Dr. Curtis has received consultant fees and/or honoraria (less than $10,000 each) from Merck, Lilly, and (more than $10,000) from Amgen.
Does medication adherence itself confer fracture protection? An investigation of the healthy adherer effect in observational data
Article first published online: 28 NOV 2012
Copyright © 2012 by the American College of Rheumatology
Arthritis Care & Research
Volume 64, Issue 12, pages 1855–1863, December 2012
How to Cite
Curtis, J. R., Yun, H., Lange, J. L., Matthews, R., Sharma, P., Saag, K. G. and Delzell, E. (2012), Does medication adherence itself confer fracture protection? An investigation of the healthy adherer effect in observational data. Arthritis Care Res, 64: 1855–1863. doi: 10.1002/acr.21759
- Issue published online: 28 NOV 2012
- Article first published online: 28 NOV 2012
- Accepted manuscript online: 21 JUN 2012 09:14AM EST
- Manuscript Accepted: 7 JUN 2012
- Manuscript Received: 7 FEB 2012
- Contract between the University of Alabama at Birmingham and Amgen
- NIH. Grant Number: AR-053351
- Agency for Healthcare Research and Quality. Grant Number: R01-HS018517
- NIH. Grant Number: AR-052361
- Agency for Healthcare Research and Quality. Grant Number: U18-HS016956
Prior observational studies have shown an association between bisphosphonate adherence and fewer fractures. It is unclear if such studies reflect pharmacologic benefits or behavioral attributes, i.e., the healthy adherer effect. Our objective was to examine the association of therapy adherence and fracture risk among patients initiating therapies hypothesized to be favorable, unfavorable, or neutral toward fracture risk, in order to evaluate for a healthy adherer effect.
In this observational study, we identified patients within Medicare 2006–2009 data who initiated any of 3 medication groups within 9 months after an osteoporotic fracture as follows: 1) oral bisphosphonates (n = 2,507), 2) selective serotonin reuptake inhibitors (SSRIs; n = 2,420), or 3) angiotensin-converting enzyme (ACE) inhibitor or calcium-channel blocker (CCB; n = 2,178). Cox regression analysis, adjusting for covariates, was used to compare fracture rates at the hip and major osteoporotic fracture sites (including hip, clinical vertebral, humerus, and wrist) during followup, comparing patients with high adherence versus low adherence within each medication group.
There were few baseline differences between those who had high adherence versus lower adherence. High adherence with bisphosphonates decreased fracture risk at both hip (hazard ratio [HR] 0.53, 95% confidence interval [95% CI] 0.32–0.96) and major fracture sites (HR 0.61, 95% CI 0.45–0.80). High adherence with SSRIs suggested increased fracture risk at both hip (HR 1.58, 95% CI 0.97–2.57) and major fracture sites (HR 1.32, 95% CI 0.96–1.83). High adherence with ACE inhibitors/CCBs was neutral toward fracture risk at both hip (HR 1.27, 95% CI 0.67–2.41) and major fracture sites (HR 1.00, 95% CI 0.67–1.49).
In this observational cohort of older individuals, the association between medication adherence and fracture risk differed by medication exposure, suggesting a limited role for the healthy adherer effect in observational studies of osteoporosis medications.