Osteoporosis International

, Volume 22, Issue 3, pp 943–954 | Cite as

Adherence to osteoporosis drugs and fracture prevention: no evidence of healthy adherer bias in a frail cohort of seniors

  • S. M. Cadarette
  • D. H. Solomon
  • J. N. Katz
  • A. R. Patrick
  • M. A. Brookhart
Original Article

Abstract

Summary

We examined new users of osteoporosis drugs among seniors in Pennsylvania and found no evidence of healthy adherer bias on observed associations between adherence to treatment and non-vertebral fracture risk; we document fracture reduction with better adherence to bisphosphonates, yet no fracture reduction with better adherence to calcitonin or raloxifene.

Introduction

We examined the potential for “healthy adherer bias” when studying the effects of adherence to osteoporosis pharmacotherapy on fracture risk. Based on clinical trial evidence, bisphosphonates, calcitonin, and raloxifene reduce vertebral fracture risk; yet only bisphosphonates are documented to reduce non-vertebral fracture risk.

Methods

This is a cohort study of older women in Pennsylvania who initiated osteoporosis drugs between 1995 and 2005. We included new users of bisphosphonates, calcitonin, and raloxifene. Adherence was categorized based on a measure of compliance as high [proportion of days covered (PDC) ≥ 80%], intermediate (50% < PDC < 80%), or low (PDC ≤ 50%) according to a 180-day ascertainment period. Non-vertebral fracture rates within 365 days after the ascertainment period were compared between adherence categories (reference = low) using Cox proportional hazard models and adjusting for fracture risk factors. Primary and secondary prevention cohorts were examined separately. Adherence to calcitonin and raloxifene were control analyses.

Results

We found little difference in fracture rates between levels of adherence to calcitonin, bisphosphonates for primary prevention, or raloxifene for secondary prevention. We document lower fracture rates among high versus low adherent bisphosphonate users for secondary prevention (HR = 0.53, 95%CI = 0.38–0.74) and higher fracture rates among high versus low adherent raloxifene users for primary prevention (HR = 2.01, 95%CI = 1.04–3.87).

Conclusions

We document little evidence of healthy adherer bias when studying the association between better adherence to osteoporosis drugs and fracture risk reduction, with only better adherence to bisphosphonates reducing fracture risk. The higher fracture risk among highly adherent raloxifene users for primary prevention is likely due to residual confounding.

