Osteoporosis International

, Volume 29, Issue 12, pp 2623–2637 | Cite as

A systematic review of factors affecting medication adherence among patients with osteoporosis

  • C. T. Yeam
  • S. Chia
  • H. C. C. Tan
  • Y. H. Kwan
  • W. Fong
  • J. J. B. SengEmail author
Review Article



The aim of this review was to identify factors that influence patients’ adherence to anti-osteoporotic therapy. Factors identified that were associated with poorer medication adherence included polypharmacy, older age, and misconceptions about osteoporosis. Physicians need to be aware of these factors so as to optimize therapeutic outcomes for patients.


To identify factors that influence patients’ adherence to anti-osteoporotic therapy.


A systematic review of literature was performed for articles published up till January 2018 using PubMed®, PsychINFO®, Embase®, and CINAHL®. Peer-reviewed articles which examined factors associated with anti-osteoporotic medication adherence were included. Classes of anti-osteoporotic therapy included bisphosphonates, parathyroid hormone-related analogue, denosumab, selective estrogen receptor modulators, estrogen/progestin therapy, calcitonin, and strontium ranelate. Meta-analyses, case reports/series, and other systematic reviews were excluded. Identified factors were classified using the World Health Organization’s five dimensions of medication adherence (condition, patient, therapy, health-system, and socio-economic domains).


Of 2404 articles reviewed, 124 relevant articles were identified. The prevalence of medication adherence ranged from 12.9 to 95.4%. Twenty-four factors with 139 sub-factors were identified. Bisphosphonates were the most well-studied class of medication (n = 59, 48%). Condition-related factors that were associated with poorer medication adherence included polypharmacy, and history of falls was associated with higher medication adherence. Patient-related factors which were associated with poorer medication adherence included older age and misconceptions about osteoporosis while therapy-related factors included higher dosing frequency and medication side effects. Health system-based factors associated with poorer medication adherence included care under different medical specialties and lack of patient education. Socio-economic-related factors associated with poorer medication adherence included current smoker and lack of medical insurance coverage.


This review identified factors associated with poor medication adherence among osteoporotic patients. To optimize therapeutic outcomes for patients, clinicians need to be aware of the complexity of factors affecting medication adherence.


Anti-osteoporotic therapy Medication adherence Osteoporosis Patient compliance Bisphosphonates 



This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Compliance with ethical standards

Conflicts of interest


Supplementary material

198_2018_4759_MOESM1_ESM.docx (65 kb)
ESM 1 (DOCX 64 kb)


