title: Biologic disease-modifying anti-rheumatic drugs and the risk of non-vertebral osteoporotic fractures in patients with rheumatoid arthritis aged 50 years and over.
abstract: Prevention of bone mineral density loss in rheumatoid arthritis (RA) has been associated with use of biologic disease-modifying anti-rheumatic drugs (DMARDs). However, in this study, we could not demonstrate a reduction in the risk of non-vertebral fractures. Additional research is required to clarify the impact of biologic DMARDs on fracture risk in RA.
  
  
  BACKGROUND
  Small studies have suggested biologic DMARDs preserve bone mineral density at 6-12 months. Our objective was to determine the association between biologic DMARD use and the risk of non-vertebral osteoporotic fractures in RA subjects aged ≥50 years.
  
  
  METHODS
  A nested case-control study was conducted using Quebec physician billing and hospital discharge data. RA subjects were identified from International Classification of Disease-9/10 codes in billing and hospitalisation data and followed from cohort entry until the earliest of non-vertebral osteoporotic fracture, death, or end of study period. Controls were matched to cases (4:1 ratio) on age, sex, and date of cohort entry. Biologic DMARD exposure was defined as being on treatment for ≥180 days pre-fracture (index). Conditional logistic regression was used, adjusting for indicators of RA severity, comorbidity, drugs influencing fracture risk, and measures of health care utilisation.
  
  
  RESULTS
  Over the study period, 1,515 cases were identified (6,023 controls). The most frequent fracture site was hip/femur (42.3%). In total, 172 subjects (49 cases and 123 controls) were exposed to biologic DMARDs. The median duration of exposure was 735 (interquartile range (IQR), 564) and 645 (IQR, 903) days in cases and controls, respectively. We were unable to demonstrate an association between biologic DMARDs and fracture risk (odds ratio, 1.03; 95% confidence interval, 0.42-2.53). RA duration significantly increased the fracture risk.
  
  
  CONCLUSIONS
  Despite the positive impact of biologic DMARDs on bone remodelling observed in small studies, we were unable to demonstrate a reduction in the risk of non-vertebral osteoporotic fractures in older adults with RA.
authors.affiliation: Faculty of Pharmacy, University of Montreal, Pavillon Jean-Coutu, 2940 chemin de la polytechnique, Montreal, QC, Canada, H3C 3J7.
authors.forename: J-P
authors.initials: JP
authors.lastname: Roussy
authors.forename: L
authors.initials: L
authors.lastname: Bessette
authors.forename: S
authors.initials: S
authors.lastname: Bernatsky
authors.forename: E
authors.initials: E
authors.lastname: Rahme
authors.forename: J
authors.initials: J
authors.lastname: Lachaine
mesh_terms: D000368:Aged; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000453:epidemiology; D001688:Biological Products / Q000008:administration & dosage / Q000627:therapeutic use*; D016022:Case-Control Studies; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D058866:Osteoporotic Fractures / Q000453:epidemiology / Q000517:prevention & control*; D011792:Quebec / Q000453:epidemiology; D018570:Risk Assessment / Q000379:methods
chemical_list: D018501:Antirheumatic Agents; D001688:Biological Products