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Do NSAID, COX-2, or Opioid Rxs Increase Non-Union Risk?

July 8, 2020

Written by Clay Smith

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Selective COX-2 inhibitors appear to increase risk for fracture non-union. Regular NSAIDs do not. Opioids may also increase non-union risk, although this association may have been confounded.

Why does this matter?
COX-2 is important in fracture healing. NSAIDs have some COX-1 and some COX-2 inhibition. Selective COX-2 inhibitors…well selectively inhibit only COX-2. Since both impact COX-2 production as part of the inflammatory response, might this increase the risk of non-union?

Breaking news…
Using a large insurance database over a period of almost 16 years (Optum, with >60 million members in the U.S.), authors looked at the risk on fracture non-union in patients exposed to COX-2 inhibitors or regular NSAIDs. Non-union requiring surgery was rare, 2,996 (0.9%) of 339,864 fractures. Exposure to a selective COX-2 inhibitor was associated with an 84% increase in the odds of non-union (OR 1.84, 95%CI 1.38 to 2.46); an opioid prescription increased odds 69% (OR 1.69, 1.53 to 1.86); regular NSAIDs were not associated with non-union (1.07, 0.93 to 1.23). Risk increase was similar when considering a non-union diagnosis vs the more stringent criterion of non-union requiring surgery. It is unknown if the association with filling an opioid prescription may have been confounded, as these patients had greater severity injuries.

Risk of Nonunion with Nonselective NSAIDs, COX-2 Inhibitors, and Opioids. J Bone Joint Surg Am. 2020 May 25. doi: 10.2106/JBJS.19.01415. [Epub ahead of print]

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What are your thoughts?