  1. 1.
    Wright NC, Looker AC, Saag KG, Curtis JR, Delzell ES, Randall S, Dawson-Hughes B (2014) The recent prevalence of osteoporosis and low bone mass in the United States based on bone mineral density at the femoral neck or lumbar spine. J Bone Miner Res 29(11):2520–2526. CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Johnell O, Kanis JA (2006) An estimate of the worldwide prevalence and disability associated with osteoporotic fractures. Osteoporos Int 17(12):1726–1733. CrossRefPubMedGoogle Scholar
  3. 3.
    Gullberg B, Johnell O, Kanis JA (1997) World-wide projections for hip fracture. Osteoporos Int 7(5):407–413CrossRefGoogle Scholar
  4. 4.
    Mikyas Y, Agodoa I, Yurgin N (2014) A systematic review of osteoporosis medication adherence and osteoporosis-related fracture costs in men. Appl Health Econ Health Policy 12(3):267–277. CrossRefPubMedGoogle Scholar
  5. 5.
    Borgstrom F, Zethraeus N, Johnell O, Lidgren L, Ponzer S, Svensson O, Abdon P, Ornstein E, Lunsjo K, Thorngren KG, Sernbo I, Rehnberg C, Jonsson B (2006) Costs and quality of life associated with osteoporosis-related fractures in Sweden. Osteoporos Int 17(5):637–650. CrossRefPubMedGoogle Scholar
  6. 6.
    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(7):2079–2097. CrossRefPubMedGoogle Scholar
  7. 7.
    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(12):3137–3152. CrossRefPubMedGoogle Scholar
  8. 8.
    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(9):1453–1460. CrossRefPubMedGoogle Scholar
  9. 9.
    Weycker D, Macarios D, Edelsberg J, Oster G (2006) Compliance with drug therapy for postmenopausal osteoporosis. Osteoporos Int 17(11):1645–1652. CrossRefPubMedGoogle Scholar
  10. 10.
    Gomes DC, Costa-Paiva L, Farhat FC, Pedro AO, Pinto-Neto AM (2011) Ability to follow anti-reabsorptive drug treatment in postmenopausal women with reduced bone mass. Menopause 18(5):531–536. CrossRefPubMedGoogle Scholar
  11. 11.
    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(6):445–456. CrossRefPubMedGoogle Scholar
  12. 12.
    Curtis JR, Westfall AO, Cheng H, Lyles K, Saag KG, Delzell E (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(9):1435–1441. CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    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(11):1943–1951. CrossRefPubMedGoogle Scholar
  14. 14.
    Burkhart PV, Sabate E (2003) Adherence to long-term therapies: evidence for action. J Nurs Scholarsh 35(3):207Google Scholar
  15. 15.
    Tasci I, Cintosun U, Safer U, Naharci MI, Bozoglu E, Aydogdu A, Doruk H (2017) Assessment of geriatric predictors of adherence to zoledronic acid treatment for osteoporosis: a prospective follow-up study. Acta Clin Belg:1–7. CrossRefGoogle Scholar
  16. 16.
    Yu SF, Yang TS, Chiu WC, Hsu CY, Chou CL, Su YJ, Lai HM, Chen YC, Chen CJ, Cheng TT (2013) Non-adherence to anti-osteoporotic medications in Taiwan: physician specialty makes a difference. J Bone Miner Metab 31(3):351–359. CrossRefPubMedGoogle Scholar
  17. 17.
    Fahrleitner-Pammer A, Papaioannou N, Gielen E, Feudjo Tepie M, Toffis C, Frieling I, Geusens P, Makras P, Boschitsch E, Callens J, Anastasilakis AD, Niedhart C, Resch H, Kalouche-Khalil L, Hadji P (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(1):58. CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Iwamoto J, Miyata A, Sato Y, Takeda T, Matsumoto H (2009) Factors affecting discontinuation of alendronate treatment in postmenopausal Japanese women with osteoporosis. J Chin Med Assoc 72(12):619–624. CrossRefPubMedGoogle Scholar
  19. 19.
    Yun H, Curtis JR, Guo L, Kilgore M, Muntner P, Saag K, Matthews R, Morrisey M, Wright NC, Becker DJ, Delzell E (2014) Patterns and predictors of osteoporosis medication discontinuation and switching among Medicare beneficiaries. BMC Musculoskelet Disord 15:112. CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Roerholt C, Eiken P, Abrahamsen B (2009) Initiation of anti-osteoporotic therapy in patients with recent fractures: a nationwide analysis of prescription rates and persistence. Osteopor Int 20(2):299–307. CrossRefGoogle Scholar
  21. 21.
    Palacios S, Sanchez-Borrego R, Neyro JL, Quereda F, Vazquez F, Perez M, Perez M (2009) Knowledge and compliance from patients with postmenopausal osteoporosis treatment. Menopause Int 15(3):113–119. CrossRefPubMedGoogle Scholar
  22. 22.
    Hadji P, Papaioannou N, Gielen E, Feudjo Tepie M, Zhang E, Frieling I, Geusens P, Makras P, Resch H, Moller G, Kalouche-Khalil L, Fahrleitner-Pammer A (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(10):2479–2489. CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Arden NK, Earl S, Fisher DJ, Cooper C, Carruthers S, Goater M (2006) Persistence with teriparatide in patients with osteoporosis: the UK experience. Osteoporos Int 17(11):1626–1629. CrossRefPubMedGoogle Scholar
