Determinants, consequences and potential solutions to poor adherence to anti-osteoporosis treatment: results of an expert group meeting organized by the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) and the International Osteoporosis Foundation (IOF)
Hiligsmann, M.; Cornelissen, D.; Vrijens, Bernardet al.
2019 • In Osteoporosis International, 30 (11), p. 2155-2165
Determinants, consequences and potential solutions to poor adherence to anti-osteoporosis treatment - results of an expert group meeting organized by the ESCEO and IOF.pdf
[en] Summary: Many patients at increased risk of fractures do not take their medication appropriately, resulting in a substantial decrease in the benefits of drug therapy. Improving medication adherence is urgently needed but remains laborious, given the numerous and multidimensional reasons for non-adherence, suggesting the need formeasurement-guided, multifactorial and individualized solutions.
Introduction: Poor adherence to medications is a major challenge in the treatment of osteoporosis. This paper aimed to provide an overview of the consequences, determinants and potential solutions to poor adherence and persistence to osteoporosis medication.
Methods: Aworking group was organized by the European Society on Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal diseases (ESCEO) to review consequences, determinants and potential solutions to adherence and to make recommendations for practice and further research. A systematic literature review and a face-to-face experts meeting were undertaken.
Results: Medication non-adherence is associated with increased risk of fractures, leading to a substantial decrease in the clinical and economic benefits of drug therapy. Reasons for non-adherence are numerous and multidimensional for each patient, depending on the interplay of multiple factors, suggesting the need for multifactorial and individualized solutions. Few interventions have been shown to improve adherence or persistence to osteoporosis treatment. Promising actions include patient education with counselling, adherence monitoring with feedback and dose simplification including flexible dosing regimen.
Recommendations for practice and further research were also provided. To adequately manage adherence, it is important to (1) understand the problem (initiation, implementation and/or persistence), (2) to measure adherence and (3) to identify the reason of non-adherence and fix it.
Conclusion: These recommendations are intended for clinicians to manage adherence of their patients and to researchers and policy makers to design, facilitate and appropriately use adherence interventions.
Disciplines :
General & internal medicine Public health, health care sciences & services
Author, co-author :
Hiligsmann, M.
Cornelissen, D.
Vrijens, Bernard ; Université de Liège - ULiège > Département des sciences de la santé publique > Département des sciences de la santé publique
Abrahamsen, B.
Al-Daghri, N.
Biver, E.
Brandi, M.L.
Bruyère, Olivier ; Université de Liège - ULiège > Département des sciences de la santé publique > Santé publique, Epidémiologie et Economie de la santé
Burlet, N.
Cooper, C.
Cortet, B.
Dennison, E.
Diez-Perez, A.
Gasparik, A.
Grosso, A.
Hadji, P.
Halbout, P.
Kanis, J.A.
Kaufman, J.M.
Laslop, A.
Maggi, S.
Rizzoli, R.
Thomas, T.
Tuzun, S.
Vlaskovska, M.
Reginster, Jean-Yves ; Université de Liège - ULiège > Département des sciences de la santé publique > Santé publique, Epidémiologie et Economie de la santé
Determinants, consequences and potential solutions to poor adherence to anti-osteoporosis treatment: results of an expert group meeting organized by the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) and the International Osteoporosis Foundation (IOF)
Kanis JA, Cooper C, Rizzoli R, Reginster JY, Scientific Advisory Board of the European Society for C, Economic Aspects of O et al (2019) European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Osteoporos Int 30(1):3–44
Hiligsmann M, McGowan B, Bennett K, Barry M, Reginster JY (2012) The clinical and economic burden of poor adherence and persistence with osteoporosis medications in Ireland. Value Health 15(5):604–612
Jha S, Wang Z, Laucis N, Bhattacharyya T (2015) Trends in media reports, oral bisphosphonate prescriptions, and hip fractures 1996-2012: an ecological analysis. J Bone Miner Res 30(12):2179–2187
Kanis JA, Cooper C, Rizzoli R, Abrahamsen B, Al-Daghri NM, Brandi ML et al (2017) Identification and management of patients at increased risk of osteoporotic fracture: outcomes of an ESCEO expert consensus meeting. Osteoporos Int 28(7):2023–2034
