Do Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) affect fracture healing?

From the Guidelines

NSAIDs should be avoided during fracture healing, especially in the first 1-2 weeks after injury, due to their potential to impair bone formation and delay healing. The use of NSAIDs can inhibit cyclooxygenase enzymes, which produce prostaglandins necessary for normal bone healing and remodeling, potentially leading to delayed callus formation, reduced bone mineralization, and increased risk of nonunion or delayed union, particularly in high-risk fractures like those of the scaphoid, fifth metatarsal, or tibia 1.

If pain control is needed, acetaminophen (up to 3000mg daily in divided doses) should be used as first-line therapy, as it is effective for pain relief without significantly impairing bone healing 1. For more severe pain, short-term opioids may be considered rather than NSAIDs, as they do not have the same negative effects on bone healing.

If NSAIDs must be used, the lowest effective dose for the shortest duration possible should be chosen, with ibuprofen (up to 400mg three times daily) or naproxen (up to 500mg twice daily) being reasonable options 2. However, it is essential to weigh the benefits of NSAID use against the potential risks, particularly in patients with additional risk factors for impaired healing, such as smoking, diabetes, osteoporosis, or advanced age.

In such cases, consider supplementing with vitamin D (1000-2000 IU daily) and calcium (1000-1200mg daily) to support bone health during the healing process. The most recent guidelines recommend a multimodal analgesic approach, including acetaminophen, gabapentinoids, and NSAIDs, for managing acute trauma pain in the elderly, with a strong emphasis on minimizing NSAID use and carefully evaluating the risks and benefits 1.

Key considerations for NSAID use in fracture healing include:

• Avoiding NSAIDs in the first 1-2 weeks after injury
• Using acetaminophen as first-line therapy for pain control
• Choosing the lowest effective dose and shortest duration of NSAID use if necessary
• Considering supplementation with vitamin D and calcium to support bone health
• Carefully evaluating the risks and benefits of NSAID use, particularly in patients with additional risk factors for impaired healing.

From the Research

NSAIDs and Fracture Healing

• The use of non-steroidal anti-inflammatory drugs (NSAIDs) in patients with traumatic fractures has been studied, and the results suggest that NSAIDs can reduce post-trauma pain and the need for opioids, but may have a small effect on non-union 3.
• The overall incidence of non-union in patients receiving NSAIDs compared with patients not receiving NSAIDs was 2.99% and 2.19% (p=0.04), respectively 3.
• Animal studies suggest that NSAIDs, which inhibit COX-2, can impair fracture healing due to the inhibition of the endochondral ossification pathway, and that the effects of COX-2 inhibitors are dependent on the timing, duration, and dose 4.
• Clinicians are advised to consider only short-term administration of COX-2 inhibitors or other drugs in the pain management of patients who are in the phase of fracture or other bone defect healing 4.
• NSAIDs are recommended as first-line treatment options for most patients with acute mild to moderate pain, but should be used with caution in patients with a history of gastrointestinal bleeding, cardiovascular disease, or chronic renal disease 5.

Risks and Benefits

• The use of NSAIDs in patients with traumatic fractures appears to have a small effect on non-union, but the benefit of reducing post-trauma pain and the need for opioids may outweigh the risks 3.
• COX-2 inhibitors should be considered a potential risk factor for fracture healing, and therefore should be avoided in patients at risk for delayed fracture healing 4.
• The combination of opioids and NSAIDs may be effective for acute pain management, but the use of opioids should be minimized due to the risk of addiction and overdose 6.

Clinical Guidelines

• Clinicians should tailor pharmacologic management of acute pain to each patient, including a review of treatment expectations and a plan for the time course of prescriptions 5.
• Topical NSAIDs are recommended for non-low back, musculoskeletal injuries, and acetaminophen is well tolerated, but lower doses should be used in patients with advanced hepatic disease, malnutrition, or severe alcohol use disorder 5.
• The use of opioids for acute pain management should be limited to short-term use under close clinical supervision, and combination therapy or nonopioid therapy may be preferred 6.