  24. 24.
    Cheen MH, Kong MC, Zhang RF, Tee FM, Chandran M (2012) Adherence to osteoporosis medications amongst Singaporean patients. Osteoporos Int 23(3):1053–1060. CrossRefPubMedGoogle Scholar
  25. 25.
    Solomon DH, Avorn J, Katz JN, Finkelstein JS, Arnold M, Polinski JM, Brookhart MA (2005) Compliance with osteoporosis medications. Arch Intern Med 165(20):2414–2419. CrossRefPubMedGoogle Scholar
  26. 26.
    Rossini M, Bianchi G, Di Munno O, Giannini S, Minisola S, Sinigaglia L, Adami S (2006) Determinants of adherence to osteoporosis treatment in clinical practice. Osteoporos Int 17(6):914–921. CrossRefPubMedGoogle Scholar
  27. 27.
    Kyvernitakis I, Kostev K, Kurth A, Albert US, Hadji P (2014) Differences in persistency with teriparatide in patients with osteoporosis according to gender and health care provider. Osteoporos Int 25(12):2721–2728. CrossRefPubMedGoogle Scholar
  28. 28.
    Wade SW, Satram-Hoang S, Stolshek BS (2014) Long-term persistence and switching patterns among women using osteoporosis therapies: 24- and 36-month results from POSSIBLE US. Osteoporos Int 25(9):2279–2290. CrossRefPubMedGoogle Scholar
  29. 29.
    Dugard MN, Jones TJ, Davie MW (2010) Uptake of treatment for osteoporosis and compliance after bone density measurement in the community. J Epidemiol Community Health 64(6):518–522. CrossRefPubMedGoogle Scholar
  30. 30.
    Ziller V, Wetzel K, Kyvernitakis I, Seker-Pektas B, Hadji P (2011) Adherence and persistence in patients with postmenopausal osteoporosis treated with raloxifene. Climacteric 14(2):228–235. CrossRefPubMedGoogle Scholar
  31. 31.
    Penning-van Beest FJ, Erkens JA, Olson M, Herings RM (2008) Determinants of non-compliance with bisphosphonates in women with postmenopausal osteoporosis. Curr Med Res Opin 24(5):1337–1344. CrossRefPubMedGoogle Scholar
  32. 32.
    Modi A, Siris S, Yang X, Fan CP, Sajjan S (2015) Association between gastrointestinal events and persistence with osteoporosis therapy: analysis of administrative claims of a U.S. managed care population. J Manag Care Spec Pharm 21(6):499–506. CrossRefPubMedGoogle Scholar
  33. 33.
    Siris ES, Fan CS, Yang X, Sajjan S, Sen SS, Modi A (2016) Association between gastrointestinal events and compliance with osteoporosis therapy. Bone Rep 4:5–10. CrossRefPubMedGoogle Scholar
  34. 34.
    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(7):1005–1015. CrossRefPubMedGoogle Scholar
  35. 35.
    Papaioannou A, Ioannidis G, Adachi JD, Sebaldt RJ, Ferko N, Puglia M, Brown J, Tenenhouse A, Olszynski WP, Boulos P, Hanley DA, Josse R, Murray TM, Petrie A, Goldsmith CH (2003) Adherence to bisphosphonates and hormone replacement therapy in a tertiary care setting of patients in the CANDOO database. Osteoporos Int 14(10):808–813. CrossRefPubMedGoogle Scholar
  36. 36.
    Carr AJ, Thompson PW, Cooper C (2006) Factors associated with adherence and persistence to bisphosphonate therapy in osteoporosis: a cross-sectional survey. Osteoporos Int 17(11):1638–1644. CrossRefPubMedGoogle Scholar
  37. 37.
    Tanaka I, Sato M, Sugihara T, Faries DE, Nojiri S, Graham-Clarke P, Flynn JA, Burge RT (2013) Adherence and persistence with once-daily teriparatide in Japan: a retrospective, prescription database, cohort study. J Osteoporos 2013:654218. CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Lo JC, Pressman AR, Omar MA, Ettinger B (2006) Persistence with weekly alendronate therapy among postmenopausal women. Osteoporos Int 17(6):922–928. CrossRefPubMedGoogle Scholar
  39. 39.
    Abobului M, Berghea F, Vlad V, Balanescu A, Opris D, Bojinca V, Kosevoi Tichie A, Predeteanu D, Ionescu R (2015) Evaluation of adherence to anti-osteoporosis treatment from the socio-economic context. J Med Life 8(Spec Issue):119–123PubMedPubMedCentralGoogle Scholar
  40. 40.
    Roh YH, Koh YD, Noh JH, Gong HS, Baek GH (2017) Effect of health literacy on adherence to osteoporosis treatment among patients with distal radius fracture. Arch Osteoporos 12(1):42. CrossRefPubMedGoogle Scholar
  41. 41.
    Ringe JD, Christodoulakos GE, Mellstrom D, Petto H, Nickelsen T, Marin F, Pavo I (2007) Patient compliance with alendronate, risedronate and raloxifene for the treatment of osteoporosis in postmenopausal women. Curr Med Res Opin 23(11):2677–2687. CrossRefPubMedGoogle Scholar
  42. 42.
    Vestergaard P, Hermann AP, Gram J, Jensen LB, Kolthoff N, Abrahamsen B, Brot C, Eiken P (1997) Improving compliance with hormonal replacement therapy in primary osteoporosis prevention. Maturitas 28(2):137–145CrossRefGoogle Scholar
  43. 43.
