Osteoporosis International

, Volume 18, Issue 10, pp 1311–1317

Adherence to treatment of osteoporosis: a need for study

  • F. Lekkerkerker
  • J. A. Kanis
  • N. Alsayed
  • G. Bouvenot
  • N. Burlet
  • D. Cahall
  • A. Chines
  • P. Delmas
  • R.-L. Dreiser
  • D. Ethgen
  • N. Hughes
  • J.-M. Kaufman
  • S. Korte
  • G. Kreutz
  • A. Laslop
  • B. Mitlak
  • V. Rabenda
  • R. Rizzoli
  • A. Santora
  • R. Schimmer
  • Y. Tsouderos
  • P. Viethel
  • J.-Y. Reginster



Adherence to anti-osteoporosis medications is currently low and is associated with poor anti-fracture efficacy. This manuscript reviews the potential design of clinical studies that aim to demonstrate improved adherence, with new chemical entities to be used in the management of osteoporosis.


Several medications have been unequivocally shown to decrease fracture rates in clinical trials. However, in real life settings, long-term persistence and compliance to anti-osteoporosis medication is poor, hence decreasing the clinical benefits for patients.


An extensive search of Medline from 1985 to 2006 retrieved all trials including the keywords osteoporosis, compliance, persistence or adherence followed by a critical appraisal of the data obtained through a consensus expert meeting.


The impact of non-adherence on the clinical development of interventions is reviewed, so that clinicians, regulatory agencies and reimbursement agencies might be better informed of the problem, in order to stimulate the necessary research to document adherence.


Adherence to therapy is a major problem in the treatment of osteoporosis. Both patients and medication factors are involved. Adherence studies are an important aspect of outcomes studies, but study methodologies are not well developed at the moment and should be improved. Performing adherence studies will be stimulated when registration authorities accept the result of these studies and include the relevant information in Sect. 5.1 of the summary of product characteristics. Reimbursement authorities might also consider such studies as important information for decisions on reimbursement.


