title: Residual effect after oral bisphosphonate treatment and healthy adherer effects--the Swedish Adherence Register Analysis (SARA).
abstract: Little is known of the effect of alendronate and risedronate on osteoporotic fractures after discontinuation of therapy. We found that time on treatment was significantly inversely associated with the incidence of hospitalized fractures during posttreatment follow-up. Our results will inform health economic analysis of osteoporosis interventions.
  
  
  BACKGROUND
  Real-world persistence to treatment of osteoporosis is well-understood, but little is known of the posttreatment residual effect on fractures. The objective of this study was to investigate the residual effect of alendronate and risedronate on fractures and assess whether a healthy adherer effect confounds the association between persistence and residual anti-fracture effect.
  
  
  METHODS
  A treatment-naïve cohort from the Swedish Prescribed Drug Register was identified through prescriptions for alendronate or risedronate between 2005 and 2009. Persistence was estimated, and patients were stratified by time on treatment (<1 month, 1-6 months, 7-12 months, and >12 months). Survival analysis was used to study hospitalized fractures and mortality up to 18 months after treatment discontinuation.
  
  
  RESULTS
  The crude incidence proportion of fractures the first 6 months after treatment discontinuation ranged from 2.26% (<1 month of treatment) to 1.16% (>12 months). The corresponding estimates for month 7 to 12 after discontinuation was 3.18 to 1.96%, and for month 13 to 18 after discontinuation 2.69 to 1.95%. Adjusted regression results showed that patients persisting with therapy for >12 months had 60% lower fracture risk the first six months after treatment discontinuation (RR 0.40, p = 0.001). Patient characteristics, including prevalent fractures and co-morbidities, and posttreatment mortality were comparable across persistence durations, and we found no evidence of a healthy adherer effect.
  
  
  CONCLUSIONS
  Time on bisphosphonate treatment was significantly inversely associated with the incidence of hospitalized fractures during posttreatment follow-up. We found no evidence of a healthy adherer effect confounding the relationship between treatment persistence and fracture risk.
authors.affiliation: Department of Learning, Informatics, Management, and Ethics, Karolinska Institutet, Hantverkargatan 8, 112 21, Stockholm, Sweden, oskar.strom@ki.se.
authors.forename: O
authors.initials: O
authors.lastname: Ström
authors.forename: E
authors.initials: E
authors.lastname: Landfeldt
authors.forename: G
authors.initials: G
authors.lastname: Garellick
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D019386:Alendronate / Q000008:administration & dosage* / Q000627:therapeutic use; D050071:Bone Density Conservation Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D015897:Comorbidity; D015987:Effect Modifier, Epidemiologic; D012968:Etidronic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000188:drug therapy* / Q000453:epidemiology; D058866:Osteoporotic Fractures / Q000453:epidemiology / Q000517:prevention & control; D012042:Registries; D000068296:Risedronic Acid; D018570:Risk Assessment / Q000379:methods; D013548:Sweden / Q000453:epidemiology; D028761:Withholding Treatment; D016903:Drug Monitoring
chemical_list: D050071:Bone Density Conservation Agents; D000068296:Risedronic Acid; D012968:Etidronic Acid; D019386:Alendronate