Rheumatoid arthritis: opioids, selective serotonin reuptake inhibitors and glucocorticoids increase fracture risk

  • Ozen G & al.
  • Ann Rheum Dis
  • 15 May 2019

  • curated by Sarfaroj Khan
  • UK Clinical Digest
Access to the full content of this site is available only to registered healthcare professionals. Access to the full content of this site is available only to registered healthcare professionals.


  • Opioids, selective serotonin reuptake inhibitors (SSRIs) and glucocorticoids are associated with increased risk for vertebral and non-vertebral fracture in patients with rheumatoid arthritis (RA).
  • Statins and tumour necrosis factor-α inhibitors (TNFi) are linked to decreased risk for vertebral fracture.

Why this matters

  • Opioid use, which is still frequent in RA should be minimised to avoid fracture risk and other consequences of opioids. Regular review of medications in these patients may help deprescription of unnecessary and potentially high-risk treatments.
  • Given the underuse of statins for cardiovascular disease in RA, the protective association against vertebral fractures may be encouraging for statin prescriptions in patients with RA.

Study design

  • 11,412 patients with RA who participated in the FORWARD study were evaluated for osteoporosis-related site fractures (vertebra, hip, forearm, and humerus).
  • Disease-modifying antirheumatic drug (DMARD) exposure was assessed in 4 mutually exclusive groups: methotrexate monotherapy (reference), TNFi, non-TNFi biologics and other synthetic DMARDs.
  • Primary outcome: incident fractures.
  • Secondary outcomes: vertebral and non-vertebral fractures.
  • Funding: None.

Key results

  • During 55,482 patient-years (median interquartile range [IQR], 3.0 (1.5-6.0) years) follow-up, 914 first-time fractures were reported (incidence rate, 16.5 [95% CI, 15.4-17.6] per 1000 patient-years).
  • After adjustment for confounders, risk for fracture was significantly higher with:
    • glucocorticoids dose
    • opioids; weak (HR, 1.37; 95% CI, 1.18-1.59) and strong (HR, 1.53; 95% CI, 1.24-1.88) , and
    • SSRIs (HR, 1.37; 95% CI, 1.15-1.63).
  • Fracture risk was increased with opioids use within 1 month (HR, 1.66; 95% CI, 1.36-2.04) and with SSRIs use for >3 months (HR, 1.25; 95% CI, 1.01-1.55).
  • Statins (HR, 0.77; 95% CI, 0.62-0.96) and TNFi (HR, 0.72; 95% CI, 0.54-0.97) were associated with lower risk for vertebral fracture.
  • Proton pump inhibitors and other psychotropic medications were not associated with increased fracture risk.


  • Patients were not randomly assigned to medications.
  • Risk of residual confounding.