[en] Poor therapeutic adherence is a major issue faced by physicians today. This paper summarizes the adherence rates with oral bisphosphonate (OBP) treatment in clinical practice and their impact on clinical outcomes. Studies systematically demonstrated that overall compliance and persistence with OBPs among osteoporotic women are poor. Although extending dosing intervals improved adherence, the gains are suboptimal. Most importantly, low compliance and persistence rates consistently resulted in increased rates of fractures. The results emphasize the importance of adherence to treatment to achieve optimal antifracture efficacy. There is an urgent need to implement strategies and to encourage physicians to take measures that increase patients' awareness of the need to use osteoporosis medications as directed in order to benefit from them fully.
Disciplines :
General & internal medicine
Author, co-author :
Rabenda, Véronique ; Université de Liège - ULiège > Département des sciences de la santé publique > Epidémiologie et santé publique
Hiligsmann, Mickaël ; Université de Liège - ULiège > HEC-Ecole de gestion : UER > Economie industrielle
Reginster, Jean-Yves ; Université de Liège - ULiège > Département des sciences de la santé publique > Epidémiologie et santé publique
Language :
English
Title :
Poor adherence to oral bisphosphonate treatment and its consequences: a review of the evidence.
Johnell O, Kanis J. Epidemiology of osteoporotic fractures. Osteoporos Int 2005;16(Suppl 2):S3-7
Johnell O, Kanis JA. An estimate of the worldwide prevalence and disability associated with osteoporotic fractures. Osteoporos Int 2006;17:1726-1733 (Pubitemid 44607392)
Ray NF, Chan JK, Thamer M, Melton LJ. Medical expenditures for the treatment of osteoporotic fractures in the United States in 1995: report from the National Osteoporosis Foundation. J Bone Miner Res 1997;12:24-35
Ross PD. Osteoporosis. Frequency, consequences, and risk factors. Arch Intern Med 1996;156:1399-1411
Chrischilles EA, Butler CD, Davis CS, Wallace RB. A model of lifetime osteoporosis impact. Arch Intern Med 1991;151:2026-2032
Schwenkglenks M, Lippuner K, Hauselmann HJ, Szucs TD. A model of osteoporosis impact in Switzerland 2000-2020. Osteoporos Int 2005;16:659-671
Black DM, Cummings SR, Karpf DB, et al. Randomized trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Fracture Intervention Trial Research Group. Lancet 1996;348:1535-1541
Harris ST, Watts NB, Genant HK, et al. Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis: a randomized controlled trial. Vertebral Efficacy with Risedronate Therapy (VERT) Study Group. JAMA 1999;282:1344-1352
Reginster JY, Minne HW, Sorensen OH, et al. Randomized trial of the effects of risedronate on vertebral fractures in women with established postmenopausal osteoporosis. Vertebral Efficacy with Risedronate Therapy (VERT) Study Group. Osteoporos Int 2000;11:83-91
McClung MR, Geusens P, Miller PD, et al. Effects of risedronate on the risk of hip fracture in elderly women. Hip Intervention Program Study Group. N Engl J Med 2001;344:333-340
Chesnut III CH, Skag A, Christiansen C, et al. Oral Ibandronate Osteoporosis Vertebral Fracture Trial in North America and Europe (BONE). Effects of oral ibandronate administered daily or intermittently on fracture risk in postmenopausal osteoporosis. Bone Miner Res 2004;19:1241-1249
Andrade SE, Majumdar SR, Chan KA, et al. Low frequency of treatment of osteoporosis among postmenopausal women following a fracture. Arch Intern Med 2003;163:2052-2057 (Pubitemid 37151247)
Gardner MJ, Flik KR, Mooar P, Lane JM. Improvement in the undertreatment of osteoporosis following hip fracture. J Bone Joint Surg Am 2002;84-A(8):1342-1348 (Pubitemid 35407578)
Panneman MJ, Lips P, Sen SS, Herings RM. Undertreatment with anti-osteoporotic drugs after hospitalization for fracture. Osteoporos Int 2004;15:120-124 (Pubitemid 38252425)
Freedman KB, Kaplan FS, Bilker WB, et al. Treatment of osteoporosis: are physicians missing an opportunity? J Bone Joint Surg Am 2000;82-A(8):1063-1070
Rabenda V, Vanoverloop J, Fabri V, et al. Low incidence of anti-osteoporosis treatment after hip fracture. J Bone Joint Surg Am 2008;90:2142-2148 • This paper showed that the vast majority of patients did not receive any osteoporosis medications after a hip fracture and that among patients who initiated treatment after a hip fracture, the adherence was suboptimal.
