In this study, we found six predictors of non-union after surgery for limb fractures: osteoporosis, open fracture, NSAIDs use, delayed weight bearing, failed internal fixation, and infection. Other patient- and injury-related factors, such as age, sex, BMI, obesity, smoking, alcohol, hypertension, diabetes, closed fracture, and multiple fractures, were not significant risk factors.
Without controlling for potential confounding factors, it is not clear whether age and sex itself are risk factors for bone non-union. Although the number of patients included in this study is relatively large, it is not sufficient to control the confounding effect of age and sex. Some studies have reported that age and sex are positively correlated with the risk of non-union [17, 18], while other reports show that there is no significant correlation [19, 20]. It is worth noting that the average age of the population in this study is only approximately 40 years old, and the results may not apply to older patients. This may also explain why age-related factors such as obesity, smoking, alcohol, hypertension, and diabetes have not been identified as statistically significant risk factors in this study, despite being suggested as possible causes of bone non-union in previous studies [21–25]. In addition, one study positively found a significant correlation between osteoporosis and the risk of non-union , which is in line with the present study’s findings. However, another case-control study evaluated 1498 patients and failed to find such an association .
In our study, no significant correlation was found between the presence of multiple fractures and non-union. On the contrary, a previous study showed that non-union seems to be associated with multiple fractures . This discrepancy may be related to the small proportion of non-union (n = 15, 6.7%) in patients with multiple fractures in our study; further studies with larger samples are needed to provide a more definitive understanding of the role of multiple fractures. However, a significant proportion of non-union cases occurred in patients with open fractures (n = 76, 34.1%), and the multiple regression analysis showed that patients with open fractures have a greater risk of non-union, which was consistent with the results of a previous study . Compared with closed fractures, open fractures are associated with relatively greater trauma, more serious destruction of soft tissue blood supply, higher probability of infection, and decreased blood supply, thus affecting bone healing . This also explains that patients with open fractures have a relatively high rate of healing disturbances.
Basic studies have shown that NSAIDs use affects bone healing, mainly due to their inhibiting effect on cyclooxygenase-2, which delays fracture healing . A recent retrospective clinical study of 1900 patients with long bone fractures showed that the postoperative use of NSAIDs doubled the risk of healing complications . Moreover, Giannoudis et al. have demonstrated that there is a highly significant relationship between NSAIDs use and bone non-union (P < 0.001) . Our findings suggest that the NSAIDs use after surgery for limb fractures is associated with a 2.04-fold higher odds ratio of non-union, which is in line with the results of previous studies.
It is crucial to start weight bearing after a fracture since it helps maintain bone and muscle mass and helps restore the performance of activities of daily living. Additionally, weight bearing promotes bone healing through a process called mechanical transduction . Recently, a study demonstrated the safety of early weight bearing after fracture surgery . We identified a significant association (P < 0.001) between delayed weight bearing after surgery and the development of non-union, which is consistent with the results of the study by Westgeest et al. . Furthermore, delayed weight bearing was identified as an independent risk factor for the development of non-union in the multivariate analysis. This finding may be explained by a relationship between weight bearing and healing outcomes in the reverse direction. That is, bone non-union may cause more pain, resulting in delayed weight bearing, rather than delayed weight bearing causing non-union . Additionally, internal fixation failure is often considered as a reason to postpone the initial weight bearing. In this study, internal fixation failure (n = 44, 19.7%) accounted for a large proportion of bone non-union cases, which indicates that there is some association between failed internal fixation and delayed weight bearing. Indeed, our results showed that failed internal fixation (OR = 5.93, 95% CI: 2.85 to 12.36) significantly increases the risk of non-union.
Different opinions have been put forward on whether there is a connection between infection and non-union. Most scholars believe that infection does not increase the risk of non-union [38–40]. However, a prospective cohort study evaluated 736 patients and showed that infection was significantly associated with non-union . The results of our analysis show that infection is an independent risk factor for non-union, with a 6.77-fold higher risk of non-union in patients with infection. There was also a significant correlation between infection and non-union. This may be due to the increased fracture end necrosis and vascular embolism, giving rise to poor local bone blood supply, so that the formation of bone is disturbed and healing is impaired, ultimately resulting in bone non-union .
Despite these findings, this study has some limitations. First, although we designed a 1:2 matched case-control study to try to minimise the impact of the small sample size, our sample may not fully represent all postoperative patients with limb fractures and may also not be large enough to make our regression analysis conclusive. Second, multiple surgeons were involved in this retrospective study, each with a slightly different non-union definition and treatment. Finally, most patients in this study were middle-aged; thus, it is difficult to apply these findings to older patients. Therefore, further research in a wider age range is needed.