Abstract
The aim was to analyze whether non-steroidal anti-inflammatory drugs (NSAIDs) have an adverse effect on bone healing by evaluating all available human randomized controlled trials (RCTs) on this subject.
A systematic search of electronic databases (PubMed, MEDLINE, and Cross-References) was performed to identify RCTs comparing the occurrence of nonunion in patients who received NSAIDs to the control group. Risk of bias of the studies was assessed. Nonunion was the main outcome evaluated, however, regression analysis was used to estimate the relative risk comparing duration and type of NSAIDs.
Six RCTs (609 patients) were included. The risk of nonunion was higher in the patients given NSAIDs after the fracture (P-value= 0.0009, relative risk [RR] = 2.9, 95% confidence interval [CI] = 1.6 to 6.3). However, once the studies have been categorized to the duration of NSAIDs, those who received short period of NSAIDs (4 weeks) (P-value = 0.0002, RR = 4.1, CI = 2.1 to 8). Also, indomethacin agent has associated with high nonunion (P-value = 0.0001, RR = 3.9, CI = 2.3 to 13.9) compared to other NSAIDs which did not show a nonunion risk (P-value = 0.24, RR = 2.3, CI = 0.6 to 8.9).
Using NSAIDs for long period (> 4 weeks) after fracture is significantly associated with nonunion especially with indomethacin agent. However, short period of NSAIDs (< 2 weeks) did not show the adverse effects of nonunion. Overall, further studies are required to support our conclusion.