Sabate E (ed) (2003) Adherence to long-term therapies: evidence for action. World Health Organization, Geneva
Gold DT, Silverman S (2006) Review of adherence to medications for the treatment of osteoporosis. Curr Osteoporos Rep 4(1):21–27
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
Cornelissen D, et al. Interventions to improve osteoporosis medication adherence and persistence: an updated systematic review and literature appraisal In submission
Vrijens B, De Geest S, Hughes DA, Przemyslaw K, Demonceau J, Ruppar T et al (2012) A new taxonomy for describing and defining adherence to medications. Br J Clin Pharmacol 73(5):691–705
De Geest S, Zullig LL, Dunbar-Jacob J, Helmy R, Hughes DA, Wilson IB et al (2018) ESPACOMP Medication Adherence Reporting Guideline (EMERGE). Ann Intern Med 169(1):30–35
Lekkerkerker F, Kanis JA, Alsayed N, Bouvenot G, Burlet N, Cahall D, Chines A, Delmas P, Dreiser RL, Ethgen D, Hughes N, Kaufman JM, Korte S, Kreutz G, Laslop A, Mitlak B, Rabenda V, Rizzoli R, Santora A, Schimmer R, Tsouderos Y, Viethel P, Reginster JY, Group for the Respect of Ethics and Excellence in Science (GREES) (2007) Adherence to treatment of osteoporosis: a need for study. Osteoporos Int 18(10):1311–1317
Yeam CT, Chia S, Tan HCC, Kwan YH, Fong W, Seng JJB (2018) A systematic review of factors affecting medication adherence among patients with osteoporosis. Osteoporos Int 29(12):2623–2637
Fischer MA, Stedman MR, Lii J, Vogeli C, Shrank WH, Brookhart MA, Weissman JS (2010) Primary medication non-adherence: analysis of 195,930 electronic prescriptions. J Gen Intern Med 25(4):284–290
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
Rabenda V, Reginster JY (2010) Overcoming problems with adherence to osteoporosis medication. Expert Rev Pharmacoecon Outcomes Res 10(6):677–689
Rabenda V, Hiligsmann M, Reginster JY (2009) Poor adherence to oral bisphosphonate treatment and its consequences: a review of the evidence. Expert Opin Pharmacother 10(14):2303–2315
Strom O, Borgstrom F, Kanis JA, Compston J, Cooper C, McCloskey EV et al (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 6:59–155
Landfeldt E, Strom 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(2):433–443
Blaschke TF, Osterberg L, Vrijens B, Urquhart J (2012) Adherence to medications: insights arising from studies on the unreliable link between prescribed and actual drug dosing histories. Annu Rev Pharmacol Toxicol 52:275–301
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(6):811–818
van Boven JFM, 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
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. Osteoporos Int 20(2):299–307
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
Svedbom A, Hernlund E, Ivergard M, Compston J, Cooper C, Stenmark J et al (2013) Osteoporosis in the European Union: a compendium of country-specific reports. Arch Osteoporos 8:137
Kanis JA, Svedbom A, Harvey N, McCloskey EV (2014) The osteoporosis treatment gap. J Bone Miner Res 29(9):1926–1928
Blaschke TF, Osterberg L, Vrijens B, Urquhart J. Adherence to medications: insights arising from studies on the unreliable link between prescribed and actual drug dosing histories. Annu Rev Pharmacol. 2012;52:275−+
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 6:839–848
Wade SW, Satram-Hoang S, Nadkar A, Macarios D, Tosteson AN (2011) Impact of medication adherence on health care utilization and productivity: self-reported data from a cohort of postmenopausal women on osteoporosis therapy. Clin Ther 33(12):2006–2015
Siris ES, Selby PL, Saag KG, Borgstrom F, Herings RM, Silverman SL (2009) Impact of osteoporosis treatment adherence on fracture rates in North America and Europe. Am J Med 122(2 Suppl):S3–S13
Ross S, Samuels E, Gairy K, Iqbal S, Badamgarav E, Siris E (2011) A meta-analysis of osteoporotic fracture risk with medication nonadherence. Value Health 14(4):571–581
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
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
Hadji P, Papaioannou N, Gielen E, Feudjo Tepie M, Zhang E, Frieling I, Geusens P, Makras P, Resch H, Möller 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
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 Ph 21(9):824–U322
McClung MR, Wagman RB, Miller PD, Wang A, Lewiecki EM (2017) Observations following discontinuation of long-term denosumab therapy. Osteoporos Int 28(5):1723–1732
Lee YK, Nho JH, Ha YC, Koo KH (2012) Persistence with intravenous zoledronate in elderly patients with osteoporosis. Osteoporos Int 23(9):2329–2333
