Skip to main content
Top
Published in: Osteoporosis International 3/2011

01-03-2011 | Original Article

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

Authors: S. M. Cadarette, D. H. Solomon, J. N. Katz, A. R. Patrick, M. A. Brookhart

Published in: Osteoporosis International | Issue 3/2011

Login to get access

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.
Appendix
Available only for authorised users
Literature
1.
go back to reference 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 22:465–475CrossRefPubMed 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 22:465–475CrossRefPubMed
2.
go back to reference 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 148:197–213PubMed 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 148:197–213PubMed
3.
go back to reference 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 82:1493–1501CrossRefPubMed 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 82:1493–1501CrossRefPubMed
4.
go back to reference 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–S13CrossRefPubMed 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–S13CrossRefPubMed
5.
go back to reference 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 21:679–688CrossRefPubMed 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 21:679–688CrossRefPubMed
6.
go back to reference Rabenda V, Hiligsmann M, Reginster JY (2009) Poor adherence to oral bisphosphonate treatment and its consequences: a review of the evidence. Expert Opin Pharmacother 10:2303–2315CrossRefPubMed Rabenda V, Hiligsmann M, Reginster JY (2009) Poor adherence to oral bisphosphonate treatment and its consequences: a review of the evidence. Expert Opin Pharmacother 10:2303–2315CrossRefPubMed
7.
go back to reference 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 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.
go back to reference 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 366:2005–2011CrossRefPubMed 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 366:2005–2011CrossRefPubMed
9.
go back to reference Simpson SH, Eurich DT, Majumdar SR et al (2006) A meta-analysis of the association between adherence to drug therapy and mortality. BMJ 333:15CrossRefPubMed Simpson SH, Eurich DT, Majumdar SR et al (2006) A meta-analysis of the association between adherence to drug therapy and mortality. BMJ 333:15CrossRefPubMed
10.
go back to reference 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) 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)
11.
go back to reference American College of Physicians (2008) Information on cost-effectiveness: an essential product of a national comparative effectiveness program. Ann Intern Med 148:956–961 American College of Physicians (2008) Information on cost-effectiveness: an essential product of a national comparative effectiveness program. Ann Intern Med 148:956–961
12.
go back to reference Rasmussen JN, Chong A, Alter DA (2007) Relationship between adherence to evidence-based pharmacotherapy and long-term mortality after acute myocardial infarction. Jama 297:177–186CrossRefPubMed Rasmussen JN, Chong A, Alter DA (2007) Relationship between adherence to evidence-based pharmacotherapy and long-term mortality after acute myocardial infarction. Jama 297:177–186CrossRefPubMed
13.
go back to reference 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 45–66 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 45–66
14.
go back to reference DiMatteo MR, Haskard KB, Williams SL (2007) Health beliefs, disease severity, and patient adherence: a meta-analysis. Med Care 45:521–528CrossRefPubMed DiMatteo MR, Haskard KB, Williams SL (2007) Health beliefs, disease severity, and patient adherence: a meta-analysis. Med Care 45:521–528CrossRefPubMed
16.
go back to reference Cramer JA, Roy A, Burrell A et al (2008) Medication compliance and persistence: terminology and definitions. Value Health 11:44–47PubMed Cramer JA, Roy A, Burrell A et al (2008) Medication compliance and persistence: terminology and definitions. Value Health 11:44–47PubMed
17.
go back to reference Peterson AM, Nau DP, Cramer JA et al (2007) A checklist for medication compliance and persistence studies using retrospective databases. Value Health 10:3–12CrossRefPubMed Peterson AM, Nau DP, Cramer JA et al (2007) A checklist for medication compliance and persistence studies using retrospective databases. Value Health 10:3–12CrossRefPubMed
