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



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.


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.


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.


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).


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.


Bones Fractures Medication adherence Osteoporosis Selection bias 


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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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