Why We Do What We Do: NSAIDs and Bone Healing

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A 79 year old male presents to your emergency department after having tripped and fallen on an outstretched hand. Patient did not hit his head or lose consciousness. Xray shows a slightly posteriorly angulated Colle’s fracture. Patient gets casted in the ER and is stable for discharge. How do we control this patient’s pain? Do we give opiates alone? Should we be giving NSAIDs?

A frequent question that is raised in the ER is how to control pain in such situations. The concern around giving NSAIDs to a fracture is a legitimate one. NSAIDs are effective at reducing acute pain and regional swelling and help us reduce the amount of Percocet perscriptions we are writing our patients. They also have a smaller side effect profile. They do what they do by a nonselective acetylation of the cyclooxygenase enzyme (COX). This enzyme is important in converting arachidonic acid to prostaglandinds and leukotrienes. Research has identified that some of these pro-inflammatory prostanoids, specifically generated by COX-2, are important for initiation of bone healing mechanisms and recruiting osteoblasts. Many in vitro studies have suggestions have supported the theory that disabling the COX enzyme will adversely affect bone healing.

A lot of studies have been done prospectively in animal models and have suggested that both selective and nonselective COX inhibitors delay primary fracture healing as well as increase nonunion rates. In these models, researchers have identified both timing of dosing (i.e. early in the healing process) and higher concentrated dosing associated with delayed fracture healing. Even as recent as this year a study was released in the Journal of Bone and Joint Surgery, describing the effect of Aspirin 325mg on bone healing in a rabbit ulnar osteotomy model. Conclusions of this study corroborate that NSAIDs delay bone healing.

Ultimately the question persists, do animal models translate effectively to human patients. Most of our evidence stems from retrospective studies. In 2005 a study was performed looking at elderly population with bone injuries and suggested that NSAID administration given within 90 days is significantly associated with nonunion. There are no large prospective studies looking at long term administration of NSAIDs and bone healing. Short-term administrations of certain NSAIDs including celecoxib, rofecoxib or low-dose toradol don’t translate into an increase in nonunion.
The theories supported by in vitro and animal studies support our hesitation giving NSAIDs to our fracture patients. The evidence in human studies is still weak and in time we will hopefully have clearer answers of the role of COX inhibition in human bone healing. This author’s humble opinion is steer away from NSAIDs unless only short term use for pain is being considered. What do you think in light of the evidence? And for those of you who don’t know the character at the top of the page is a comic-book character named Bone.

Krumis, AP et al. The Effect of Nonsteroidal Anti-inflammatory Drug Administration on Acute Phase Fracture-Healing: A Review, J Bone Joint Surg Am. 2012;94:815-23.
Busti AJ et al., Effects of perioperative anti-inflammatory and immunomodulating therapy on surgical wound healing. Pharmacotherapy 2005;25:1566-91.
Hernandez, RK et al., Patient-related risk factors for fracture-healing complications in the United Kingdom General Practice Research Database, Acta Orthopaedica 2012; 83(6):653-660.
Lack WD, et al., Effect of Aspirin on Bone Healing in a Rabbit Ulnar Osteotomy Model, J Bone Joint Surg Am. 2013;95:488-96.

Dr. Michael Meguerdichian

One Comment

  • alvarezzy

    in an academic program, it’s nice to raise this question to the orthopods. i give nsaids to my patients with fractures, especially kids who will have non-operative repair, especially after the blackbox warning for tylenol #3 in pediatric population. however, in a private/community practice, if the orthopod does not want nsaids, and you are referring the patient to them, probably not a fight you want to start.. unless you have other orthopods in line to call =)


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