    Solomon DH, Brookhart MA, Tsao P, Sundaresan D, Andrade SE, Mazor K, Yood R (2011) Predictors of very low adherence with medications for osteoporosis: towards development of a clinical prediction rule. Osteoporos Int 22(6):1737–1743. CrossRefPubMedGoogle Scholar
  44. 44.
    Tosteson AN, Do TP, Wade SW, Anthony MS, Downs RW (2010) Persistence and switching patterns among women with varied osteoporosis medication histories: 12-month results from POSSIBLE US. Osteoporos Int 21(10):1769–1780. CrossRefPubMedGoogle Scholar
  45. 45.
    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(1):145–155. CrossRefPubMedGoogle Scholar
  46. 46.
    Garcia-Sempere A, Hurtado I, Sanfelix-Genoves J, Rodriguez-Bernal CL, Gil Orozco R, Peiro S, Sanfelix-Gimeno G (2017) Primary and secondary non-adherence to osteoporotic medications after hip fracture in Spain. The PREV2FO population-based retrospective cohort study. Sci Rep 7(1):11784. CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    de Castro Gomes DA, Valadares AL, Pinto-Neto AM, Morais SS, Costa-Paiva L (2012) Ability to follow drug treatment with calcium and vitamin D in postmenopausal women with reduced bone mass. Menopause 19(9):989–994. CrossRefPubMedGoogle Scholar
  48. 48.
    Zanchetta JR, Hakim C, Lombas C (2004) Observational study of compliance and continuance rates of raloxifene in the prevention and treatment of osteoporosis. Curr Ther Res Clin Exp 65(6):470–480. CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Tandon VR, Sharma S, Mahajan S, Mahajan A, Khajuria V, Gillani Z (2014) First Indian prospective randomized comparative study evaluating adherence and compliance of postmenopausal osteoporotic patients for daily alendronate, weekly risedronate and monthly ibandronate regimens of bisphosphonates. J Midlife Health 5(1):29–33. CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Jacob L, Dreher M, Kostev K, Hadji P (2016) Increased treatment persistence and its determinants in women with osteoporosis with prior fracture compared to those without fracture. Osteoporos Int 27(3):963–969. CrossRefPubMedGoogle Scholar
  51. 51.
    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(2):236–242. CrossRefPubMedGoogle Scholar
  52. 52.
    Curtis JR, Xi J, Westfall AO, Cheng H, Lyles K, Saag KG, Delzell E (2009) Improving the prediction of medication compliance: the example of bisphosphonates for osteoporosis. Med Care 47(3):334–341. CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    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(9):2193–2203. CrossRefPubMedGoogle Scholar
  54. 54.
    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(10):1686–1694. CrossRefPubMedGoogle Scholar
  55. 55.
    Reynolds K, Muntner P, Cheetham TC, Harrison TN, Morisky DE, Silverman S, Gold DT, Vansomphone SS, Wei R, O'Malley CD (2013) Primary non-adherence to bisphosphonates in an integrated healthcare setting. Osteoporos Int 24(9):2509–2517. CrossRefPubMedGoogle Scholar
  56. 56.
    Modi A, Sen S, Adachi JD, Adami S, Cortet B, Cooper AL, Geusens P, Mellstrom D, Weaver JP, van den Bergh JP, Keown P, Sajjan S (2017) The impact of GI events on persistence and adherence to osteoporosis treatment: 3-, 6-, and 12-month findings in the MUSIC-OS study. Osteoporos Int. CrossRefGoogle Scholar
  57. 57.
    Castelo-Branco C, Cortes X, Ferrer M (2010) Treatment persistence and compliance with a combination of calcium and vitamin D. Climacteric 13(6):578–584. CrossRefPubMedGoogle Scholar
  58. 58.
    Silverman SL, Siris E, Kendler DL, Belazi D, Brown JP, Gold DT, Lewiecki EM, Papaioannou A, Simonelli C, Ferreira I, Balasubramanian A, Dakin P, Ho P, Siddhanti S, Stolshek B, Recknor C (2015) Persistence at 12 months with denosumab in postmenopausal women with osteoporosis: interim results from a prospective observational study. Osteoporos Int 26(1):361–372. CrossRefPubMedGoogle Scholar
  59. 59.
    Sanfelix-Genoves J, Gil-Guillen VF, Orozco-Beltran D, Giner-Ruiz V, Pertusa-Martinez S, Reig-Moya B, Carratala C (2009) Determinant factors of osteoporosis patients’ reported therapeutic adherence to calcium and/or vitamin D supplements: a cross-sectional, observational study of postmenopausal women. Drugs Aging 26(10):861–869. CrossRefPubMedGoogle Scholar
  60. 60.
    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 14:276. CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Park JH, Park EK, Koo DW, Lee S, Lee SH, Kim GT, Lee SG (2017) Compliance and persistence with oral bisphosphonates for the treatment of osteoporosis in female patients with rheumatoid arthritis. BMC Musculoskelet Disord 18(1):152. CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Jones TJ, Petrella RJ, Crilly R (2008) Determinants of persistence with weekly bisphosphonates in patients with osteoporosis. J Rheumatol 35(9):1865–1873PubMedGoogle Scholar
