Does medication adherence itself confer fracture protection? An investigation of the healthy adherer effect in observational data.
OBJECTIVE
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
University of Alabama at Birmingham, Birmingham, AL 35294, USA. jcurtis@uab.edu
Jeffrey R
JR
Curtis
Huifeng
H
Yun
Jeff L
JL
Lange
Robert
R
Matthews
Pradeep
P
Sharma
Kenneth G
KG
Saag
Elizabeth
E
Delzell
D000368:Aged; D000369:Aged, 80 and over; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D015331:Cohort Studies; D015986:Confounding Factors, Epidemiologic; D004164:Diphosphonates / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D055118:Medication Adherence / Q000523:psychology*; D010024:Osteoporosis / Q000188:drug therapy / Q000523:psychology*; D058866:Osteoporotic Fractures / Q000453:epidemiology* / Q000517:prevention & control / Q000523:psychology; D017063:Outcome Assessment, Health Care / Q000379:methods*; D012307:Risk Factors; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use; D014481:United States / Q000453:epidemiology
D000806:Angiotensin-Converting Enzyme Inhibitors; D002121:Calcium Channel Blockers; D004164:Diphosphonates; D017367:Selective Serotonin Reuptake Inhibitors