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
Kanis JA, Reginster JY, Kaufman JM, Ringe JD, Adachi JD, Hiligsmann M, Rizzoli R, Cooper C (2012) A reappraisal of generic bisphosphonates in osteoporosis. Osteoporos Int 23(1):213–221
Hiligsmann M, Rabenda V, Gathon HJ, Ethgen O, Reginster JY (2010) Potential clinical and economic impact of nonadherence with osteoporosis medications. Calcif Tissue Int 86(3):202–210
Hiligsmann M, Rabenda V, Bruyere O, Reginster JY (2010) The clinical and economic burden of non-adherence with oral bisphosphonates in osteoporotic patients. Health Policy 96(2):170–177
Danese MD, Badamgarav E, Bauer DC (2009) Effect of adherence on lifetime fractures in osteoporotic women treated with daily and weekly bisphosphonates. J Bone Miner Res 24(11):1819–1826
Strom O, Borgstrom F, Kanis J, Jonsson B (2009) Incorporating adherence into health economic modelling of osteoporosis. Osteoporos Int 20(1):23–34
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(2):159–166
Hiligsmann M, Reginster JY, Tosteson ANA, Bukata SV, Saag KG, Gold DT, Halbout P, Jiwa F, Lewiecki EM, Pinto D, Adachi JD, al-Daghri N, Bruyère O, Chandran M, Cooper C, Harvey NC, Einhorn TA, Kanis JA, Kendler DL, Messina OD, Rizzoli R, Si L, Silverman S (2019) Recommendations for the conduct of economic evaluations in osteoporosis: outcomes of an experts’ consensus meeting organized by the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) and the US branch of the International Osteoporosis Foundation. Osteoporos Int 30(1):45–57
Landfeldt E, Strom 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(2):433–443
Burkhart PV, Sabate E. Adherence to long-term therapies: evidence for action. J Nurs Scholarsh. 2003;35(3):207-
Kardas P, Lewek P, Matyjaszczyk M (2013) Determinants of patient adherence: a review of systematic reviews. Front Pharmacol 4
Johansson H, Siggeirsdottir K, Harvey NC, Oden A, Gudnason V, McCloskey E et al (2017) Imminent risk of fracture after fracture. Osteoporos Int 28(3):775–780
Beaton DE, Dyer S, Jiang D, Sujic R, Slater M, Sale JE et al (2014) Factors influencing the pharmacological management of osteoporosis after fragility fracture: results from the Ontario Osteoporosis Strategy’s fracture clinic screening program. Osteoporos Int 25(1):289–296
Majumdar SR, McAlister FA, Johnson JA, Weir DL, Bellerose D, Hanley DA et al (2014) Critical impact of patient knowledge and bone density testing on starting osteoporosis treatment after fragility fracture: secondary analyses from two controlled trials. Osteoporos Int 25(9):2173–2179
Morell S, Hemmeler C, Amsler F, Gross T (2017) Adherence to osteoporosis pharmacotherapy one year after osteoporotic fracture - a Swiss trauma center secondary prevention project. Swiss Med Wkly 147:w14451
Yu J, Brenneman SK, Sazonov V, Modi A (2015) Reasons for not initiating osteoporosis therapy among a managed care population. Patient Prefer Adherence 9:821–830
Tafaro L, Nati G, Leoni E, Baldini R, Cattaruzza MS, Mei M, Falaschi P (2013) Adherence to anti-osteoporotic therapies: role and determinants of “spot therapy”. Osteoporos Int 24(8):2319–2323
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. J Geriatr Phys Ther 34(2):72–81
Papaioannou A, Kennedy CC, Dolovich L, Lau E, Adachi JD (2007) Patient adherence to osteoporosis medications: problems, consequences and management strategies. Drugs Aging 24(1):37–55
Silverman SL, Schousboe JT, Gold DT (2011) Oral bisphosphonate compliance and persistence: a matter of choice? Osteoporos Int 22(1):21–26
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):394–402
Shu ADH, Stedman MR, Polinski JM, Jan SA, Patel M, Truppo C, Breiner L, Chen YY, Weiss TW, Solomon DH (2009) Adherence to osteoporosis medications after patient and physician brief education: post hoc analysis of a randomized controlled trial. Am J Manag Care 15(7):417–424
Solomon DH, Iversen MD, Avorn J, Gleeson T, Brookhart MA, Patrick AR, Rekedal L, Shrank WH, Lii J, Losina E, Katz JN (2012) Osteoporosis telephonic intervention to improve medication regimen adherence: a large, pragmatic, randomized controlled trial. Arch Intern Med 172(6):477–483
Delmas PD, Vrijens B, Eastell R, Roux C, Pols HA, Ringe JD et al (2007) Effect of monitoring bone turnover markers on persistence with risedronate treatment of postmenopausal osteoporosis. J Clin Endocrinol Metab 92(4):1296–1304
Vrijens B, Heidbuchel H (2015) Non-vitamin K antagonist oral anticoagulants: considerations on once- vs. twice-daily regimens and their potential impact on medication adherence. Europace 17(4):514–523