  63. 63.
    Briesacher BA, Andrade SE, Fouayzi H, Chan KA (2008) Comparison of drug adherence rates among patients with seven different medical conditions. Pharmacotherapy 28(4):437–443. CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Schousboe JT, Dowd BE, Davison ML, Kane RL (2010) Association of medication attitudes with non-persistence and non-compliance with medication to prevent fractures. Osteoporos Int 21(11):1899–1909. CrossRefPubMedGoogle Scholar
  65. 65.
    Wozniak LA, Johnson JA, McAlister FA, Beaupre LA, Bellerose D, Rowe BH, Majumdar SR (2017) Understanding fragility fracture patients' decision-making process regarding bisphosphonate treatment. Osteoporos Int 28(1):219–229. CrossRefPubMedGoogle Scholar
  66. 66.
    Richards JS, Cannon GW, Hayden CL, Amdur RL, Lazaro D, Mikuls TR, Reimold AM, Caplan L, Johnson DS, Schwab P, Cherascu BN, Kerr GS (2012) Adherence with bisphosphonate therapy in US veterans with rheumatoid arthritis. Arthritis Care Res 64(12):1864–1870. CrossRefGoogle Scholar
  67. 67.
    Foster SA, Foley KA, Meadows ES, Johnston JA, Wang SS, Pohl GM, Long SR (2011) Adherence and persistence with teriparatide among patients with commercial, Medicare, and Medicaid insurance. Osteoporos Int 22(2):551–557. CrossRefPubMedGoogle Scholar
  68. 68.
    Ideguchi H, Ohno S, Takase K, Ueda A, Ishigatsubo Y (2008) Outcomes after switching from one bisphosphonate to another in 146 patients at a single university hospital. Osteoporos Int 19(12):1777–1783. CrossRefPubMedGoogle Scholar
  69. 69.
    Ideguchi H, Ohno S, Hattori H, Ishigatsubo Y (2007) Persistence with bisphosphonate therapy including treatment courses with multiple sequential bisphosphonates in the real world. Osteoporos Int 18(10):1421–1427. CrossRefPubMedGoogle Scholar
  70. 70.
    Klop C, Welsing PM, Elders PJ, Overbeek JA, Souverein PC, Burden AM, van Onzenoort HA, Leufkens HG, Bijlsma JW, de Vries F (2015) Long-term persistence with anti-osteoporosis drugs after fracture. Osteoporos Int 26(6):1831–1840. CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    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(3):585–594. CrossRefPubMedGoogle Scholar
  72. 72.
    Curtis JR, Yun H, Matthews R, Saag KG, Delzell E (2012) Adherence with intravenous zoledronate and intravenous ibandronate in the United States Medicare population. Arthritis Care Res (Hoboken) 64(7):1054–1060. CrossRefGoogle Scholar
  73. 73.
    Hui RL, Adams AL, Niu F, Ettinger B, Yi DK, Chandra M, Lo JC (2017) Predicting adherence and persistence with oral bisphosphonate therapy in an integrated health care delivery system. J Manag Care Spec Pharm 23(4):503–512. CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    Segal E, Tamir A, Ish-Shalom S (2003) Compliance of osteoporotic patients with different treatment regimens. Isr Med Assoc J 5(12):859–862PubMedGoogle Scholar
  75. 75.
    Devold HM, Furu K, Skurtveit S, Tverdal A, Falch JA, Sogaard AJ (2012) Influence of socioeconomic factors on the adherence of alendronate treatment in incident users in Norway. Pharmacoepidemiol Drug Saf 21(3):297–304. CrossRefPubMedGoogle Scholar
  76. 76.
    Confavreux CB, Canoui-Poitrine F, Schott AM, Ambrosi V, Tainturier V, Chapurlat RD (2012) Persistence at 1 year of oral antiosteoporotic drugs: a prospective study in a comprehensive health insurance database. Eur J Endocrinol 166(4):735–741. CrossRefPubMedGoogle Scholar
  77. 77.
    Casula M, Catapano AL, Piccinelli R, Menditto E, Manzoli L, De Fendi L, Orlando V, Flacco ME, Gambera M, Filippi A, Tragni E (2014) Assessment and potential determinants of compliance and persistence to antiosteoporosis therapy in Italy. Am J Manag Care 20(5):e138–e145PubMedGoogle Scholar
  78. 78.
    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(5):562–570. CrossRefPubMedGoogle Scholar
  79. 79.
    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(5):1537–1546. CrossRefPubMedGoogle Scholar
  80. 80.
    Wu X, Wei D, Sun B, Wu XN (2016) Poor medication adherence to bisphosphonates and high self-perception of aging in elderly female patients with osteoporosis. Osteoporos Int 27(10):3083–3090. CrossRefPubMedGoogle Scholar
  81. 81.
    Goldshtein I, Rouach V, Shamir-Stein N, Yu J, Chodick G (2016) Role of side effects, physician involvement, and patient perception in non-adherence with oral bisphosphonates. Adv Ther 33(8):1374–1384. CrossRefPubMedGoogle Scholar
  82. 82.
    Lee YK, Nho JH, Ha YC, Koo KH (2012) Persistence with intravenous zoledronate in elderly patients with osteoporosis. Osteoporos Int 23(9):2329–2333. CrossRefPubMedGoogle Scholar
  83. 83.
