The efficacy and safety of celecoxib for postoperative pain in major orthopedic surgery: a systematic review and pairwise meta-analysis

Effective postoperative pain management is crucial for surgical recovery, yet opioid-based therapies carry significant risks of addiction and adverse effects. Celecoxib, a selective COX-2 inhibitor, has emerged as a promising non-opioid alternative within multimodal analgesic protocols. This systematic review and meta-analysis aimed to synthesize current evidence regarding the efficacy and safety of celecoxib specifically for major orthopedic surgeries. Following a PROSPERO-registered protocol, researchers searched major databases through 09th September 2025 for randomized controlled trials (RCTs) involving adults undergoing major orthopedic procedures. The primary outcome was postoperative pain intensity at 1, 3, 5, and 7 days. Data synthesis utilized standardized mean differences (SMD) and random-effects models. The GRADE assessment was applied to all the outcomes included. Among 643 works initially included, 16 RCTs involving 1,816 participants were initially included and 1,678 finished the follow-up. Celecoxib significantly reduced pain intensity at day 1 (SMD: -0.553; p = 0.02) and day 3 (SMD: -0.760; p = 0.02), though benefits were not statistically significant by day 7. Preoperative administration (pre-emptive analgesia) was more effective than postoperative dosing alone. In exploratory subgroup analyses, preoperative administration and patient age younger than 65 years showed statistically significant pain reductions within their respective strata; however, tests for subgroup interaction did not reach statistical significance ( p > 0.05). Celecoxib use resulted in a mean reduction of 5.268 mg in morphine consumption. High-certainty evidence indicated no increased risk of side effects, including nausea, gastrointestinal side effects, or somnolence. In conclusion, celecoxib is an effective and safe intervention for managing acute postoperative pain in major orthopaedic surgery. Its significant opioid-sparing effect and favorable safety profile support its use as a pre-emptive analgesic to optimize early recovery.