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

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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.

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Acknowledgments

The authors thank Raisa Levin for preparing the study data for analysis and kindly acknowledge helpful discussions with Drs. Jerry Avorn and Robert J. Glynn, Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women’s Hospital, Harvard Medical School. Dr Brookhart is supported by the National Institute on Aging (K25 AG027400), Dr Cadarette is supported by the Canadian Institutes of Health Research (New Investigator Award in the Area of Aging and Osteoporosis, MSH95364), Dr Katz is supported by the National Institute of Arthritis and Muskuloskeletal and Skin Diseases (K24 AR02123 and P60 AR47782), and Dr Solomon is supported by the Arthritis Foundation and the National Institutes of Health (K24 AR055989, R21 AG027066 and P60 AR47782).

Conflicts of interest

Co-authors have received salary support for research grants awarded to the Brigham and Women’s Hospital for unrelated work from: Amgen (Drs Brookhart and Solomon) and Novartis (Dr Solomon). There was no pharmaceutical industry support for this study.

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Correspondence to S. M. Cadarette.

Appendix

Appendix

Table 3 Study outcome coding (diagnostic and procedural codes)
Table 4 Coding of covariates in baseline period—all included when studying fracture risk
Fig. 3
figure 3

Flow diagram of participant inclusion—enrollees in the Pennsylvania Pharmaceutical Assistance Contract for the Elderly (PACE). *subcategories for exclusion are not mutually exclusive

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Cadarette, S.M., Solomon, D.H., Katz, J.N. et al. Adherence to osteoporosis drugs and fracture prevention: no evidence of healthy adherer bias in a frail cohort of seniors. Osteoporos Int 22, 943–954 (2011). https://doi.org/10.1007/s00198-010-1309-z

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  • DOI: https://doi.org/10.1007/s00198-010-1309-z

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