    Sheehy O, Kindundu CM, Barbeau M, LeLorier J (2009) Differences in persistence among different weekly oral bisphosphonate medications. Osteoporos Int 20(8):1369–1376. CrossRefPubMedGoogle Scholar
  84. 84.
    Ganda K, Schaffer A, Pearson S, Seibel MJ (2014) Compliance and persistence to oral bisphosphonate therapy following initiation within a secondary fracture prevention program: a randomised controlled trial of specialist vs. non-specialist management. Osteoporos Int 25(4):1345–1355. CrossRefPubMedGoogle Scholar
  85. 85.
    Thorsteinsson AL, 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. CrossRefPubMedGoogle Scholar
  86. 86.
    Berecki-Gisolf J, Hockey R, Dobson A (2008) Adherence to bisphosphonate treatment by elderly women. Menopause 15(5):984–990. CrossRefPubMedGoogle Scholar
  87. 87.
    Huas D, Debiais F, Blotman F, Cortet B, Mercier F, Rousseaux C, Berger V, Gaudin A-F, Cotté F-E (2010) Compliance and treatment satisfaction of post menopausal women treated for osteoporosis. Compliance with osteoporosis treatment. BMC Womens Health 10:26–26. CrossRefPubMedPubMedCentralGoogle Scholar
  88. 88.
    Ziller V, Zimmermann SP, Kalder M, Ziller M, Seker-Pektas B, Hellmeyer L, Hadji P (2010) Adherence and persistence in patients with severe osteoporosis treated with teriparatide. Curr Med Res Opin 26(3):675–681. CrossRefPubMedGoogle Scholar
  89. 89.
    Kamatari M, Koto S, Ozawa N, Urao C, Suzuki Y, Akasaka E, Yanagimoto K, Sakota K (2007) Factors affecting long-term compliance of osteoporotic patients with bisphosphonate treatment and QOL assessment in actual practice: alendronate and risedronate. J Bone Miner Metab 25(5):302–309. CrossRefPubMedGoogle Scholar
  90. 90.
    Nielsen DS, Langdahl BL, Sorensen OH, Sorensen HA, Brixen KT (2010) Persistence to medical treatment of osteoporosis in women at three different clinical settings—a historical cohort study. Scand J Public Health 38(5):502–507. CrossRefPubMedGoogle Scholar
  91. 91.
    Orimo H, Sato M, Kimura S, Wada K, Chen X, Yoshida S, Crawford B (2017) Understanding the factors associated with initiation and adherence of osteoporosis medication in Japan: an analysis of patient perceptions. Osteoporos Sarcopenia 3(4):174–184. CrossRefGoogle Scholar
  92. 92.
    Lindsay BR, Olufade T, Bauer J, Babrowicz J, Hahn R (2016) Patient-reported barriers to osteoporosis therapy. Arch Osteoporos 11:19. CrossRefPubMedPubMedCentralGoogle Scholar
  93. 93.
    Salter C, McDaid L, Bhattacharya D, Holland R, Marshall T, Howe A (2014) Abandoned acid? Understanding adherence to bisphosphonate medications for the prevention of osteoporosis among older women: a qualitative longitudinal study. PLoS One 9(1):e83552. CrossRefPubMedPubMedCentralGoogle Scholar
  94. 94.
    Iversen MD, Vora RR, Servi A, Solomon DH (2011) Factors affecting adherence to osteoporosis medications: a focus group approach examining viewpoints of patients and providers. Journal of geriatric physical therapy (2001) 34(2):72–81. CrossRefGoogle Scholar
  95. 95.
    Hall SF, Edmonds SW, Lou Y, Cram P, Roblin DW, Saag KG, Wright NC, Jones MP, Wolinsky FD (2017) Patient-reported reasons for nonadherence to recommended osteoporosis pharmacotherapy. J Am Pharm Assoc (2003) 57(4):503–509. CrossRefGoogle Scholar
  96. 96.
    Brask-Lindemann D, Cadarette SM, Eskildsen P, Abrahamsen B (2011) Osteoporosis pharmacotherapy following bone densitometry: importance of patient beliefs and understanding of DXA results. Osteoporos Int 22(5):1493–1501. CrossRefPubMedGoogle Scholar
  97. 97.
    Lewiecki EM, Babbitt AM, Piziak VK, Ozturk ZE, Bone HG (2008) Adherence to and gastrointestinal tolerability of monthly oral or quarterly intravenous ibandronate therapy in women with previous intolerance to oral bisphosphonates: a 12-month, open-label, prospective evaluation. Clin Ther 30(4):605–621CrossRefGoogle Scholar
  98. 98.
    Kertes J, Dushenat M, Vesterman JL, Lemberger J, Bregman J, Friedman N (2008) Factors contributing to compliance with osteoporosis medication. Isr Med Assoc J 10(3):207–213PubMedGoogle Scholar
  99. 99.
    Blotman F, Cortet B, Hilliquin P, Avouac B, Allaert FA, Pouchain D, Gaudin AF, Cotte FE, El Hasnaoui A (2007) Characterisation of patients with postmenopausal osteoporosis in French primary healthcare. Drugs Aging 24(7):603–614CrossRefGoogle Scholar
  100. 100.
    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(8):1268–1274. CrossRefPubMedGoogle Scholar
  101. 101.
    Ettinger B (1998) Alendronate use among 812 women: prevalence of gastrointestinal complaints, noncompliance with patient instructions, and discontinuation. J Manag Care Pharm 4(5):488–492. CrossRefGoogle Scholar
  102. 102.
    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(7):1249–1256. CrossRefPubMedGoogle Scholar
