NSAIDs and Bone Healing in Fractures
Short-term NSAID use (≤2 weeks) does not impair fracture healing in humans and can be safely used for acute pain management, though prolonged use should be avoided in patients at high risk for delayed union.
Evidence Quality and Recommendations
The concern about NSAIDs interfering with bone healing stems primarily from animal studies, but high-quality human clinical evidence does not support this fear for short-term use 1, 2.
Key Clinical Evidence
Pediatric fractures: A prospective, randomized, blinded study of 95 children with long bone fractures found no difference in healing time between ibuprofen users (mean 31 days) and acetaminophen controls (mean 40 days, p=0.76), with 100% healing achieved in both groups by 6 months 3.
Adult tibia fractures: A multicenter retrospective study of 372 patients with diaphyseal tibia fractures treated with intramedullary nailing showed no significant difference in healing time between NSAID users (180.5 days) and opioid users (185 days, p=0.64) 4.
Colles' fractures: A triple-blinded randomized controlled trial of 95 patients found no difference in bone mineral density, histomorphometric characteristics, or bone turnover markers between patients receiving ibuprofen (3 or 7 days) versus placebo 5.
Meta-Analysis Findings
A meta-analysis of 11 observational studies initially suggested increased nonunion risk (OR 3.0,95% CI 1.6-5.6), but when restricted to only high-quality studies (primarily spine fusion cases), no statistically significant association was found (OR 2.2,95% CI 0.8-6.3) 2. Lower-quality studies systematically overestimated the risk 2.
Clinical Practice Guidelines
Perioperative spine surgery: Current evidence indicates that short-term NSAID use (<2 weeks) is safe for spinal fusion, with nearly all studies after 2005 supporting this conclusion 6. There is no level 1 evidence from human studies linking short-term NSAID use to reduced fusion rates 6.
Trauma pain management: NSAIDs should be used with caution in elderly trauma patients due to potential adverse events (acute kidney injury, gastrointestinal complications), but the 2023 WSES guidelines note that acetaminophen is not inferior to NSAIDs for minor musculoskeletal trauma 6. When NSAIDs are used in elderly patients, co-prescribe a proton pump inhibitor and monitor for drug interactions with ACE inhibitors, diuretics, or antiplatelets 6.
Bone pain management: For cancer-related bone pain, NSAIDs combined with opioids may improve pain control, though their analgesic effects are modest 6.
Practical Algorithm for NSAID Use in Fractures
Safe to Use (Short-term ≤2 weeks):
- Acute fracture pain in children and adults 3, 4
- Long bone fractures treated operatively or non-operatively 3, 4
- Perioperative pain after spine fusion 6
- Distal radius fractures 5
Use with Caution:
- Elderly patients: Risk of renal injury and GI complications; always co-prescribe PPI 6
- Patients on anticoagulants/antiplatelets: 3-6 fold increased bleeding risk 7
- Preexisting renal disease: NSAIDs can cause volume-dependent renal failure 7
- Cardiovascular disease history: Increased risk of cardiac events, particularly in first week of use 6
Avoid or Consider Alternatives:
- High-risk nonunion patients: Multiple comorbidities, smoking, diabetes, poor nutrition 1
- Prolonged use >2 weeks: Animal data suggest dose and duration-dependent effects 1
- Perioperative hip fracture surgery in elderly: Not recommended per WSES guidelines 6
COX-2 Selective Inhibitors
COX-2 inhibitors (celecoxib) provide anti-inflammatory effects without increased bleeding or GI side effects 6. Meta-analyses show they reduce postoperative pain scores, opioid consumption, and nausea/vomiting when given preoperatively and continued postoperatively 6. However, they carry cardiovascular risks similar to non-selective NSAIDs 6.
Common Pitfalls
Overestimating risk: The theoretical concern from animal studies does not translate to clinically significant impairment in humans for short-term use 1, 2, 3, 4.
Avoiding all NSAIDs unnecessarily: This forces reliance on opioids, which carry significant risks of respiratory depression, over-sedation, nausea, and addiction, particularly in elderly patients 6.
Ignoring drug interactions: Combining NSAIDs with anticoagulants, ACE inhibitors, or diuretics significantly increases adverse event risk 6, 7.
Prolonged use without reassessment: While short-term use appears safe, effects beyond 2 weeks are less well-studied and should be avoided in high-risk patients 6, 1.