SpringerLink
Log in

Role of Side Effects, Physician Involvement, and Patient Perception in Non-Adherence with Oral Bisphosphonates

  • Original Research
  • Published:
Advances in Therapy Aims and scope Submit manuscript

Abstract

Introduction

The benefits of osteoporosis therapy are compromised by low adherence, thus requiring a better understanding of its barriers and unmet needs. The objective of this study was to assess reasons for non-adherence with oral bisphosphonates among osteoporotic women.

Methods

A cross-sectional patient survey of women who initiated therapy with risedronate or alendronate between the years 2010 and 2012 were non-adherent [Medication Possession Ratio (MPR) <70%] or switched therapy within the first year. Survey participants were identified using Maccabi Health Services computerized database. Patients who gave informed consent completed a 20-min telephonic survey, assessing reasons for discontinuation or switching, including physician involvement, side effects, administration regimen, perceptions of bone health, and medications’ efficacy.

Results

The study population included 493 females (mean age = 66 ± 7) of whom 40% discontinued all anti-osteoporotic therapy (mean MPR = 19%), 9% remained on initial therapy (mean MPR = 47%), and 51% switched therapy (mean MPR = 62%). Family history, fracture history, socioeconomic status, and index drug class and frequency were similar in all groups. The most common reasons for switching or discontinuation of the first-line therapy were gastrointestinal side effects, such as heartburn, acid reflux or other (40.0%), and physician recommendation (26.7%). The major reasons for complete discontinuation of therapy were side effects (26.9%) and physician recommendation (20.0%). Perceived low importance was more commonly mentioned than high cost of medication (14% vs. 3%).

Conclusion

Our findings highlight the importance of low tolerability to non-adherence with osteoporosis therapy and underlines poor patients’ awareness and sub-optimal physicians’ involvement in conveying the importance of this therapy.

Funding

Merck & Co Inc.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price includes VAT (Germany)

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Kanis JA, Melton LR, Christiansen C, Johnston CC, Khaltaev N. The diagnosis of osteoporosis. J Bone Miner Res. 1994;9(8):1137–41.

    Article  CAS  PubMed  Google Scholar 

  2. MacLean C, Newberry S, Maglione M, et al. Systematic review: comparative effectiveness of treatments to prevent fractures in men and women with low bone density or osteoporosis. Ann Intern Med. 2008;148(3):197–213.

    Article  PubMed  Google Scholar 

  3. Hadji P, Claus V, Ziller V, Intorcia M, Kostev K, Steinle T. GRAND: the German retrospective cohort analysis on compliance and persistence and the associated risk of fractures in osteoporotic women treated with oral bisphosphonates. Osteoporos Int. 2012;23(1):223–31.

    Article  CAS  PubMed  Google Scholar 

  4. Imaz I, Zegarra P, Gonzalez-Enriquez J, Rubio B, Alcazar R, Amate JM. Poor bisphosphonate adherence for treatment of osteoporosis increases fracture risk: systematic review and meta-analysis. Osteoporos Int. 2010;21(11):1943–51.

    Article  CAS  PubMed  Google Scholar 

  5. Huybrechts KF, Ishak KJ, Caro JJ. Assessment of compliance with osteoporosis treatment and its consequences in a managed care population. Bone. 2006;38(6):922–8.

    Article  PubMed  Google Scholar 

  6. Rabenda V, Hiligsmann M, Reginster JY. Poor adherence to oral bisphosphonate treatment and its consequences: a review of the evidence. Expert Opin Pharmacother. 2009;10(14):2303–15.

    Article  CAS  PubMed  Google Scholar 

  7. Yeaw J, Benner JS, Walt JG, Sian S, Smith DB. Comparing adherence and persistence across 6 chronic medication classes. J Managed Care Pharm JMCP. 2009;15(9):728–40.

    Article  PubMed  Google Scholar 

  8. 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(8):1013–22.

    Article  PubMed  Google Scholar 

  9. Rabenda V, Mertens R, Fabri V, et al. Adherence to bisphosphonates therapy and hip fracture risk in osteoporotic women. Osteoporos Int. 2008;19(6):811–8.

    Article  CAS  PubMed  Google Scholar 

  10. Siris ES, Selby PL, Saag KG, Borgstrom F, Herings RM, Silverman SL. Impact of osteoporosis treatment adherence on fracture rates in North America and Europe. Am J Med. 2009;122(2 Suppl):S3–13.

    Article  PubMed  Google Scholar 

  11. Ross S, Samuels E, Gairy K, Iqbal S, Badamgarav E, Siris E. A meta-analysis of osteoporotic fracture risk with medication nonadherence. Value Health. 2011;14(4):571–81.

    Article  PubMed  Google Scholar 

  12. Hiligsmann M, Rabenda V, Bruyere O, Reginster JY. The clinical and economic burden of non-adherence with oral bisphosphonates in osteoporotic patients. Health Policy. 2010;96(2):170–7.

