The overall age distribution of patients with humeral shaft fracture was a bimodal pattern, with a small peak at 21–30 years old and a large peak at 71–80 years old 16. The main groups were young people suffering from high-energy trauma and old people suffering from low-energy trauma [4]. Entezari et al. found in the correlation research that distal-third humeral shaft fractures (p < 0.001, OR 6.3), high-energy trauma (p = 0. 049, OR 1.7), open fracture (p = 0. 048, OR 2.1) and concomitant vascular injury (p < 0.001, OR 26.9) were independent predictive factors, which were easy to lead to primary nerve injury [6].
Peripheral nerve injury is one of the common complications of humeral shaft fracture in the early stage. A prospective study by James et al. on more than 5,700 patients with multiple injuries suggested that radial nerve injury was the most common peripheral nerve injury, and 9.5% of humeral fractures were complicated with radial nerve injury17. Niver reviewed literatures and found that the rate of humeral shaft fractures associated with radial nerve injury was about 2–17% 10,18–20. Shao et al found in their retrospective study that the rate of humeral shaft fracture complicated with radial nerve injury was 11.8% (532/4517), and the middle and distal humeral shaft fractures were more likely to damage radial nerve 21. However, Ljungquist et al. mentioned that the rate of radial nerve injury caused by humeral shaft fracture was 22% 22, and Streufert et al. summarized the case data of two centers and found that the incidence of radial nerve injury was 18.4% (48/261) 23. Entezari et al. reported that the incidence of humeral shaft fracture complicated with nerve injury was about 25.5% (96/376), among which radial nerve injury accounted for about 94%, and the iatrogenic nerve injury incidence of humeral shaft fracture was 4.6% (7/154), all of which involved radial nerve6. In our study, the total rate of iatrogenic radial nerve injury caused by humeral shaft fracture was 6.16% (382/6205), and there was no significant statistical difference with the former (p > 0.05).
1. Comparison of iatrogenic radial nerve injury with different implants (bone plate and intramedullary nail)
The iatrogenic injury rates of the radial nerve caused by different treatment methods are different. For example, it has been reported that the iatrogenic injury rate of radial nerve of bone plate was 6.5%-12.0%, and that of intramedullary nails was 2.7-5.0% 4,24,25. This is similar to our statistical results, bone plate of 6.82% (313/4589), intramedullary nail of 2.58% (23/893). Amer et al. included three pieces of literatures in their meta-analysis study, and the results showed that for humeral shaft fracture (OTA/AO 12), plate (10.8%, 12/111) was more likely to cause iatrogenic radial nerve injury than intramedullary nail (0%, 0/104) (p = 0.0004 < 0.05) 8. However, Streufert et al. reported that the two-center study from 2008 to 2016 suggested that the iatrogenic radial nerve injury rate of the plate was 15.6% (10/64) in the middle humeral shaft and 15% (16/107) in the distal humeral shaft 23, which may be related to the diagnosis and treatment level of medical centers.
Ouyang et al. conducted a meta-analysis on 10 randomized controlled trials (RCT) and 439 cases and found that compared with intramedullary nail, bone plate avoided the risk of postoperative acromion impingement and limited shoulder joint movement, but there was no significant difference in iatrogenic radial nerve injury (p = 0.28 > 0.05) 26. Kurup et al. Reviewed five low-quality (unstratified) randomized trials, involving 260 participants, and reached the same conclusion as Ouyang et al. 27.
We included 3 articles about nonunion, involving 1 article about intramedullary nails and 3 articles about bone plates. Martínez et al. studied the treatment of middle and upper 2/3 of humeral shaft nonunion and found that the rate of iatrogenic radial nerve injury in non-reamed intramedullary nail and bone graft group was lower than that in open reduction and plate internal fixation group (0%, 0/24 VS. 11.54%, 3/26) 28. However, Singh et al. studied humeral shaft nonunion and found that there was no difference between intramedullary nail and plate internal fixation by posterior approach in nonunion healing time, joint function and iatrogenic radial nerve injury rate (0%, 0/20 VS. 10%, 2/20) 29. Koh et al. studied 379 cases of humeral shaft nonunion in 18 trauma centers, and found that there was no difference among anterolateral, lateral and posterior approaches (triceps-reflecting and triceps-splitting) approach, and fracture location (middle humerus) was the only related factor of radial nerve injury (p = 0. 02) 30. Olarte et al. found that radial nerve transposition was an effective auxiliary means for internal fixation of humeral shaft fracture, which was suitable for high-risk nonunion patients 31. A retrospective study of 19 patients by Chamseddine et al. found that medial transposition of the radial nerve was a safe and reliable method for patients who needed to take out internal fixation and nonunion 32.
