Incidence and Predictors of Multiple Fractures Despite High Adherence to Oral Bisphosphonates: A Binational Population-Based Cohort Study

S. Hawley, M.K. Javaid, K.H. Rubin, A. Judge, N.K. Arden, P. Vestergaard, R. Eastell, A. Diez-Perez, C. Cooper, B. Abrahamsen, D. Prieto-Alhambra

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Abstract

Oral bisphosphonates (BPs) are highly effective in preventing fractures and are recommended first-line therapies for patients with osteoporosis. We identified the incidence and predictors of oral BP treatment failure, defined as the incidence of two or more fractures while on treatment (≥2 FWOT) among users with high adherence. Fractures were considered from 6 months after treatment initiation and up to 6 months after discontinuation. Data from computerized records and pharmacy invoices were obtained from Sistema d'Informació per al Desenvolupament de l'Investigació en Atenció Primària (SIDIAP; Catalonia, Spain) and Danish Health Registries (Denmark) for all incident users of oral BPs in 2006-2007 and 2000-2001, respectively. Fine and Gray survival models using backward-stepwise selection (p-entry 0.049; p- exit 0.10) and accounting for the competing risk of therapy cessation were used to identify predictors of ≥2 FWOT among patients having persisted with treatment ≥6 months with overall medication possession ratio (MPR) ≥80%. Incidence of ≥2 FWOT was 2.4 (95% confidence interval [CI], 1.8 to 3.2) and 1.7 (95% CI, 1.2 to 2.2) per 1000 patient-years (PYs) within Catalonia and Denmark, respectively. Older age was predictive of ≥2 FWOT in both Catalonian and Danish cohorts: subhazard ratio (SHR) = 2.28 (95% CI, 1.11 to 4.68) and SHR = 2.61 (95% CI, 0.98 to 6.95), respectively, for 65 to
Original languageEnglish
Pages (from-to)234-244
Number of pages11
JournalJournal of Bone and Mineral Research
Volume31
Issue number1
DOIs
Publication statusPublished - Jan 2016

Keywords

  • Humans
  • Osteoporosis
  • Diphosphonates
  • Administration, Oral
  • Incidence
  • Survival Rate
  • Risk Factors
  • Follow-Up Studies
  • Aged
  • Aged, 80 and over
  • Middle Aged
  • Denmark
  • Spain
  • Female
  • Male
  • Medication Adherence
  • Fractures, Multiple

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