Ettinger M, Gallagher R, Amonkar M, et al. Medication persistence is improved with less frequent dosing of bisphosphonates, but remains inadequate. Arthritis Rheum 2004;50(Suppl 1):S513-4
Recker RR, Gallagher R, Maccosbe PE. Effect of dosing frequency on bisphosphonate medication adherence in a large longitudinal cohort of women. Mayo Clin Proc 2005;80:856-861 (Pubitemid 40911458)
Cramer JA, Amonkar MM, Hebborn A, et al. Compliance and persistence with bisphosphonate dosing regimens among women with postmenopausal osteoporosis. Curr Med Res Opin 2005;21:1453-1460 (Pubitemid 41368578)
Lo JC, Pressman AR, Omar MA, Ettinger B. Persistence with weekly alendronate therapy among postmenopausal women. Osteoporos Int 2006;17:922-928 (Pubitemid 43781507)
Weycker D, Macarios D, Edelsberg J, Oster G. Compliance with osteoporosis drug therapy and risk of fracture. Osteoporos Int 2007;18:271-277 (Pubitemid 46233172)
Siris ES, Harris ST, Rosen CJ, et al. Adherence to bisphosphonate therapy and fracture rates in osteoporotic women: relationship to vertebral and nonvertebral fractures from 2 US claims databases. Mayo Clin Proc 2006;81:1013-1022 • This paper showed the probability of fracture along a gradient of adherence. At an MPR < 50%, the probability of fracture remained consistent at about 11%. The probability of fracture declines with a shallow slope for MPR values from 50% to 75% and then more sharply from 75% to 100%.
van den Boogaard CH, Breekveldt-Postma NS, Borggreve SE, et al. Persistent bisphosphonate use and the risk of osteoporotic fractures in clinical practice: a database analysis study. Curr Med Res Opin 2006;22:1757-1764
Penning-van Beest FJ, Erkens JA, Olson M, Herings RM. Loss of treatment benefit due to low compliance with bisphosphonate therapy. Osteoporos Int 2008;19:511-517
Rabenda V, Mertens R, Fabri V, et al. Adherence to bisphosphonates therapy and hip fracture risk in osteoporotic women. Osteoporos Int 2008;19:811-818
Yood RA, Emani S, Reed JI, et al. Compliance with pharmacologic therapy for osteoporosis. Osteoporos Int 2003;14:965-968
Sebaldt RJ, Shane LG, Pham B, et al. Impact of non-compliance and non-persistence with daily bisphosphonates on longer-term effectiveness outcomes in patients with osteoporosis treated in tertiary specialist care. J Bone Miner Res 2004;19(Suppl 1):S445
Eastell R, Garnero P, Vrijens B, et al. Influence of patient compliance with risedronate therapy on bone turnover marker and bone mineral density response:the IMPACT study. Calcif Tissue Int 2003;72:408
Briesacher BA, Andrade SE, Yood RA, Kahler KH. Consequences of poor compliance with bisphosphonates. Bone 2007;41:882-887
Bronder E, Klimpel A. Unused drugs returned to the pharmacy-new data. Int J Clin Pharmacol Ther 2001;39:480-483 (Pubitemid 33040590)
Col N, Fanale JE, Kronholm P. The role of medication noncompliance and adverse drug reactions in hospitalizations of the elderly. Arch Intern Med 1990;150:841-845 (Pubitemid 20122061)
Berg JS, Dischler J, Wagner DJ, et al. Medication compliance: a healthcare problem. Ann Pharmacother 1993;27(9 Suppl):S1-24
McCombs JS, Thibaud P, McLaughlin-Miley C, et al. Compliance with drug therapies for the treatment and prevention of osteoporosis. Maturitas 2004;48:271-287 (Pubitemid 38781153)
Huybrechts KF, Ishak KJ, Caro JJ. Assessment of compliance with osteoporosis treatment and its consequences in a managed care population. Bone 2006;38:922-928
Burrell A, Wong P, Ollendorf D, et al. Defining compliance, adherence and persistence: ISPOR Special Interest Working Group. Value Health 2005;8:A194-5
Tosteson ANA, Grove MR, Hammond CS, et al. Early discontinuation of treatment for osteoporosis. Am J Med 2003;115:209-216
Turbi C, Herrero-Beaumont G, Acebes JC, et al. 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 2004;26:245-256 (Pubitemid 38339016)
Rossini M, Bianchi G, Di Munno O, et al. Determinants of adherence to osteoporosis treatment in clinical practice. Osteoporos Int 2006;17:914-921 (Pubitemid 43781506)
Segal E, Tamir A, Ish-Shalom S. Compliance of osteoporotic patients with different treatment regimens. Isr Med Assoc J 2003;5:859-862 (Pubitemid 38008106)
Papaioannou A, Ioannidis G, Adachi JD, et al. Adherence to bisphosphonates and hormone replacement therapy in a tertiary care setting of patients in the CANDOO database. Osteoporos Int 2003;14:808-813 (Pubitemid 37462130)
Solomon DH, Avorn J, Katz JN, et al. Compliance with osteoporosis medications. Arch Intern Med 2005;165:2414-2419