Adherence Compliance Persistence Registration Reimbursement 


  1. 1.
    Caro JJ, Ishak KJ, Huybrechts KF et al (2004) The impact of compliance with osteoporosis therapy on fracture rates in actual practice. Osteoporosis Int 15:1003–1008CrossRefGoogle Scholar
  2. 2.
    Huybrechts KF, Ishak KJ, Caro JJ (2006) Assessment of compliance with osteoporosis treatment and its consequences in a managed care population. Bone 38:922–928PubMedCrossRefGoogle Scholar
  3. 3.
    Siris ES, Harris ST, Rosen CJ et al (2006) Adherence to bisphosphonate therapy and fracture rtes in osteoporotic women: relationship to vertebral and non-vertebral fractures from 2 US claims databases. Mayo Clinic Proc 81:1013–1022CrossRefGoogle Scholar
  4. 4.
    Clowes JA, Peel NFA, Eastell R (2004) The impact of monitoring on adherence and persistence with antiresorptive treatment for postmenopausal osteoporosis: a randomised controlled trial. J Clin Endocrinol Metab 89:1117–1123PubMedCrossRefGoogle Scholar
  5. 5.
    Yood RA, Emani S, Reid JI et al (2003) Compliance with pharmacological therapy for osteoporosis. Osteoporosis Int 14:965–968CrossRefGoogle Scholar
  6. 6.
    Silverman S, Siris E, Abbott T et al (2003) Adherence to bisphosphonate therapy is associated with decreased non-vertebral osteoporotic fracture risk. J Bone Miner Res 20 (suppl 1):S286Google Scholar
  7. 7.
    Weycker D, Macarios D, Edelsberg J et al (2006) Compliance with drug therapy for postmenopausal osteoporosis. Osteoporosis Int 17:1645–1652CrossRefGoogle Scholar
  8. 8.
    Compston JE, Seeman E (2006) Compliance with osteoporosis therapy is the weakest link. Lancet 368:2005–2006CrossRefGoogle Scholar
  9. 9.
    Miller NH (1997) Compliance with treatment regimens in chronic asymptomatic diseases. Am J Med 102:43–49PubMedCrossRefGoogle Scholar
  10. 10.
    Willey C, Redding C, Stafford J et al (2000) Stages of change for adherence with medication regimens for chronic diseases: development and validation of a measure. Clin Ther 22:858–871PubMedCrossRefGoogle Scholar
  11. 11.
    Donovan JL (1995) Patient decision making. The missing ingredient in compliance research. Int J Technol Assess Health Care 11:443–455PubMedGoogle Scholar
  12. 12.
    Kyngas H, Duffy ME, Kroll T (2000) Conceptual analysis of compliance. J Clin Nurs 9:5–12PubMedCrossRefGoogle Scholar
  13. 13.
    Lutfey KE, Wishner WJ (1999) Beyond “compliance” is “adherence”. Improving the prospect of diabetes care. Diabetes Care 22:635–639PubMedCrossRefGoogle Scholar
  14. 14.
    Henneman EA, Lee JL, Cohen JI (1995) Collaboration: a concept analysis. J Adv Nurs 21:103–109PubMedCrossRefGoogle Scholar
  15. 15.
    Madden BP (1990) The hybrid model for concept development: its value for the study of therapeutic alliance. ANS Adv Nurs Sci 12:75–87PubMedGoogle Scholar
  16. 16.
    Mullen PD (1997) Compliance becomes concordance. B Med J 314:691–692Google Scholar
  17. 17.
    McCombs JS, Thiebaudet P, McLaughlin-Milet C et al (2004) Compliance with drug therapies for the treatment and prevention of osteoporosis. Maturitas 48:271–287PubMedCrossRefGoogle Scholar
  18. 18.
    Cooper A, Drake J, Brankin E, on behalf of the persist investigators (2006) Treatment persistence with once-monthly ibandronate and patient support vs. once weekly alendronate: results from the PERSIST study. J Clin Practice 60:896–905CrossRefGoogle Scholar
  19. 19.
    Cramer JA, Amonkar MM, Hebborn A et al (2005) Compliance and persistence with bisphosphonate dosing regimens among women with postmenopausal osteoporosis. Curr Med Res Opin 21:1453–1460PubMedCrossRefGoogle Scholar
  20. 20.
    Fardellone P, Gaudin AF, Cotte FE (2005) Comparison of the persistence of daily and weekly bisphosphonates in female patients treated for osteoporosis. J Bone Miner Res 20 (Suppl 1):S285–S286Google Scholar
  21. 21.
    Solomon DH, Avorn J, Katz et al (2005) Compliance with osteoporosis indications. Arch Intern Med 165:2414–2419PubMedCrossRefGoogle Scholar
  22. 22.
    Docherty SM, Goodley A, Steel SA (2005) Compliance and effect of bone protective treatment in elderly females: 5 year follow-up study. Rheumatology 44(Suppl 1):134Google Scholar
  23. 23.
    Tosteson ANA, Grove MR, Hammond CS et al (2003) Early discontinuation of treatment for osteoporosis. Am J Med 115:209–216PubMedCrossRefGoogle Scholar
  24. 24.
    Hamilton B, McCoy K, Taggart H (2003) Tolerability and compliance with risedronate in clinical practice. Osteoporosis Int 14:259–262Google Scholar
  25. 25.
    Prowse D, McGetrick V, Thompson AJ et al (2005) Persistence with oral therapy is high amongst patients followed in a DGH osteoporosis. Clinical Rheumatology 44(Suppl):135CrossRefGoogle Scholar