Vrijens B (2019) A Six Sigma framework to successfully manage medication adherence. Br J Clin Pharmacol 85:1661–1663
Rash JA, Campbell DJT, Tonelli M, Campbell TS (2016) A systematic review of interventions to improve adherence to statin medication: what do we know about what works? Prev Med 90:155–169
van Dalem J, Krass I, Aslani P (2012) Interventions promoting adherence to cardiovascular medicines. Int J Clin Pharm-Net 34(2):295–311
Chong WW, Aslani P, Chen TF (2011) Effectiveness of interventions to improve antidepressant medication adherence: a systematic review. Int J Clin Pract 65(9):954–975
Merle B, Chapurlat R, Vignot E, Thomas T, Haesebaert J, Schott AM (2017) Post-fracture care: do we need to educate patients rather than doctors? The PREVOST randomized controlled trial. Osteoporos Int 28(5):1549–1558
Seuffert P, Sagebien CA, McDonnell M, O’Hara DA. Evaluation of osteoporosis risk and initiation of a nurse practitioner intervention program in an orthopedic practice. Arch Osteoporos. 2016;11(1)
Beaton DE, Mamdani M, Zheng H, Jaglal S, Cadarette SM, Bogoch ER, et al. Improvements in osteoporosis testing and care are found following the wide scale implementation of the Ontario Fracture Clinic Screening Program: an interrupted time series analysis. Medicine. 2017;96(48)
Parsons C, Harvey N, Shepstone L, Kanis J, Lenaghan E, Clarke S, et al. Systematic screening using Frax leads to increased use of, and adherence to, anti-osteoporosis medications: the Uk Scoop Trial. Osteoporosis Int. 2018;29:613-
Nielsen D, Ryg J, Nielsen W, Knold B, Nissen N, Brixen K (2010) Patient education in groups increases knowledge of osteoporosis and adherence to treatment: a two-year randomized controlled trial. Patient Educ Couns 81(2):155–160
Stuurman-Bieze AGG, Hiddink EG, van Boven JFM, Vegter S (2014) Proactive pharmaceutical care interventions decrease patients’ nonadherence to osteoporosis medication. Osteoporos Int 25(6):1807–1812
Ducoulombier V, Luraschi H, Forzy G, Vandecandelaere M, Houvenagel E (2015) Contribution of phone follow-up to improved adherence to oral osteoporosis treatment. Am J Pharm Benefist 7(3):E81–EE9
Hiligsmann M, Reginster JY (2019) Cost-effectiveness of gastro-resistant risedronate tablets for the treatment of postmenopausal women with osteoporosis in France. Osteoporos Int 30(3):649–658
Oral A, Lorenc R, Investigators F-AS (2015) Compliance, persistence, and preference outcomes of postmenopausal osteoporotic women receiving a flexible or fixed regimen of daily risedronate: a multicenter, prospective, parallel group study. Acta Orthop Traumatol Turc 49(1):67–74
Barry MJ, Edgman-Levitan S (2012) Shared decision making--pinnacle of patient-centered care. N Engl J Med 366(9):780–781
Stacey D, Legare F, Lewis K, Barry MJ, Bennett CL, Eden KB et al (2017) Decision aids for people facing health treatment or screening decisions. Cochrane Db Syst Rev 4
Montori VM, Shah ND, Pencille LJ, Branda ME, Van Houten HK, Swiglo BA et al (2011) Use of a decision aid to improve treatment decisions in osteoporosis: the osteoporosis choice randomized trial. Am J Med 124(6):549–556
Hiligsmann M, Ronda G, van der Weijden T, Boonen A (2016) The development of a personalized patient education tool for decision making for postmenopausal women with osteoporosis. Osteoporos Int 27(8):2489–2496
Smallwood AJ, Schapira MM, Fedders M, Neuner JM (2017) A pilot randomized controlled trial of a decision aid with tailored fracture risk tool delivered via a patient portal. Osteoporos Int 28(2):567–576
Lewiecki EM (2010) Risk communication and shared decision making in the care of patients with osteoporosis. J Clin Densitom 13(4):335–345
Gasparik AI (2014) Clinical setting influences patterns of interaction between osteoporosis patient and physician. Calcif Tissue Int 95(2):122–124
Hiligsmann M, Pinto D, Dennison E, Al-Daghri N, Beaudart C, Branco J et al (2019) Patients’ preferences for osteoarthritis treatment: the value of stated-preference studies. Aging Clin Exp Res 31(1):1–3
de Wit M, Cooper C, Tugwell P, Bere N, Kirwan J, Conaghan PG et al (2019) Practical guidance for engaging patients in health research, treatment guidelines and regulatory processes: results of an expert group meeting organized by the World Health Organization (WHO) and the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO). Aging Clin Exp Res 31(7):905–915
Silverman S, Gold DT (2018) Medication decision-making in osteoporosis: can we explain why patients do not take their osteoporosis medications? Current Osteoporosis Reports 16(6):772–774