Zalavras et al. provided a protocol for the treatment of nonunion of humeral shaft fracture and reported that 41 cases of nonunion were healed within 17 years without iatrogenic radial nerve injury; the protocol was also applicable to patients with long-term nonunion caused by complications 33.
2. Comparison of iatrogenic radial nerve injury by different surgical approaches (excluding MIPO)
Surgical approaches for humeral fractures included deltopectoral approach 34, anteromedial approach 12,13, anterolateral approach, lateral approach and posterior approach. The posterior approach included triceps-reflecting approach (Bryan-Morrey) 35, modified triceps-reflecting approach (Gerwin/Hotchkiss/Weiland)36, triceps-reflecting anconeus pedicle approach (TRAP)37, triceps-on approach/paratricipital approach (Alonso-Llames), triceps-splitting approach, the chevron olecranon V osteotomy, and tongue-shaped flap approach, etc.
Surgical approaches for humeral shaft fractures mainly included anterolateral, lateral and posterior approaches, and occasionally deltopectoral approach 34. Anteromedial approach was only seen in two pieces of literatures for MIPO treatment of humeral shaft fractures 12,13.
A retrospective study of 6 hospitals by Claessen et al. found that the rate of iatrogenic radial nerve injury caused by humeral shaft fracture was 7% (18/259); the surgical approach was related to iatrogenic radial nerve injury (p < 0.034), which was the only related factor (OR = 6.4 > 1); the incidence of iatrogenic radial nerve injury was 4% (7/165) in the anterolateral approach, 22% (2/9) in the lateral approach, and 11% (9/85) in the posterior approach 7. In our results, The rate of iatrogenic radial nerve injury in humeral shaft fracture was 6.16% (382/6205), which was similar to the results of Claessen (anterolateral: 5.65%, 111/1963; Posterior: 9.55%, 119/1246; p > 0.05); while the rate of radial nerve injury in lateral approach was 13.54% (26/192), which was lower than that of Claessen (22%, 2/9), but there was no statistical difference (p > 0.05). Different from the former, in our study, there were statistical differences between anterolateral approach and lateral approach, and between anterolateral approach and posterior approach in the rate of iatrogenic radial nerve injury (p > 0.05).
Multiple regression analysis by Shoji et al. showed that iatrogenic radial nerve injury had nothing to do with surgical approach and timing, but it was related to distal humeral fracture (AO/OTA 12A/B/C) and secondary or multiple operations due to a previous fracture, which was an independent risk factor 38.
Streufert et al. analyzed the case data of two centers and found that there was no difference in iatrogenic radial nerve injury rate among the three approaches: which were anterior/anterolateral approach (6/84), triceps lifting approach (14/78) and triceps-splitting approach (6/51) (p = 0.11) 23. A meta-analysis conducted by Shon et al. on 1303 cases in 9 studies showed that the rate of iatrogenic radial nerve injury through posterior approach was significantly higher than that through anterolateral approach (13.88%, 69/497 VS. 5.16%, 35/687) (OR 2.72; 95% CI, 1.70–4.35; p < 0.0001) 39. There was no significant difference between triceps-reflecting (3.9%, 2/51) and triceps-splitting (7.96%, 25/314) (p > 0.05), but there was a significant difference between posterior approach and anterolateral approach (7.4%, 119/1246 VS. 5.65%, 111/1963 p < 0.01). The main reason may be that the former had a small sample size and needed further specific study.
3. Comparison between open reduction and internal fixation (plate and intramedullary nail) and MIPO in iatrogenic radial nerve injury
A review by Tetsworth et al. suggested that MIPO had a lower rate of iatrogenic radial nerve injury 40. A meta-analysis of two randomized controlled trials and three non-randomized controlled trials by Yu et al. found that the rate of iatrogenic radial nerve injury in patients with MIPO was lower than that of traditional open reduction and internal fixation (p = 0. 006) 41. A meta-analysis by Hu et al. included 391 patients and 8 studies, involving 4 randomized controlled trials (RCTs), 2 prospective cohort trials and 2 retrospective cohort trials 42. It was also found that the iatrogenic radial nerve injury rate in the MIPO group was lower than that in open reduction and internal fixation, and the adjacent joint function score of MIPO was higher than that of intramedullary nail (IMN) (p < 0.05). Zhao et al. obtained the same results in a network meta-analysis of 16 randomized controlled trials (OR, 11.09; 95% CI, 1.80-124.20) 43. However, they also found that the incidence of acromion impingement in the intramedullary nail group was higher than that in the open reduction and plate internal fixation group (OR, 0.13; 95% CI, 0.03–0.37) and MIPO group (OR, 0.08; 95% CI, 0.00-0.69). There were no differences between Intramedullary nails, open reduction and plate internal fixation, and MIPO in delayed union, nonunion and infection of humeral fractures 43.
