Date: January 22nd, 2021

Guest Skeptic: Dr. Steve Joseph. Steve completed his Sport Medicine fellowship training with the Fowler Kennedy Sport Medicine Clinic in 2017.  He served with the Canadian Forces as a Medical Officer and Flight Surgeon. Steve is currently an Assistant Professor in the Department of Family Medicine at Western University (London, Ontario) working at the Fowler Clinic and the Roth McFarlane Hand and Upper Limb Centre.

Reference: George et al. Risk of Nonunion with Nonselective NSAIDs, COX-2 Inhibitors, and Opioids. J Bone Joint Surg Am. 2020

Case: A healthy 55-year-old woman was out for a walk and had a FOOSH (fall on outstretched hand) of her dominant arm. The X-ray demonstrates a fracture of the distal radius that is in an acceptable position and does not require a reduction. You immobilize her in a below elbow splint which provides significant pain relief and refer her to the local orthopedic fracture clinic. Upon discharge she asks what she should take for pain because she read somewhere that anti-inflammatory drugs like ibuprofen can prevent bone healing. She currently takes thyroid replacement therapy and has no known drug allergies.

Background: There are conflicting studies about fracture healing and the use of non-steroidal anti-inflammatories (NSAIDs) in humans. It remains a controversial topic in the orthopaedic specialty.

When bones break, they usually heal with either surgical or non-surgical management. Sometimes the healing process can take longer than usual (delayed union), does not heal (non-union) or in poor alignment (malunion). Non-union is defined as “a failure of the fracture-healing process” and occurs in up to 1 in 10 fractures.

Several risk factors have been associated with increased risk of delayed or non-union. These factors include: Use of tobacco products, older age, severe anemia, alcohol intake, diabetes, low vitamin D levels, hypothyroidism, poor nutrition, infection, open fracture and certain medications (ex. steroids). The top risk factors for non-union according to a study by Santolini et al were open method of fracture reduction, open fracture, presence of post-surgical fracture gap, smoking, infection, wedge or comminuted types of fracture, high degree of initial fracture displacement, lack of adequate mechanical stability provided by the implant used, fracture location in the poor zone of vascularity of the affected bone, and a fractured tibia [1].

One class of medication that has been implicated in negatively impacting bone healing is NSAIDs. Non-selective NSAIDs block cyclooxygenase (COX)-1 and 2 while selective NSAIDs only inhibit COX-2. There have been multiple studies investigating this issue with mixed results.

Clinical Question: Is there increased risk for fracture non-union with certain classes of NSAIDs?

Reference: George et al. Risk of Nonunion with Nonselective NSAIDs, COX-2 Inhibitors, and Opioids. J Bone Joint Surg Am. 2020

* Population: Adults (18 years and older) inpatient or outpatients with a diagnosis of certain long bone fractures (neck of femur/tibia/fibula/tibia and fibula/radius/ulna/humerus/clavicle) based on ICD-9 codes.

* Excluded: Patients less than 18 years of age, multiple fractures, metastatic disease, history of malunion fracture in the year prior or within 90 days

* Exposure: Filled prescription for a non-selective NSAIDs, selective COX-2 inhibitor and/or opioid within 30 days of the fracture

* Comparison: Not filling a prescription for a non-selective NSAIDs, selective COX-2 inhibitor and/or opioid within 30 days of the fracture

* Outcomes:

* Primary Outcome: Diagnosis of non-union within the 91 to 365 days post fracture. This was based on two definitions.