Certain Drugs Increase or Reduce Fracture Risk in Rheumatoid Arthritis

Study Authors: Gulsen Ozen, Sofia Pedro, et al.

It has been known that opioid use increases risk of fracture and osteoporosis in RA patients, and that to begin with, individuals with RA have twice the risk of fracture as the general population. Researchers therefore set out to find which other drugs elevate, and which reduce, risk of fractures in RA patients. They found that the following drugs elevated fracture risk, in addition to opioids:

  • SSRIs (vertebral and non-vertebral) and glucocorticoids.
  • Conversely, TNF inhibitors and statins reduced vertebral fracture risk.
  • PPIs and antidepressants other than SSRIs did not elevate fracture risk, according to this research.
  • For RA patients, chronic inflammation is a given, which alone raises fracture risk, as well as elevating the use of drugs including analgesics, antidepressants, and DMARDs to treat co-morbidities.

Regarding how pharmaceuticals elevate risk of fracture:

  • potential mechanisms by which opioids could increase fractures include raising the risk of falls and effects on bone metabolism, but that greatest risk during the first month of exposure suggests that fall risk is the more likely mechanism, the researchers noted.
  • In contrast, the elevated fracture risk associated with SSRIs increased with longer use, so bone metabolism effects may be involved.
  • The potential benefits of statins may relate to anabolic and anti-osteoclastic effects, and the protective influence of TNF inhibitors may arise from these agents' powerful anti-inflammatory effects.

Osteoporotic fractures are an important cause of both morbidity and mortality in RA, so the recognition of potentially modifiable risk factors, such as medications, is crucial. "We suggest a regular review of the necessity of the medications being used," Michaud and colleagues advised. "In the opioid epidemic era, to avoid fractures and other devastating consequences, opioid use should be minimized for pain management in RA," they concluded.

Reference: Annals of the Rheumatic Diseases 2019: DOI: 10.1136/annrheumdis-2019-215328