Effects of disease-modifying antirheumatic drugs on nonvertebral fracture risk in rheumatoid arthritis: a population-based cohort study

J Bone Miner Res. 2012 Apr;27(4):789-96. doi: 10.1002/jbmr.1489.


Several prior investigations demonstrate an improvement in bone mineral density associated with use of tumor necrosis factor inhibitors (TNFi). We compared the risk of osteoporotic fractures among patients with rheumatoid arthritis (RA) initiating a disease-modifying antirheumatic drug (DMARD). A population-based cohort study was conducted using health care utilization data (1996-2008) from a Canadian province and a U.S. commercial insurance plan. Patients with at least two RA diagnoses were identified, and follow-up began with the first prescription for a DMARD. Drug regimens were categorized into three mutually exclusive hierarchical groups: (1) TNFi with or without nonbiologic DMARDs (nbDMARD), (2) methotrexate (MTX) without a TNFi, or (3) other nbDMARD without a TNFi or MTX. Main outcomes were hospitalizations for fractures of the hip, wrist, humerus, or pelvis based on diagnoses and procedure codes. The study cohort consisted of 16,412 RA patients with 25,988 new treatment episodes: 5856 TNFi, 12,554 MTX, and 7578 other nbDMARD. The incidence rate per 1000 person-years for osteoporotic fracture were 5.11 [95% confidence interval (CI) 3.50-7.45] for TNFi, 5.35 (95% CI 4.08-7.02) for MTX, and 6.38 (95% CI 3.78-10.77) for other nbDMARD. After multivariable adjustment for osteoporosis and fracture-related risk factors, the risk of nonvertebral osteoporotic fracture was not different in either TNFi [hazard ratio (HR) 1.07, 95% CI 0.57-1.98] or MTX (HR 1.18, 95% CI 0.60-2.34) compared with nbDMARD. Among subjects diagnosed with RA, the adjusted risk of nonvertebral fracture was similar across persons starting a TNFi, MTX, or other nbDMARD.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antirheumatic Agents / pharmacology
  • Antirheumatic Agents / therapeutic use*
  • Bone Density / drug effects
  • Canada / epidemiology
  • Cohort Studies
  • Female
  • Fractures, Bone / complications*
  • Fractures, Bone / drug therapy*
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Osteoporotic Fractures / complications*
  • Osteoporotic Fractures / drug therapy
  • Osteoporotic Fractures / epidemiology*
  • Proportional Hazards Models
  • Risk Factors
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • United States / epidemiology


  • Antirheumatic Agents
  • Tumor Necrosis Factor-alpha