Brookhart MA, Avorn J, Katz JN, et al. Gaps in treatment among users of osteoporosis medications: the dynamics of noncompliance. Am J Med 2007;120:251-256 (Pubitemid 46341156)
Brankin E, Walker M, Lynch N, et al. 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 2006;22:1249-1256 (Pubitemid 44085576)
Bart R, Goette S, Hadji P, Hammerschmidt T. Persistence and compliance with daily and weekly-administered bisphosphonates for osteoporosis treatment in Germany. Osteoporos Int 2005;16(Suppl 3):S45
Boccuzzi SJ, Foltz SH, Omar MA, Kahler KH. Assessment of adherence and persistence with daily and weekly dosing regimens of oral bisphosphonates. Osteoporos Int 2005;16(Suppl 3):S3
Silverman SL, Cramer JA, Sunyecz JA, et al. Women are more persistent with monthly bisphosphonate therapy compared to weekly bisphosphonates: 12 months results from two retrospective databases [abstract W366]. J Bone Miner Res 2007;22(Suppl 1):454 • Adherence is improved with monthly regimen.
Cooper A, Drake J, Brankin E, et al. Treatment persistence with once-monthly ibandronate and patient support vs. once-weekly alendronate: results from the PERSIST study. Int J Clin Pract 2006;60:896-905 (Pubitemid 44082279)
Boccuzzi SJ, Foltz SH, Omar MA, et al. Adherence and persistence associated with pharmacology treatment of osteoporosis. Osteoporos Int 2005;16(Suppl 3):S24
Hamilton B, McKoy K, Taggart H. Tolerability and compliance with risedronate in clinical practice. Osteoporos Int 2003;1:259-262 (Pubitemid 40826240)
Ettinger B, Pressman AR, Schein J, et al. Alendronate use among 812 women: prevalence of gastrointestinal complaints, non-compliance with patient's instructions and discontinuation. J Manag Care Pharm 1998;4:488-492
Aki S, Eskiyurt N, Akarirmak U, et al. Gastrointestinal side effect profile due to the use of alendronate in the treatment of osteoporosis. Yonsei Med J 2003;44:961-967 (Pubitemid 38081560)
Gold DT, Martin BC, Frytak JR, et al. A claims database analysis of persistence with alendronate therapy and fracture risk in post-menopausal women with osteoporosis. Curr Med Res Opin 2007;23:585-594
Goettsch WG, Penning F, Erkens JE, et al. Persistent bisphosphonate usage reduces the risk of hospitalizations for osteoporotic fractures. J Bone Miner Res 2005;20(Suppl 1):S278
Caro JJ, Ishak KJ, Huybrechts KF, et al. The impact of compliance with osteoporosis therapy on fracture rates in actual practice. Osteoporos Int 2004;15:1003-1008
Curtis JR, Westfall AO, Cheng H, et al. The benefit of adherence with bisphosphonates depends on age and fracture type: results form an analysis of 101,038 new bisphosphonate users. J Bone Miner Res 2008;23:1435-1441
Jaglal S, Thiruchelvam D, Hawker G. Impact of adherence to osteoporosis medications on fracture rates: a population-based study. Presented at the American Society for Bone and Mineral Research 29th Annual Meeting; September, 2007; Honolulu, Hawaii, USA. Abstract 1275
Gothe H, Hadji P, Hoeer A, et al. Good persistence and adherence with oral bisphosphonates reduce fracture rate in patients with osteoporotic fractures. Calcif Tissue Int 2007;80(Suppl 1):S129
Cotte FE, Mercier F, De Pouvourville G. Relationship between compliance and persistence with osteoporosis medications and fracture risk in primary health care in France: a retrospective case-control analysis. Clin Ther 2008;30:2410-2422
Hoër A, Seidlitz C, Gothe H, et al. Influence on persistence and adherence with oral bisphosphonates on fracture rates in osteoporosis. Patient Preference and Adherence 2009;3:25-30
Lekkerkerker F, Kanis JA, Alsayed N, et al. Group for the Respect of Ethics and Excellence in Science (GREES). Adherence to treatment of osteoporosis: a need for study. Osteoporos Int 2007;18:1311-1317
Reginster JY, Adami S, Lakatos P, et al. Efficacy and tolerability of once-monthly oral ibandronate in postmenopausal osteoporosis: 2 year results from the MOBILE study. Ann Rheum Dis 2006;65:654-661
Eisman JA, Civitelli R, Adami S, et al. Efficacy and tolerability of intravenous ibandronate injections in postmenopausal osteoporosis: 2-year results from the DIVA study. J Rheumatol 2008;35:488-497
Black DM, Delmas PD, Eastell R, et al. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med 2007;356:1809-1822 (Pubitemid 46698462)
Harris ST, Blumentals WA, Miller PD. Ibandronate and the risk of non-vertebral and clinical fractures in women with postmenopausal osteoporosis: results of a meta-analysis of phase III studies. Curr Med Res Opin 2008;24:237-245 A meta-analysis of the anti-fracture efficacy of Ibandronate.
