Tramadol Linked to Lower Mortality and Fracture Risk Than Hydrocodone or Oxycodone in Osteoarthritis

Among adults aged 50 years or older with osteoarthritis (OA) who started an opioid, tramadol initiation was associated with lower risks of death and fracture than hydrocodone or oxycodone and with risks similar to those with codeine, according to a retrospective cohort study published online in Arthritis & Rheumatology.

Tramadol is commonly used to manage pain in patients with OA, but its comparative safety in this population remains largely unknown, wrote the investigators from Brigham and Women’s Hospital and Harvard Medical School. They compared all-cause mortality and fracture risk among patients initiating tramadol, codeine, hydrocodone, or oxycodone.

Using the Optum Clinformatics Data Mart (2005-2021), the investigators identified 1,057,635 patients (mean age, 69.1 years; 62.5% female), of whom 294,760 initiated tramadol, 97,048 codeine, 474,733 hydrocodone, and 191,094 oxycodone. Propensity score weighting was used to balance baseline characteristics. During follow-up, 9,988 deaths and 10,455 fractures occurred. Tramadol was associated with a lower risk of death than oxycodone (hazard ratio, 0.40; 95% CI, 0.34-0.47) and hydrocodone (hazard ratio, 0.81; 95% CI, 0.70-0.93).

Tramadol initiation was also associated with lower fracture risk than hydrocodone or oxycodone. Compared with codeine, the investigators reported similar risks of both death and fracture; the confidence intervals for these comparisons included the possibility of no difference.

The authors concluded that the findings suggest that tramadol may be a comparatively favorable option when opioid therapy is necessary, although its longer-term comparative safety remains uncertain. Because the study used a retrospective cohort design, the results reflect associations and do not establish that the choice of opioid caused the differences in risk.

Source: Sreedharas SK, Bea S, Huybrechts KF, et al. Comparative risks of mortality and fractures in patients with osteoarthritis initiating tramadol versus other opioids. Arthritis Rheumatol. Published online October 27, 2026. doi:10.1002/art.70383