Stronger Opioids No More Effective for Fractures Managed Surgically

close up of a group of white tablets with an out of focus prescription bottle in the background
This study found no evidence that stronger opioids were superior to milder opioids for subacute pain.

For patients with surgically managed orthopedic fractures, there was no evidence that strong opioid medication was superior to milder medications for subacute pain. These findings were published in JAMA Network Open.

Patients who underwent surgical treatment for ≥1 acute fracture between 2016 and 2017 at a major trauma hospital affiliated with the University of Sydney in Australia (N=120) were recruited for this study. Patients were randomized to receive 5 or 10 mg oxycodone hydrochloride (n=59) or 500 or 1000 mg acetaminophen and 8 or 16 mg codeine (n=61) 4 times per day for 2 weeks after release from hospital. Medications were titrated to the lower dose at week 3. On days 3, 7, 14, and 21, participants were contacted by telephone and asked about their pain.

The strong opioid and milder medication cohorts were 72.9% and 77.1% men, aged mean 36.0 (standard deviation [SD], 14.1) and 38.2 (SD, 13.5) years, BMI was 27.4 (SD, 6.4) and 29.0 (SD, 6) kg/m2, 20.3% and 23.0% had ≥1 comorbidity, 1.7% and 3.3% were recreational drug users, 84.8% and 90.2% had 1 fracture, and 50.8% and 60.7% had lower extremity fractures, respectively.

Prior to hospital discharge, mean pain on a numerical rating scale (NRS) was 4.2 (SD, 1.56) and worst pain was 6.5 (SD, 1.9).

Between days 1 and 7 after discharge, the group difference in pain was -0.50 (95% CI, -1.11 to 0.12; P =.11). The difference in pain between groups was also similar between days 1 to 21 (mean difference, -0.45 (95% CI, -1.06 to 0.16; P =.15).

Significant group differences were not observed between days 1-21 for daily adverse effects (P =.06), worst pain (P =.37), and mean daily tablet use (P =.69). The proportion of patients who returned to work on days 3 (P =.26), 7 (P >.99), 14 (P =.79), and 21 (P =.76) did not differ. No significant difference for global perceived effect on days 7 (P =.88), 14 (P =.69), or 21 (P =.29) were observed.

At the end of the study, 56.0% of the oxycodone group would not guess which treatment they had been assigned to, 30.5% incorrectly thought they were assigned to the milder cohort, and 13.5% correctly guessed their assignment. For the mild cohort, 34.5% correctly guessed their assignment and 26.2% were incorrect.

No significant differences in satisfaction were reported (P =.51).

The findings from this study may not be generalizable as it was a single-center study conducted in a region with a high level of socioeconomic disadvantage.

This study did not find evidence to support the use of strong opioids after surgical intervention for orthopedic fractures.


Jenkin DE, Naylor JM, Descallar H, Harris IA. Effectiveness of oxycodone hydrochloride (strong opioid) vs combination acetaminophen and codeine (mild opioid) for subacute pain after fractures managed surgically: a randomized clinical trial. JAMA Netw Open. 2021;4(11):e2134988. doi:10.1001/jamanetworkopen.2021.34988