19.
go back to reference 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 9:461–468CrossRefPubMed 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 9:461–468CrossRefPubMed
20.
go back to reference Suissa S (2008) Immeasurable time bias in observational studies of drug effects on mortality. Am J Epidemiol 2008:329–335CrossRef Suissa S (2008) Immeasurable time bias in observational studies of drug effects on mortality. Am J Epidemiol 2008:329–335CrossRef
21.
go back to reference Ray WA, Griffin MR, Fought RL et al (1992) Identification of fractures from computerized Medicare files. J Clin Epidemiol 45:703–714CrossRefPubMed Ray WA, Griffin MR, Fought RL et al (1992) Identification of fractures from computerized Medicare files. J Clin Epidemiol 45:703–714CrossRefPubMed
22.
go back to reference Cadarette SM, Katz JN, Brookhart MA et al (2008) Relative effectiveness of osteoporosis drugs for preventing nonvertebral fracture. Ann Intern Med 148:637–646PubMed Cadarette SM, Katz JN, Brookhart MA et al (2008) Relative effectiveness of osteoporosis drugs for preventing nonvertebral fracture. Ann Intern Med 148:637–646PubMed
23.
go back to reference Foster SA, Foley KA, Meadows ES et al (2008) Characteristics of patients initiating raloxifene compared to those initiating bisphosphonates. BMC Womens Health 8:24CrossRefPubMed Foster SA, Foley KA, Meadows ES et al (2008) Characteristics of patients initiating raloxifene compared to those initiating bisphosphonates. BMC Womens Health 8:24CrossRefPubMed
24.
go back to reference Pickney CS, Arnason JA (2005) Correlation between patient recall of bone densitometry results and subsequent treatment adherence. Osteoporos Int 16:1156–1160CrossRefPubMed Pickney CS, Arnason JA (2005) Correlation between patient recall of bone densitometry results and subsequent treatment adherence. Osteoporos Int 16:1156–1160CrossRefPubMed
25.
go back to reference 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 120:251–256 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 120:251–256
26.
go back to reference Dormuth CR, Patrick AR, Shrank WH et al (2009) Statin adherence and risk of accidents: a cautionary tale. Circulation 119:2051–2057CrossRefPubMed Dormuth CR, Patrick AR, Shrank WH et al (2009) Statin adherence and risk of accidents: a cautionary tale. Circulation 119:2051–2057CrossRefPubMed
27.
go back to reference Giangregorio L, Dolovich L, Cranney A et al (2009) Osteoporosis risk perceptions among patients who have sustained a fragility fracture. Patient Educ Couns 74:213–220CrossRefPubMed Giangregorio L, Dolovich L, Cranney A et al (2009) Osteoporosis risk perceptions among patients who have sustained a fragility fracture. Patient Educ Couns 74:213–220CrossRefPubMed
28.
go back to reference 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 16:590–596 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 16:590–596
29.
go back to reference 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 90:3215–3224CrossRefPubMed 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 90:3215–3224CrossRefPubMed
30.
go back to reference 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 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.
go back to reference Brookhart MA, Avorn J, Katz JN et al (2007) Gaps in treatment among users of osteoporosis medications: the dynamics of noncompliance. Am J Med 120:251–256CrossRefPubMed Brookhart MA, Avorn J, Katz JN et al (2007) Gaps in treatment among users of osteoporosis medications: the dynamics of noncompliance. Am J Med 120:251–256CrossRefPubMed
32.
go back to reference 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 18:69–75CrossRefPubMed 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 18:69–75CrossRefPubMed
Metadata
Title
Adherence to osteoporosis drugs and fracture prevention: no evidence of healthy adherer bias in a frail cohort of seniors
Authors
S. M. Cadarette
D. H. Solomon
J. N. Katz
A. R. Patrick
M. A. Brookhart
Publication date
01-03-2011
Publisher
Springer-Verlag
Published in
Osteoporosis International / Issue 3/2011
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-010-1309-z

Other articles of this Issue 3/2011

Osteoporosis International 3/2011 Go to the issue