 

  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.x

    Article  PubMed  Google Scholar 

  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/s00198-012-2221-5

    Article  CAS  PubMed  Google Scholar 

  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.2013.05.001

    Article  CAS  Google Scholar 

  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/CP201931

    Article  PubMed  Google Scholar 

  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.S36944

    Article  PubMed  PubMed Central  Google Scholar 

  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/s00198-014-2810-6

    Article  CAS  PubMed  Google Scholar 

  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/s00223-015-0040-3

    Article  CAS  PubMed  Google Scholar 

  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-y

    Article  CAS  PubMed  Google Scholar 

  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-y

    Article  CAS  PubMed  Google Scholar 

  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/s11657-017-0331-6

    Article  PubMed  Google Scholar 

  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/s00198-017-4144-7

    Article  CAS  PubMed  Google Scholar 

  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.21638

    Article  CAS  Google Scholar 

  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/s00198-016-3623-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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/s00223-015-0082-6

    Article  CAS  PubMed  Google Scholar 

  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/s11657-016-0282-3

    Article  PubMed  Google Scholar 

  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/s00198-015-3164-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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/10.1185/03007995.2015.1065241

    Article  CAS  PubMed  Google Scholar 

  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/s00198-015-3253-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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/s40618-017-0701-3

    Article  CAS  Google Scholar 

  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/s11657-017-0351-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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/s11657-017-0413-5

    Article  Google Scholar 

  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/s00198-014-2871-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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/s00198-006-0322-8

    Article  CAS  PubMed  Google Scholar 

  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.080418

    Article  PubMed  PubMed Central  Google Scholar 

  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/10.1177/1062860607307990

    Article  PubMed  Google Scholar 

  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/10.1185/030079907X242890

    Article  CAS  PubMed  Google Scholar 

  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.0b013e3181fda7e7

    Article  PubMed  Google Scholar 

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

    Article  PubMed  PubMed Central  Google Scholar 

  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/s00198-018-4759-3

    Article  CAS  PubMed  Google Scholar 

  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.1001244

    Article  Google Scholar 

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Authors and Affiliations

  1. Department of Medicine, Division of Rheumatology, University of Alberta, 8-130 Clinical Sciences Building, 11350 83rd Avenue NW, Edmonton, AB, T6G 2G3, Canada

    G. Koller, V. Goetz, J. Homik & C. Ye

  2. Alberta Research Centre for Health Evidence, Biostatistician, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada

    B. Vandermeer

  3. Department of Medicine, Division of General Internal Medicine, University of Alberta, Edmonton, AB, Canada

    F. A. McAlister

  4. Department of Medicine, Division of Endocrinology, University of British Columbia, Vancouver, BC, Canada

    D. Kendler

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  1. G. Koller
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Koller, G., Goetz, V., Vandermeer, B. et al. Persistence and adherence to parenteral osteoporosis therapies: a systematic review. Osteoporos Int 31, 2093–2102 (2020). https://doi.org/10.1007/s00198-020-05507-9

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