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


BACKGROUND
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.
Leslie Dan Faculty of Pharmacy, University of Toronto, 144 College Street, Toronto, ON, Canada M5S3M2. s.cadarette@utoronto.ca
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Cadarette
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Solomon
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Katz
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Patrick
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Brookhart
D000368:Aged; D000369:Aged, 80 and over; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D002116:Calcitonin / Q000627:therapeutic use; D004164:Diphosphonates / Q000627:therapeutic use; D005260:Female; D016330:Frail Elderly; D006620:Hip Fractures / Q000453:epidemiology / Q000517:prevention & control; D006801:Humans; D006811:Humerus / Q000293:injuries; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy*; D058866:Osteoporotic Fractures / Q000453:epidemiology / Q000517:prevention & control*; D010349:Patient Compliance / Q000706:statistics & numerical data*; D010414:Pennsylvania / Q000453:epidemiology; D011885:Radius Fractures / Q000453:epidemiology / Q000517:prevention & control; D020849:Raloxifene Hydrochloride / Q000627:therapeutic use; D014458:Ulna Fractures / Q000453:epidemiology / Q000517:prevention & control
D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D020849:Raloxifene Hydrochloride; D002116:Calcitonin