  103. 103.
    Tomkova S, Telepkova D, Vanuga P, Killinger Z, Sulkova I, Celec P, Payer J (2014) Therapeutic adherence to osteoporosis treatment. Int J Clin Pharmacol Ther 52(8):663–668. CrossRefPubMedGoogle Scholar
  104. 104.
    Recker RR, Gallagher R, MacCosbe PE (2005) Effect of dosing frequency on bisphosphonate medication adherence in a large longitudinal cohort of women. Mayo Clin Proc 80(7):856–861. CrossRefPubMedGoogle Scholar
  105. 105.
    Downey TW, Foltz SH, Boccuzzi SJ, Omar MA, Kahler KH (2006) Adherence and persistence associated with the pharmacologic treatment of osteoporosis in a managed care setting. South Med J 99(6):570–575. CrossRefPubMedGoogle Scholar
  106. 106.
    Kishimoto H, Maehara M (2015) Compliance and persistence with daily, weekly, and monthly bisphosphonates for osteoporosis in Japan: analysis of data from the CISA. Arch Osteoporos 10:231. CrossRefPubMedGoogle Scholar
  107. 107.
    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(8):1831–1839. CrossRefPubMedGoogle Scholar
  108. 108.
    Gold DT, Safi W, Trinh H (2006) Patient preference and adherence: comparative US studies between two bisphosphonates, weekly risedronate and monthly ibandronate. Curr Med Res Opin 22(12):2383–2391. CrossRefPubMedGoogle Scholar
  109. 109.
    Hamilton B, McCoy K, Taggart H (2003) Tolerability and compliance with risedronate in clinical practice. Osteoporos Int 14(3):259–262. CrossRefPubMedGoogle Scholar
  110. 110.
    Lau E, Papaioannou A, Dolovich L, Adachi J, Sawka AM, Burns S, Nair K, Pathak A (2008) Patients’ adherence to osteoporosis therapy: exploring the perceptions of postmenopausal women. Can Fam Physician 54(3):394–402PubMedGoogle Scholar
  111. 111.
    Pasion EG, Sivananthan SK, Kung AW, Chen SH, Chen YJ, Mirasol R, Tay BK, Shah GA, Khan MA, Tam F, Hall BJ, Thiebaud D (2007) Comparison of raloxifene and bisphosphonates based on adherence and treatment satisfaction in postmenopausal Asian women. J Bone Miner Metab 25(2):105–113. CrossRefPubMedGoogle Scholar
  112. 112.
    Conti F, Piscitelli P, Italiano G, Parma A, Caffetti MC, Giolli L, Di Tanna GL, Guazzini A, Brandi ML (2012) Adherence to calcium and vitamin D supplementations: results from the ADVICE survey. Clin Cases Miner Bone Metab 9(3):157–160PubMedPubMedCentralGoogle Scholar
  113. 113.
    Modi A, Sen S, Adachi JD, Adami S, Cortet B, Cooper AL, Geusens P, Mellstrom D, Weaver J, van den Bergh JP, Nguyen AM, Sajjan S (2016) Gastrointestinal symptoms and association with medication use patterns, adherence, treatment satisfaction, quality of life, and resource use in osteoporosis: baseline results of the MUSIC-OS study. Osteoporos Int 27(3):1227–1238. CrossRefPubMedGoogle Scholar
  114. 114.
    Vytrisalova M, Blazkova S, Palicka V, Vlcek J, Cejkova M, Hala T, Pavelka K, Koblihova H (2008) Self-reported compliance with osteoporosis medication-qualitative aspects and correlates. Maturitas 60(3–4):223–229. CrossRefPubMedGoogle Scholar
  115. 115.
    Zarowitz BJ, Cheng LI, Allen C, O'Shea T, Stolshek B (2015) Osteoporosis prevalence and characteristics of treated and untreated nursing home residents with osteoporosis. J Am Med Dir Assoc 16(4):341–348. CrossRefPubMedGoogle Scholar
  116. 116.
    Turbi C, Herrero-Beaumont G, Acebes JC, Torrijos A, Grana J, Miguelez R, Sacristan J, Marin F (2004) Compliance and satisfaction with raloxifene versus alendronate for the treatment of postmenopausal osteoporosis in clinical practice: an open-label, prospective, nonrandomized, observational study. Clin Ther 26(2):245–256CrossRefGoogle Scholar
  117. 117.
    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. CrossRefPubMedPubMedCentralGoogle Scholar
  118. 118.
    Steel SA, Albertazzi P, Howarth EM, Purdie DW (2003) Factors affecting long-term adherence to hormone replacement therapy after screening for osteoporosis. Climacteric 6(2):96–103CrossRefGoogle Scholar
  119. 119.
    Cooper A, Drake J, Brankin E (2006) Treatment persistence with once-monthly ibandronate and patient support vs. once-weekly alendronate: results from the PERSIST study. Int J Clin Pract 60(8):896–905. CrossRefPubMedPubMedCentralGoogle Scholar
  120. 120.
    Cheng LI, Durden E, Limone B, Radbill L, Juneau PL, Spangler L, Mirza FM, Stolshek BS (2015) Persistance and compliance with osteroporosis therapies among women in a commercially insured population in the United States. J Manag Care Spec Pharm 21(9):824–833, 833a. CrossRefPubMedGoogle Scholar
  121. 121.
    Strom O, Landfeldt E (2012) The association between automatic generic substitution and treatment persistence with oral bisphosphonates. Osteoporos Int 23(8):2201–2209. CrossRefPubMedGoogle Scholar
  122. 122.