Our results showed that the rate of iatrogenic radial nerve injury in MIPO was lower than that in open reduction and internal fixation (2.70%, 12/444 vs 7.26%, 301/4145) (p < 0.05), which was consistent with the mentioned literatures.
4. Comparison of iatrogenic radial nerve injury caused by MIPO through different surgical approaches
At present, the main surgical approaches for the treatment of humeral shaft fractures by MIPO are anterolateral or posterior. However, Yang et al. found that medial MIPO was a safe surgical method for extra-articular fractures of the middle and distal humerus (0%, 0/12) 12. A single-center retrospective study by Liu et al. found that the radial nerve injury rate of anteromedial MIPO was low (0%, 0/21). The median nerve, ulnar nerve and brachial artery were protected by brachial muscle through the subbrachial tunnel without injury 13.
The results of this study showed that there was no significant difference among anterolateral MIPO, anteromedial MIPO and posterior MIPO in the rate of iatrogenic radial nerve injury (p > 0.05).
5. Comparison of iatrogenic radial nerve injury caused by an intramedullary nail through different approaches
There are two methods of intramedullary nailing for humeral shaft fracture: anterograde nail and retrograde nail. In this review, we found that there was no statistical difference in the incidence of iatrogenic radial nerve injury between anterograde and retrograde nailing (p > 0.05). Li et al. also found in their retrospective study that there was no significant difference in iatrogenic radial nerve injury rate between anterograde and retrograde intramedullary nailing 44.
6. The crawling regeneration distance of nerve fibers in radial nerve defect
Iatrogenic radial nerve injury includes continuation and discontinuation. In the latter, nerve defects often occur during secondary exploration, accompanied by permanent loss of sensory and motor function. However, in this study, a 14-year-old male child was observed, with a 4cm distance between the two nerve stumps, without an obvious continuous nerve bundle between the two nerve stumps, which suggested that the proximal nerve fibers crawled into the distal nerve stump through scar tissue and recovered part of the wrist extensor muscle strength. This case indicated that the regeneration ability of radial nerve was very strong, especially in children and adolescents. If the possibility of iatrogenic radial nerve injury is found, it should be actively explored and repaired.
7. Selection and optimization of implants
Wang et al. found that pre-contouring plates on 3D-printed fracture models can better help young doctors complete operations 45. For transverse fractures, 6-hole or 7-hole plates are generally used. However, clinically, most fractures are short oblique or long oblique fractures, even comminuted fractures. Therefore, 8–10 hole plates are often used in clinics. Taking a 10-hole plate as an example, the anatomical study of Chirattikalwong et al. on 56 humerus found that when a 4.5 mm 10-hole compression plate was used for fixation of the middle humeral shaft fracture through an anterolateral approach, the radial nerve would be damaged by the second to sixth holes, and the fourth hole and the fifth hole had the highest rate of injuries 46.
The anatomical study of Chuaychosakoon et al. on 18 upper limbs also held that when the middle humeral shaft fracture was fixed with a 4.5mm 10 holes compression plate through an anterolateral approach, the radial nerve and/or deep brachial artery would be damaged by the second to fifth holes, while the fourth and fifth holes were most likely to damage them, with the injury ratios of 100% and 66.7% respectively. The relative ratio of the distance between the fourth hole and the lateral epicondyle of the humerus to the length of the humerus was 0.56. The author suggested that a single-layer cortical screw should be used at the fourth hole 47.
An anatomical study by Noger et al. found that when distal interlocking fixation was performed with non-reamed intramedullary nails through an anterograde approach, the medial and lateral locking nails in the middle easily damaged the radial nerve, median nerve, ulnar nerve and brachial artery. The author believed that using the two anteroposterior screws was safe. If you want to improve the locking stability, it is recommended to complete the internal and external locking of the middle screw holes under direct vision 48. A retrospective study by Helm et al. found that anterograde intramedullary nail combined with cerclage can reduce the incidence of nonunion (2.6%, 2/78) without increasing the incidence of iatrogenic radial nerve injury (4.59%, 5/109) 49.
8. Conclusion
During humeral shaft fracture operation, the incidence of iatrogenic radial nerve injury was 6.82% in bone plate and 2.58% in intramedullary nails, respectively. Compared with lateral and posterior approaches, the anterolateral surgical approach had a lower incidence of radial nerve injury. The rate of iatrogenic radial nerve injury in MIPO was lower than that in open reduction and internal fixation. There was no difference in the incidence of iatrogenic radial nerve injury between anterograde and retrograde intramedullary nailing. In the human body, regenerated radial nerve fibers can span a 4cm nerve defect area.