  26. 26.
    Briesacher BA, Andrade S, Kahler K et al (2006) Economic impact of the previous year’s adherence with bisphosphonates. J Bone Miner Res 21(suppl 1):S171Google Scholar
  27. 27.
    World Health Organization (2003) Adherence to long-term therapies: Evidence for action. WHO, Geneva, SwitzerlandGoogle Scholar
  28. 28.
    Lamberg L (2000) Patient-physician relationship critical even during brief “medication checks”. JAMA 284:29–31PubMedCrossRefGoogle Scholar
  29. 29.
    Eraker SA, Kirscht JP, Becker MH (1984) Understanding and improving patient compliance. Ann Intern Med 100:258–268PubMedGoogle Scholar
  30. 30.
    Ammassari A, Trotta MP, Murri R et al (2002) Study group correlates and predictors of adherence to highly active antiretroviral therapy: Overview of Published. JAIDS 31(suppl 3):S123–S127PubMedGoogle Scholar
  31. 31.
    McCloskey E, de Takats D, Orgee J et al (2005) Characteristics associated with non-persistence during daily therapy. Experience from the placebo wing of a community-based clinical trial. J Bone Miner Res 20(suppl 1):S282Google Scholar
  32. 32.
    Claxton AJ, Cranmer J, Pierce C (2001) A systematic review of the associations between dose regimens and medication compliance. Clin Ther 23:1296–1310PubMedCrossRefGoogle Scholar
  33. 33.
    Thompson P, Cooper C, Carr A (2005) Factors influencing adherence to bisphosphonates for osteoporosis. J Bone Miner Res 20 (suppl):S394Google Scholar
  34. 34.
    Irvine J, Baker B, Smith J et al (1999) Poor adherence to placebo or amiodarone therapy predicts mortality: results from the CAMIAT study Psychosom Med 61:566–575PubMedGoogle Scholar
  35. 35.
    Granger BB, Swedberg K, Ekman I, for the CHARM investigators (2005) Adherence to candesartan and placebo and outcomes in chronic heart failure in the CHARM programme: double-blind, randomised, controlled clinical trial. Lancet 366:2005–2011PubMedCrossRefGoogle Scholar
  36. 36.
    Delmas PD, Vrijens B, Eastell R et al (2007) Improving measurements of persistence on actonel treatment (IMPACT) investigators. Effect of monitoring bone turnover markers on persistence with risedronate treatment of postmenopausal osteoporosis. J Clin Endocrinol Metab 92:296–304CrossRefGoogle Scholar
  37. 37.
    Cramer JA, Silverman S (2006) Persistence with Bisphosphonate Treatment for Osteoporosis: Finding the root of the problem. Am J Med 119:S12–S17PubMedCrossRefGoogle Scholar
  38. 38.
    Kanis JA et al (2007) Glucocorticoid-induced osteoporosis: a systematic review and cost-utility analysis. Health Technol Assess 11:1–256Google Scholar
  39. 39.
    Stevenson M, Davies S (2006) DSU economic evaluation of pooled alendronate and risedronate compared with strontium ranelate, raloxifene, etidronate and teriparatide http://guidance.nice.org.uk/page.aspx?o=370643)
  40. 40.
    Spilker B (1991) Methods of assessing and improving patient compliance in clinical trials. In: Cramer JA, Spilker B (eds) (1991) Patient compliance in medical practice and clinical trials. Raven press, New York pp 37–56Google Scholar
  41. 41.
    Melnikow J, Kiefe C (1994) Patient compliance and medical research. Issues in methodology. J Gen Int Med 9:96–105CrossRefGoogle Scholar
  42. 42.
    Turbi C, Herrero-Beaumont G, Acebes JC et al (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 26:245–256PubMedCrossRefGoogle Scholar
  43. 43.
    Farmer KC (1999) Methods for measuring and monitoring medication regimen adherence in clinical trials and clinical practice. Clin Ther 21:1074–1090PubMedCrossRefGoogle Scholar
  44. 44.
    Straka RJ, Fish JT, Benson SR et al (1997) Patient self-reporting of compliance does not correspond with electronic monitoring: an evaluation using isosorbide dinitrate as a model drug. Pharmacotherapy 17:126–132PubMedGoogle Scholar
  45. 45.
    Lee JY, Kusek JW, Greene PG et al (1996) Assessing medication adherence by pill count and electronic monitoring in the African American Study of Kidney Disease and Hypertension (AASK) Pilot Study. Am J Hypertens 9:719–725PubMedCrossRefGoogle Scholar
  46. 46.
    Mason BJ, Matsuyama JR, Jue SG (1995) Assessment of sulfonylurea adherence and metabolic control. Diabetes Educ 21:52–57PubMedCrossRefGoogle Scholar
  47. 47.
    Paes AH, Bakker A, Soe-Agnie CJ (1998) Measurement of patient compliance. Pharm World Sci 20:73–77PubMedCrossRefGoogle Scholar
  48. 48.
    Pullar T, Feely M (1990) Problems of compliance with drug treatment: new solutions? Pharm J 245:213–215Google Scholar
  49. 49.
    Schwed A, Fallab CL, Burnier M et al (1999) Electronic monitoring of compliance to lipid-lowering therapy in clinical practice. J Clin Pharmacol 39:402–409PubMedCrossRefGoogle Scholar