    Article  PubMed  Google Scholar 

  13. Mukhtar O, Weinman J, Jackson SH. Intentional non-adherence to medications by older adults. Drugs Aging. 2014;31(3):149–57.

    Article  PubMed  Google Scholar 

  14. Horne R, Weinman J, Hankins M. The beliefs about medicines questionnaire: the development and evaluation of a new method for assessing the cognitive representation of medication. Psychol Health. 1999;14(1):1–24.

    Article  Google Scholar 

  15. Reynolds K, Viswanathan HN, Muntner P, et al. Validation of the Osteoporosis-Specific Morisky Medication Adherence Scale in long-term users of bisphosphonates. Qual Life Res. 2014;23(7):2109–20.

    Article  PubMed  Google Scholar 

  16. Flood EM, Beusterien KM, Green H, et al. Psychometric evaluation of the Osteoporosis Patient Treatment Satisfaction Questionnaire (OPSAT-Q), a novel measure to assess satisfaction with bisphosphonate treatment in postmenopausal women. Health Qual Life Outcomes. 2006;4:42.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Chandler JM, Martin AR, Girman C, et al. Reliability of an Osteoporosis-Targeted Quality of Life Survey Instrument for use in the community: OPTQoL. Osteoporos Int. 1998;8(2):127–35.

    Article  CAS  PubMed  Google Scholar 

  18. Hamilton B, McCoy K, Taggart H. Tolerability and compliance with risedronate in clinical practice. Osteoporos Int. 2003;14(3):259–62.

    CAS  PubMed  Google Scholar 

  19. 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(2):245–56.

    Article  CAS  PubMed  Google Scholar 

  20. McHorney CA, Schousboe JT, Cline RR, Weiss TW. The impact of osteoporosis medication beliefs and side-effect experiences on non-adherence to oral bisphosphonates. Curr Med Res Opin. 2007;23(12):3137–52.

    Article  CAS  PubMed  Google Scholar 

  21. Woo C, Gao G, Wade S, Hochberg MC. Gastrointestinal side effects in postmenopausal women using osteoporosis therapy: 1-year findings in the POSSIBLE US study. Curr Med Res Opin. 2010;26(4):1003–9.

    Article  Google Scholar 

  22. Shane E, Burr D, Ebeling PR, et al. Atypical subtrochanteric and diaphyseal femoral fractures: report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res. 2010;25(11):2267–94.

    Article  PubMed  Google Scholar 

  23. Shane E, Burr D, Abrahamsen B, et al. Atypical subtrochanteric and diaphyseal femoral fractures: second report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res. 2014;29(1):1–23.

    Article  PubMed  Google Scholar 

  24. Khosla S, Burr D, Cauley J, et al. Bisphosphonate-associated osteonecrosis of the jaw: report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res. 2007;22(10):1479–91.

    Article  PubMed  Google Scholar 

  25. Silverman SL, Landesberg R. Osteonecrosis of the jaw and the role of bisphosphonates: a critical review. Am J Med. 2009;122(2 Suppl):S33–45.

    Article  CAS  PubMed  Google Scholar 

  26. Reid IR. Short-term and long-term effects of osteoporosis therapies. Nat Rev Endocrinol. 2015;11(7):418–28.

    Article  CAS  PubMed  Google Scholar 

  27. Hiligsmann M, Salas M, Hughes DA, et al. Interventions to improve osteoporosis medication adherence and persistence: a systematic review and literature appraisal by the ISPOR Medication Adherence and Persistence Special Interest Group. Osteoporos Int. 2013;24(12):2907–18.

    Article  CAS  PubMed  Google Scholar 

  28. Nielsen D, Ryg J, Nielsen W, Knold B, Nissen N, Brixen K. Patient education in groups increases knowledge of osteoporosis and adherence to treatment: a two-year randomized controlled trial. Patient Educ Couns. 2010;81(2):155–60.

    Article  PubMed  Google Scholar 

  29. Cook PF, Emiliozzi S, McCabe MM. Telephone counseling to improve osteoporosis treatment adherence: an effectiveness study in community practice settings. Am J Med Qual. 2007;22(6):445–56.

    Article  PubMed  Google Scholar 

  30. Solomon DH, Katz JN, Finkelstein JS, et al. Osteoporosis improvement: a large-scale randomized controlled trial of patient and primary care physician education. J Bone Miner Res. 2007;22(11):1808–15.

    Article  PubMed  Google Scholar 

  31. Shu AD, Stedman MR, Polinski JM, et al. Adherence to osteoporosis medications after patient and physician brief education: post hoc analysis of a randomized controlled trial. Am J Manag Care. 2009;15(7):417–24.

    PubMed  PubMed Central  Google Scholar 

  32. 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(3):1117–23.

