Biological Disease-Modifying Antirheumatic Drugs and Osteoporotic Fracture Risk in Patients with Rheumatoid Arthritis: A Danish Cohort Study

Am J Med. 2022 Jul;135(7):879-888.e3. doi: 10.1016/j.amjmed.2022.01.017. Epub 2022 Feb 5.


Objectives: Clinical trials have shown a beneficial effect from biological disease-modifying antirheumatic drugs (bDMARDs) on hand or axial bone loss in patients with rheumatoid arthritis; however, it is unclear if this translates to a reduced fracture risk. We investigated the effect of bDMARDs on osteoporotic fracture risk compared to no biological treatment in rheumatoid arthritis.

Methods: A cohort of patients with rheumatoid arthritis aged 18+ from DANBIO was linked to population-based health registries in Denmark (2006-2016). Adopting a prevalent new-user design, we matched bDMARD users to bDMARD-naïve patients using time-conditional propensity scores. The risk of incident osteoporotic fractures (including hip, vertebrae, humerus, and forearm) was estimated among the matched patients by Cox proportional hazards models.

Results: Out of 24,678 patients with rheumatoid arthritis, 4265 bDMARD users were matched to the same number of bDMARD-naïve patients (mean age 56.2 years, 74% female). During follow-up, 229 osteoporotic fractures occurred among bDMARD users and 205 fractures among bDMARD-naïve patients (incidence rates 12.1 and 13.0 per 1000 person-years, respectively). The use of bDMARDs was not associated with a reduced risk of osteoporotic fractures among patients with rheumatoid arthritis (hazard ratio 0.97, 95% confidence interval 0.78-1.20), compared with no biological treatment. The risk estimates were similar for all osteoporotic fracture sites.

Conclusion: We found no independent beneficial effect from using bDMARDs on reducing the risk of osteoporotic fractures in patients with rheumatoid arthritis.

Keywords: Biological products; Disease-modifying antirheumatic drugs; Osteoporotic fractures; Rheumatoid arthritis.

MeSH terms

  • Antirheumatic Agents* / adverse effects
  • Arthritis, Rheumatoid* / complications
  • Arthritis, Rheumatoid* / drug therapy
  • Biological Products* / therapeutic use
  • Cohort Studies
  • Denmark / epidemiology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Osteoporotic Fractures* / epidemiology
  • Osteoporotic Fractures* / etiology
  • Osteoporotic Fractures* / prevention & control
  • Registries


  • Antirheumatic Agents
  • Biological Products