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2007

Authors and Affiliations

  • F. Lekkerkerker
    • 1
  • J. A. Kanis
    • 2
  • N. Alsayed
    • 3
  • G. Bouvenot
    • 4
  • N. Burlet
    • 5
  • D. Cahall
    • 6
  • A. Chines
    • 7
  • P. Delmas
    • 8
  • R.-L. Dreiser
    • 9
  • D. Ethgen
    • 10
  • N. Hughes
    • 11
  • J.-M. Kaufman
    • 12
  • S. Korte
    • 13
  • G. Kreutz
    • 14
  • A. Laslop
    • 15
  • B. Mitlak
    • 16
  • V. Rabenda
    • 17
  • R. Rizzoli
    • 18
  • A. Santora
    • 19
  • R. Schimmer
    • 20
  • Y. Tsouderos
    • 21
  • P. Viethel
    • 22
  • J.-Y. Reginster
    • 23
    • 24
  1. 1.Medicines Evaluation BoardThe HagueThe Netherlands
  2. 2.University Of SheffieldSheffieldUK
  3. 3.Supreme S.ALiègeBelgium
  4. 4.French National Authority for Health-Transparency CommitteeParisFrance
  5. 5.International Osteoporosis FoundationNyonSwitzerland
  6. 6.Sanofi-AventisFrance
  7. 7.Wyeth ResearchPhiladelphiaUSA
  8. 8.Hôpital Edouard HerriotLyonFrance
  9. 9.Rhumatologie-Hôpital BichatParisFrance
  10. 10.Clinical Development, GSKPhiladelphiaUSA
  11. 11.Amgen Europe GmbHZugSwitzerland
  12. 12.UZ GentGentBelgium
  13. 13.Novartis Pharma AGBaselSwitzerland
  14. 14.Council for International Organisations of Medical SciencesGenevaSwitzerland
  15. 15.Austrian Medicines and Medical Devices AgencyViennaAustria
  16. 16.Eli Lilly & CoIndianapolisUSA
  17. 17.CHU Sart TilmanLiègeBelgium
  18. 18.Centre Collaborateur de l’Oms pour la prevention de l’osteoporoseGenevaSwitzerland
  19. 19.Merck & Co, IncWhitehouse StationUSA
  20. 20.F. Hoffman-La Roche LtdBaselSwitzerland
  21. 21.Institut de Recherches Internationales ServierParisFrance
  22. 22.Merck-TheramexMonacoMonaco
  23. 23.University of LiègeLiègeBelgium
  24. 24.Bone and Cartilage Metabolism Research UnitCHU Centre-Ville, Policliniques L. BRULLLiegeBelgium

Personalised recommendations