    Article  CAS  PubMed  Google Scholar 

  33. Delmas PD, Vrijens B, Eastell R, et al. Effect of monitoring bone turnover markers on persistence with risedronate treatment of postmenopausal osteoporosis. J Clin Endocrinol Metab. 2007;92(4):1296–304.

    Article  CAS  PubMed  Google Scholar 

  34. Pickney CS, Arnason JA. Correlation between patient recall of bone densitometry results and subsequent treatment adherence. Osteoporos Int. 2005;16(9):1156–60.

    Article  PubMed  Google Scholar 

  35. Silverman SL, Nasser K, Nattrass S, Drinkwater B. Impact of bone turnover markers and/or educational information on persistence to oral bisphosphonate therapy: a community setting-based trial. Osteoporos Int. 2012;23(3):1069–74.

    Article  CAS  PubMed  Google Scholar 

  36. Compston J. Monitoring osteoporosis treatment. Best Pract Res Clin Rheumatol. 2009;23(6):781–8.

    Article  PubMed  Google Scholar 

  37. Cooper A. Compliance with treatment for osteoporosis. Lancet. 2006;368(9548):1648.

    Article  PubMed  Google Scholar 

  38. Kendler DL, McClung MR, Freemantle N, et al. Adherence, preference, and satisfaction of postmenopausal women taking denosumab or alendronate. Osteoporos Int. 2011;22(6):1725–35.

    Article  CAS  PubMed  Google Scholar 

  39. Freemantle N, Satram-Hoang S, Tang ET, et al. Final results of the DAPS (Denosumab Adherence Preference Satisfaction) study: a 24-month, randomized, crossover comparison with alendronate in postmenopausal women. Osteoporos Int. 2012;23(1):317–26.

    Article  CAS  PubMed  Google Scholar 

  40. Cotte FE, Fardellone P, Mercier F, Gaudin AF, Roux C. Adherence to monthly and weekly oral bisphosphonates in women with osteoporosis. Osteoporos Int. 2010;21(1):145–55.

    Article  CAS  PubMed  Google Scholar 

  41. Hill DA, Cacciatore M, Lamvu GM. Electronic prescribing influence on calcium supplementation: a randomized controlled trial. Am J Obstetr Gynecol. 2010;202(3):236.

    Article  Google Scholar 

  42. Alamri SH, Kennedy CC, Marr S, Lohfeld L, Skidmore CJ, Papaioannou A. Strategies to overcome barriers to implementing osteoporosis and fracture prevention guidelines in long-term care: a qualitative analysis of action plans suggested by front line staff in Ontario, Canada. BMC Geriatr. 2015;15:94.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Reginster JY, Neuprez A, Lecart MP, et al. Osteoporosis and personalized medicine. Rev Med Liege. 2015;70(5–6):321–4.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

Sponsorship and article processing charges for this study were funded by Merck and co. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this manuscript, take responsibility for the integrity of the work as a whole, and have given final approval for the version to be published.

Disclosures

Inbal Goldshtein, Vanessa Rouach, Naama Shamir-Stein, and Gabriel Chodick have nothing to disclose. **gbo Yu was a Merck employee at the time of the study.

Compliance with Ethics Guidelines

The study protocol was approved by the MHS and Assuta Health Systems ethical review board. All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1964, as revised in 2013. Informed consent was obtained from all patients for being included in the study.

Author information

Author notes

    Authors and Affiliations

    1. Epidemiology and Database Research Unit, Maccabi Healthcare Services, Tel Aviv, Israel

      Inbal Goldshtein, Vanessa Rouach & Gabriel Chodick

    2. Tel Aviv University, Tel Aviv, Israel

      Inbal Goldshtein & Gabriel Chodick

    3. Institute of Hypertension, Metabolism, and Endocrinology, Tel Aviv Souraski Medical Center, Tel Aviv, Israel

      Vanessa Rouach

    4. Research and Evaluation Department, Maccabi Healthcare Services, Tel Aviv, Israel

      Naama Shamir-Stein

    5. Merck & Co, Inc, Kenilworth, NJ, USA

      **gbo Yu

    Authors
    1. Inbal Goldshtein
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Vanessa Rouach
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Naama Shamir-Stein
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. **gbo Yu
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Gabriel Chodick
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding author

    Correspondence to Inbal Goldshtein.

    Additional information

    Inbal Goldshtein and Vanessa Rouach contributed equally to this work.

    Enhanced content

    To view enhanced content for this article go to www.medengine.com/Redeem/B9D4F06065B72F60.

    Electronic supplementary material

    Below is the link to the electronic supplementary material.

    Supplementary material 1 (PDF 195 kb)

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Goldshtein, I., Rouach, V., Shamir-Stein, N. et al. Role of Side Effects, Physician Involvement, and Patient Perception in Non-Adherence with Oral Bisphosphonates. Adv Ther 33, 1374–1384 (2016). https://doi.org/10.1007/s12325-016-0360-3

    Download citation

    • Received:

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s12325-016-0360-3

    Keywords

    Search

    Navigation