    Ringe JD, Moller G (2009) Differences in persistence, safety and efficacy of generic and original branded once weekly bisphosphonates in patients with postmenopausal osteoporosis: 1-year results of a retrospective patient chart review analysis. Rheumatol Int 30(2):213–221. CrossRefPubMedGoogle Scholar
  123. 123.
    van der Zwaard BC, van Hout W, Hugtenburg JG, van der Horst HE, Elders PJM (2017) Adherence and persistence of patients using oral bone sparing drugs in primary care. Fam Pract 34(5):525–531. CrossRefPubMedGoogle Scholar
  124. 124.
    Papaioannou A, Khan A, Belanger A, Bensen W, Kendler D, Theoret F, Amin M, Brekke L, Erdmann M, Walker V, Adachi JD (2015) Persistence with denosumab therapy among osteoporotic women in the Canadian patient-support program. Curr Med Res Opin 31(7):1391–1401. CrossRefPubMedGoogle Scholar
  125. 125.
    Shehadeh-Sheeny A, Eilat-Tsanani S, Bishara E, Baron-Epel O (2013) Knowledge and health literacy are not associated with osteoporotic medication adherence, however income is, in Arab postmenopausal women. Patient Educ Couns 93(2):282–288. CrossRefPubMedGoogle Scholar
  126. 126.
    Hansen KE, Swenson ED, Baltz B, Schuna AA, Jones AN, Elliott ME (2008) Adherence to alendronate in male veterans. Osteoporos Int 19(3):349–356. CrossRefPubMedGoogle Scholar
  127. 127.
    Clark EM, Gould VC, Tobias JH, Horne R (2016) Natural history, reasons for, and impact of low/non-adherence to medications for osteoporosis in a cohort of community-dwelling older women already established on medication: a 2-year follow-up study. Osteoporos Int 27(2):579–590. CrossRefPubMedGoogle Scholar
  128. 128.
    Forbes CA, Deshpande S, Sorio-Vilela F, Kutikova L, Duffy S, Gouni-Berthold I, Hagstrom E (2018) A systematic literature review comparing methods for the measurement of patient persistence and adherence. Curr Med Res Opin:1–13. CrossRefGoogle Scholar
  129. 129.
    Gosch M, Jeske M, Kammerlander C, Roth T (2012) Osteoporosis and polypharmacy. Z Gerontol Geriatr 45(6):450–454. CrossRefPubMedGoogle Scholar
  130. 130.
    Reeve E, Wiese MD (2014) Benefits of deprescribing on patients’ adherence to medications. Int J Clin Pharm 36(1):26–29. CrossRefPubMedGoogle Scholar
  131. 131.
    Krass I, Schieback P, Dhippayom T (2015) Adherence to diabetes medication: a systematic review. Diabet Med 32(6):725–737. CrossRefPubMedGoogle Scholar
  132. 132.
    DiMatteo MR, Lepper HS, Croghan TW (2000) Depression is a risk factor for noncompliance with medical treatment: meta-analysis of the effects of anxiety and depression on patient adherence. Arch Intern Med 160(14):2101–2107CrossRefGoogle Scholar
  133. 133.
    Grenard JL, Munjas BA, Adams JL, Suttorp M, Maglione M, McGlynn EA, Gellad WF (2011) Depression and medication adherence in the treatment of chronic diseases in the United States: a meta-analysis. J Gen Intern Med 26(10):1175–1182. CrossRefPubMedPubMedCentralGoogle Scholar
  134. 134.
    Erez HB, Weller A, Vaisman N, Kreitler S (2012) The relationship of depression, anxiety and stress with low bone mineral density in post-menopausal women. Arch Osteoporos 7:247–255. CrossRefPubMedGoogle Scholar
  135. 135.
    Bianchi ML, Duca P, Vai S, Guglielmi G, Viti R, Battista C, Scillitani A, Muscarella S, Luisetto G, Camozzi V, Nuti R, Caffarelli C, Gonnelli S, Albanese C, De Tullio V, Isaia G, D'Amelio P, Broggi F, Croci M (2015) Improving adherence to and persistence with oral therapy of osteoporosis. Osteoporos Int 26(5):1629–1638. CrossRefPubMedGoogle Scholar
  136. 136.
    Hiligsmann M, Salas M, Hughes DA, Manias E, Gwadry-Sridhar FH, Linck P, Cowell W (2013) Interventions to improve osteoporosis medication adherence and persistence: a systematic review and literature appraisal by the ISPOR Medication Adherence & Persistence Special Interest Group. Osteoporos Int 24(12):2907–2918. CrossRefPubMedGoogle Scholar
  137. 137.
    Liu H, Michaud K, Nayak S, Karpf DB, Owens DK, Garber AM (2006) The cost-effectiveness of therapy with teriparatide and alendronate in women with severe osteoporosis. Arch Intern Med 166(11):1209–1217. CrossRefPubMedGoogle Scholar

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2018

Authors and Affiliations

  • C. T. Yeam
    • 1
  • S. Chia
    • 1
  • H. C. C. Tan
    • 1
  • Y. H. Kwan
    • 1
    • 2
  • W. Fong
    • 1
    • 3
    • 4
  • J. J. B. Seng
    • 1
    Email author
  1. 1.Duke-NUS Medical SchoolSingaporeSingapore
  2. 2.Program in Health Services and Systems ResearchDuke-NUS Medical SchoolSingaporeSingapore
  3. 3.Department of Rheumatology and ImmunologySingapore General HospitalSingaporeSingapore
  4. 4.Department of Medicine, Yong Loo Lin School of MedicineNational University of SingaporeSingaporeSingapore

Personalised recommendations