Keywords

Bones Fractures Medication adherence Osteoporosis Selection bias 

References

  1. 1.
    Burge R, Dawson-Hughes B, Solomon DH et al (2007) Incidence and economic burden of osteoporosis-related fractures in the United States, 2005–2025. J Bone Miner Res 22:465–475CrossRefPubMedGoogle Scholar
  2. 2.
    MacLean C, Newberry S, Maglione M et al (2008) Systematic review: comparative effectiveness of treatments to prevent fractures in men and women with low bone density or osteoporosis. Ann Intern Med 148:197–213PubMedGoogle Scholar
  3. 3.
    Kothawala P, Badamgarav E, Ryu S et al (2007) Systematic review and meta-analysis of real-world adherence to drug therapy for osteoporosis. Mayo Clin Proc 82:1493–1501CrossRefPubMedGoogle Scholar
  4. 4.
    Siris ES, Selby PL, Saag KG et al (2009) Impact of osteoporosis treatment adherence on fracture rates in North America and Europe. Am J Med 122:S3–S13CrossRefPubMedGoogle Scholar
  5. 5.
    Wilkes MM, Navickis RJ, Chan WW et al (2010) Bisphosphonates and osteoporotic fractures: a cross-design synthesis of results among compliant/persistent postmenopausal women in clinical practice versus randomized controlled trials. Osteoporos Int 21:679–688CrossRefPubMedGoogle Scholar
  6. 6.
    Rabenda V, Hiligsmann M, Reginster JY (2009) Poor adherence to oral bisphosphonate treatment and its consequences: a review of the evidence. Expert Opin Pharmacother 10:2303–2315CrossRefPubMedGoogle Scholar
  7. 7.
    Imaz I, Zegarra P, Gonzalez-Enriquez J et al. (2010) Poor bisphosphonate adherence for treatment of osteoporosis increases fracture risk: systematic review and meta-analysis. Osteoporos Int. doi:10.1007/s00198-00009-01134-00194
  8. 8.
    Granger BB, Swedberg K, Ekman I et al (2005) Adherence to candesartan and placebo and outcomes in chronic heart failure in the CHARM programme: double-blind, randomised, controlled clinical trial. Lancet 366:2005–2011CrossRefPubMedGoogle Scholar
  9. 9.
    Simpson SH, Eurich DT, Majumdar SR et al (2006) A meta-analysis of the association between adherence to drug therapy and mortality. BMJ 333:15CrossRefPubMedGoogle Scholar
  10. 10.
    Curtis J, Larson J, Delzell E et al (2009) Does the benefit of medication adherence relate more to a drug effect or the behavior itself? Quantifying the effect of adherence behavior using data from the placebo arms of the WHI. Arthritis Rheum 60(Suppl 10):613 (abstract)Google Scholar
  11. 11.
    American College of Physicians (2008) Information on cost-effectiveness: an essential product of a national comparative effectiveness program. Ann Intern Med 148:956–961Google Scholar
  12. 12.
    Rasmussen JN, Chong A, Alter DA (2007) Relationship between adherence to evidence-based pharmacotherapy and long-term mortality after acute myocardial infarction. Jama 297:177–186CrossRefPubMedGoogle Scholar
  13. 13.
    Janz NK, Champion VL, Strecher VJ (2002) The health belief model. In: Glanz K, Rimer BK, Lewis FM (eds) Health behavior and health education: theory, research, and practice. Jossey-Bass, San Francisco, pp 45–66Google Scholar
  14. 14.
    DiMatteo MR, Haskard KB, Williams SL (2007) Health beliefs, disease severity, and patient adherence: a meta-analysis. Med Care 45:521–528CrossRefPubMedGoogle Scholar
  15. 15.
    Osterberg L, Blaschke T (2005) Adherence to medication. N Engl J Med 353:487–497CrossRefPubMedGoogle Scholar
  16. 16.
    Cramer JA, Roy A, Burrell A et al (2008) Medication compliance and persistence: terminology and definitions. Value Health 11:44–47PubMedGoogle Scholar
  17. 17.
    Peterson AM, Nau DP, Cramer JA et al (2007) A checklist for medication compliance and persistence studies using retrospective databases. Value Health 10:3–12CrossRefPubMedGoogle Scholar
  18. 18.
    Cadarette SM, Burden AM (2010) Measuring and improving adherence to osteoporosis pharmacotherapy. Curr Opin Rheumatol. doi:10.1097/BOR.0b013e32833ac7fe
  19. 19.
    Pols HA, Felsenberg D, Hanley DA et al (1999) Multinational, placebo-controlled, randomized trial of the effects of alendronate on bone density and fracture risk in postmenopausal women with low bone mass: results of the FOSIT Study. Fosamax International Trial Study Group. Osteoporos Int 9:461–468CrossRefPubMedGoogle Scholar
  20. 20.
    Suissa S (2008) Immeasurable time bias in observational studies of drug effects on mortality. Am J Epidemiol 2008:329–335CrossRefGoogle Scholar
  21. 21.
    Ray WA, Griffin MR, Fought RL et al (1992) Identification of fractures from computerized Medicare files. J Clin Epidemiol 45:703–714CrossRefPubMedGoogle Scholar
  22. 22.
    Cadarette SM, Katz JN, Brookhart MA et al (2008) Relative effectiveness of osteoporosis drugs for preventing nonvertebral fracture. Ann Intern Med 148:637–646PubMedGoogle Scholar
  23. 23.
    Foster SA, Foley KA, Meadows ES et al (2008) Characteristics of patients initiating raloxifene compared to those initiating bisphosphonates. BMC Womens Health 8:24CrossRefPubMedGoogle Scholar
  24. 24.
    Pickney CS, Arnason JA (2005) Correlation between patient recall of bone densitometry results and subsequent treatment adherence. Osteoporos Int 16:1156–1160CrossRefPubMedGoogle Scholar
  25. 25.
    Brookhart MA, Patrick AR, Avorn J et al (2007) Adherence to lipid-lowering therapy and the use of preventive health care services: an investigation of the healthy user effect. Am J Epidemiol 120:251–256Google Scholar
  26. 26.
    Dormuth CR, Patrick AR, Shrank WH et al (2009) Statin adherence and risk of accidents: a cautionary tale. Circulation 119:2051–2057CrossRefPubMedGoogle Scholar
  27. 27.
    Giangregorio L, Dolovich L, Cranney A et al (2009) Osteoporosis risk perceptions among patients who have sustained a fragility fracture. Patient Educ Couns 74:213–220CrossRefPubMedGoogle Scholar
  28. 28.
    Sale JEM, Beaton DE, Sujic R et al. (2010) “If it was osteoporosis, I would have really hurt myself.” Ambiguity about osteoporosis and osteoporosis care despite a screening program to educate fragility fracture patients. J Eval Clin Pract 16:590–596Google Scholar
  29. 29.
    Holick MF, Siris ES, Binkley N et al (2005) Prevalence of vitamin D inadequacy among postmenopausal North American women receiving osteoporosis therapy. J Clin Endocrinol Metab 90:3215–3224CrossRefPubMedGoogle Scholar
  30. 30.
    Miller PD, Derman RJ (2010) What is the best balance of benefits and risks among anti-resorptive therapies for postmenopausal osteoporosis? Osteoporos Int. doi:10.1007/s00198-010-1208-3
  31. 31.
    Brookhart MA, Avorn J, Katz JN et al (2007) Gaps in treatment among users of osteoporosis medications: the dynamics of noncompliance. Am J Med 120:251–256CrossRefPubMedGoogle Scholar
  32. 32.
    Roughead EE, Ramsay E, Priess K et al (2009) Medication adherence, first episode duration, overall duration and time without therapy: the example of bisphosphonates. Pharmacoepidemiol Drug Saf 18:69–75CrossRefPubMedGoogle Scholar

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2010

Authors and Affiliations

  • S. M. Cadarette
    • 1
    • 2
    • 3
  • D. H. Solomon
    • 2
    • 3
    • 4
  • J. N. Katz
    • 3
    • 4
    • 5
  • A. R. Patrick
    • 3
    • 2
  • M. A. Brookhart
    • 2
    • 3
    • 6
  1. 1.Leslie Dan Faculty of PharmacyUniversity of TorontoTorontoCanada
  2. 2.Division of Pharmacoepidemiology and PharmacoeconomicsBrigham and Women’s HospitalBostonUSA
  3. 3.Harvard Medical SchoolBostonUSA
  4. 4.Division of Rheumatology, Immunology and AllergyBrigham and Women’s HospitalBostonUSA
  5. 5.Department of Orthopedic SurgeryBrigham and Women’s HospitalBostonUSA
  6. 6.Department of Epidemiology, Gillings School of Global Public HealthUniversity of North Carolina at Chapel HillChapel HillUSA

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