Emkey R, Koltun W, Beusterien K, et al. Patient preference for once-monthly ibandronate versus once-weekly alendronate in a randomized, open-label, cross-over trial: the Boniva Alendronate Trial in Osteoporosis (BALTO). Curr Med Res Opin 2005;21:1895-1903 (Pubitemid 41803098)
Hadji P, Benhamou CL, Devas V, et al. Women with postmenopausal osteoporosis prefer once-monthly oral ibandronate to weekly oral alendronate: results of BALTO II. Osteoporos Int 2006;17(Suppl 1):S69
Lewiecki EM, Babbitt AM, Piziak VK, et al. Adherence to and gastrointestinal tolerability of monthly oral and quarterly intravenous ibandronate in women with previous intolerance in oral bisphosphonates: a 12-month, open-label prospective evaluation. Clin Ther 2008;30:605-621
McClung M, Recker R, Miller P, et al. Intravenous zoledronic acid 5 mg in the treatment of postmenopausal women with low bone density previously treated with alendronate. Bone 2007;41:122-128 (Pubitemid 46901056)
Saag K, Lindsay R, Kriegman A, et al. A single zoledronic acid infusion reduces bone resorption markers more rapidly than weekly oral alendronate in postmenopausal women with low bone mineral density. Bone 2007;40:1238-1243 (Pubitemid 46550991)
Hiligsmann M, Rabenda V, Gathon HJ, et al. Clinical and economic implications of non-adherence with osteoporosis medications. Osteoporos Int 2009;20:S1,5
Sheehy O, Kindundu C, Barbeau M, Lelorier J. Adherence to weekly oral bisphosphonate therapy: cost of wasted drugs and fractures. Osteoporos Int 2009: published online 20 January 2009; doi:10.1007/s00198-008-0829-2
Simpson SH, Eurich DT, Majumdar SR, et al. A meta-analysis of the association between adherence to drug therapy and mortality. BMJ 2006;333:15
Clowes JA, Peel NF, Eastell R. The impact of monitoring on adherence and persistence with antiresorptive treatment for postmenopausal osteoporosis: a randomized controlled trial. J Clin Endocrinol Metab 2004;89:1117-1123 (Pubitemid 38368399)
Delmas PD, Vrijns B, Roux C, et al. Reinforcement message based on bone turnover marker response influences long-term persistence with risedronate in osteoporosis: the IMPACT study. J Bone Miner Res 2003;18(Suppl 2):S374
Haynes RB, Yao X, Degani A, et al. Interventions to enhance medication adherence. Cochrane Database Syst Rev 2005;4:CD000011 • A review of strategies which may improve medication adherence.
Seely EW, Ravnikar A, McClung BL. Patient-provider decisions about long-term therapy. Am J Manag Care 1998;4(2 Suppl):S70-S77
Bond WS, Hussar DA. Detection methods and strategies for improving medication compliance. Am J Hosp Pharm 1991;48:1978-1988
Simon JA, Lewiecki EM, Smith ME, et al. Patient preference for once weekly alendronate 70 mg versus once daily 10 mg: a multicentre randomized open label crossover study. Clin Ther 2002;24:1871-1886
Simon JA, Beusterien K, Leidy NK, et al. Women with postmenopausal osteoporosis express a preference for once-monthly versus once-weekly bisphosphonate treatment. Female Patient 2005;30:31-36
