SLR - February 2011 - Matthew Riordan
Reference: Dodwell, E.R., Latorre, J.G., Parisini, E., Zwettler, E., Chandra, D., Mulpuri, K., Snyder, B. (2110). NSAID Exposure and Risk of Nonunion: A Meta-Analysis of Case-Control and Cohort Studies. Calcified Tissue International, Vol 87, No. 3 193-202.
Scientific Literature Reviews
Reviewed by: Matthew Riordan, DPM, PGY-2
Residency Program: Cambridge Health Alliance
Podiatric Relevance:
It is well known that multimodal analgesia greatly reduces narcotic use in the postoperative period. Non-steroidal anti-inflammatories (NSAIDS) are particularly effective in reducing the need for postoperative narcotics; however, today there is great debate as to whether or not NSAIDs increase the risk of non-union in healing fractures. This study systematically reviews the current literature regarding the effects of NSAID exposure on bone healing.
Methods:
A comprehensive meta-analysis using Medline, Embase and Cochrane databases was performed pooling literature from 1966 to December 2008. Minimum follow-up of the included studies was 3 months for long bone fractures and one year for spinal fusions. The Newcastle-Ottawa scale was used to analyze the study quality and only studies of greater than 5 on the 9-point scale were considered for review. Metaregression was used to evaluate the risk of non-union as a function of the quality of the study, mean age of the study population, length of follow-up and smoking history.
Results:
One hundred and fifty-eight articles met the search criteria of which 11 studies were deemed eligible for inclusion in the meta-analysis. In those studies there were 2,067 patients were exposed to NSAIDs, of which, 150 went on to develop non-unions. Of the 9,984 patients that were not exposed to NSAIDS 151 developed non-unions. This data showed a statistically significant increase in risk of non-union with exposure to NSAIDs, however, there was also a significant association between the lower quality studies and increased risk of non-union. When only the highest quality studies were considered (Newcastle-Ottawa <7), there was no demonstrated risk of non-union.
Conclusion:
NSAIDs are an effective adjunct to postoperative pain control. Unfortunately, there is conflicting data with regards to their deleterious effect on bone healing. Furthermore, a large number of studies on this subject were recently retracted due to research fraud allegations and there are currently no published randomized controlled trials in human subjects.
There are several weaknesses of this meta-analysis beginning with the initial selection of articles that contained studies including long bone fractures and spinal fusions. The non-union rate in these areas is significantly different with a non-union rate of 1-6% in long bones and 10-15% in spine. As discussed earlier, there was a significant association between lower study quality and reported non-union rates. In addition, the included studies varied in NSAID type, dose and duration, as well as their definition of non-union. There was also significant potential for selection bias based on the retrospective nature of many of the included studies.
Despite the limitations of the meta-analysis, it is useful in quantifying the current literature on the topic. Based on the information gathered, there does appear to be an increased incidence of non-union with NSAID use in long bone fractures and no association in spinal fusions. There is currently no clear contraindication to NSAID use in patients with healing bone. There is an obvious need for randomized controlled trials to assist in clarifying this controversial issue.