Background
Humeral shaft fractures account for 1–3% of all fractures [
1]. The incidence rate is 14.5 per 100,000 persons per year with a gradually increasing age-specific incidence from the fifth decade, reaching almost 60/100,000 per year in the ninth decade [
1].
Last decade, the optimal treatment for humeral shaft fractures was subject to debate. A recent meta-analysis shows that satisfactory results can be achieved with both nonoperative and operative management [
2]. The meta-analysis of data from randomized controlled trials (RCTs) in their review showed no statistically significant differences in favor of either one of the treatment options. Operative and nonoperative treatment each have their individual advantages and disadvantages. Surgical treatment is mostly performed using intramedullary nailing or plating, and the mostly used nonoperative treatment is immobilization with a functional (Sarmiento) brace or a cast [
3]. Fracture fixation allows for early mobilization, and is aimed to achieve earlier functional recovery. A disadvantage is the risk of surgical complications [
4]. Nonoperative treatment is aimed to achieve secondary bone healing by temporary immobilization of the arm. This initially results in functional impairment and may delay functional recovery. Moreover, the indirect fracture stabilization and risk of inadequate fracture alignment may increase the risk of malunion and nonunion [
5,
6]. Nonunion occurs in up to 10% of patients treated operatively and in up to 23% of patients treated nonoperatively [
2,
5,
6]. A complication that may occur after a humeral shaft fracture is radial nerve palsy. A systematic review reported an average radial nerve palsy rate at presentation of 11.8% in 4517 patients [
7]. The reported rate of radial nerve palsy due to surgery was 3.5% [
2]
.
The finding that the rate of surgical treatment was approximately 50% across all AO fracture subtypes indicates that consensus on the best treatment strategy for humeral shaft fractures was lacking at the time the study was designed [
8]. Lack of confirmative evidence about the best treatment strategy was also concluded in a Cochrane review [
9]. A survey among members of the British Elbow and Shoulder Society in 2021 concluded that the management preference for humeral shaft fractures among surgeons is highly variable, and that this may be partly attributed to the sparsity of high-quality evidence. They proposed that well-designed prospective cohort studies or randomized trials may guide further management of these injuries [
10]. The current study was designed to provide such high-quality evidence. We hypothesized that operative treatment would result in earlier functional recovery.
The primary objective of this study was to examine the effect of operative versus nonoperative treatment on the Disabilities of the Arm, Shoulder, and Hand (DASH) score, reflecting functional outcome and pain of the upper extremity, in adult patients who sustained a humeral shaft fracture. Secondary aims were to examine the effect of treatment on functional outcome (Constant–Murley) score, level of pain, range of motion of the shoulder and elbow joint, occurrence of complications with associated interventions, health-related quality of life, and the time to resumption of work and activities of daily living in these patients.
Discussion
Data from the current multicenter prospective study demonstrate that adult patients with a closed humeral shaft fracture AO type 12A or 12B treated operatively have a better outcome until six months than patients treated nonoperatively in terms of a lower DASH score, higher Constant–Murley score, improved shoulder and elbow ROM, and a higher health-related quality of life (EQ-5D US). In addition, the operated group had fewer complications and surgical re-interventions. Given the multicenter design, the findings of this study can be generalized and therefore will apply to all different levels of trauma centers.
The statistically significant difference in DASH score in the first six months after trauma of 8.8 points or more in favor of the operative group is in line with previous RCTs which show a mean difference of 18.0 and 6.0 points at six months [
23,
24]. In addition, the FISH trial also shows superior DASH scores until six month follow-up [
25]. The differences are larger than the minimally important change for the DASH (6.7 points) in the study population, confirming that our findings are statistically as well as clinically significant [
20]. Quick-DASH correlates highly with function and patient satisfaction, and is considered a suitable tool for evaluating adult humeral shaft outcomes [
26].
Similar as the DASH, the Constant–Murley score also showed superior upper extremity function in the operative group until six months after trauma. This was also shown in the FISH trial [
25], however, another RCT by Matsunaga et al
. found no significant difference in score during a 12 month follow-up period [
24]. It is not clear if this lack of difference can be attributed to a lower mean age, lower proportion of females, and inclusion of 12% of patients with an AO type 12C fractures in the nonoperative group in their study.
With regards to complications, both the current data and a meta-analysis show that pain, infection, and radial nerve palsy are no contributing factors in the decision-making for humeral shaft fractures [
2]. Both operatively and nonoperatively treated patients in the current study reported a similar level and decrease of pain during the 12 month follow-up. Similar findings have previously also been reported [
24]. Rämö et al
., on the other hand, reported slightly, yet statistically significant, less pain in the operative group until six weeks after trauma, but the difference in pain was less than the threshold for clinical relevance [
25]. In any case, pain per se is no contra-indication for operative management. In fact, five (3.4%) patients in the nonoperative group of the current study were operated due to disproportional pain.
Six patients out of 245 operated patients in our study had an infection (2.4%), of which five were only superficial according to the CDC classification. This is slightly less than the 3.1% out of 611 operated patients as reported in a recent meta-analysis [
2].
Sixteen (4.1%) patients presented with radial nerve palsy after trauma, which is a much lower rate than the 15.6% (201/1,289) reported in a meta-analysis [
2]. The postoperative radial nerve palsy rate in their study was 3.6%, with a full recovery rate (at follow-up ranging from 6 to 72 months) of 96.4%. In our study, nine of out 232 (3.9%) patients developed a postoperative radial nerve palsy, of whom eight showed full recovery within the 12 month follow-up. This implies that the risk of persistent radial nerve palsy due to surgery at 12 months is 0.4% (
i.e., 1/232), and this minimal risk should be no reason to avoid surgery.
An inherent disadvantage of operative management is the risk of implant-related complications. Implant removal was performed due to nail or screw protrusion or chronic pain in 16/245 (6.9%) patients who were all treated with an IMN. For the same indication, hardware removal was reported in 10/156 (6.4%) patients in one RCT and three observational studies [
23,
27‐
29].
To achieve early functional recovery, treatment should focus on timely fracture healing and preventing malalignment. In this study, malalignment only occurred after nonoperative treatment, with 11 out of 14 patients requiring revision surgery. This rate of 9.7% is in line with 11.0% as calculated from one RCT and three observational studies [
24,
27,
28,
30]. The risk of nonunion in our study was 2.6-fold higher after nonoperative treatment than after operative treatment (
i.e.¸ 26.3% versus 10.1%). Analogous to our data, another RCT and two observational studies show a 2–2.5-fold higher nonunion rate after nonoperative treatment [
23,
31,
32]. The effect was even stronger in two RCTs, which show 15 and 25% nonunion in the nonoperative group versus none at all after surgery [
24,
25]. With data supporting that nonunion can, to a large extent, be prevented by immediate surgery, surgery should be the first option for the treatment of humeral shaft fractures.
Strengths and limitation
The main strength of this prospective, multicenter study is that it is the largest series of patients with a humeral shaft fracture to date. The sample size was much higher than 47 to 110 patients in the most recent prospective studies on this topic [
24‐
26,
33,
34]. Combined with the participation of 29 hospitals across the country, including level 1, 2, and 3 trauma centers, it therewith represents current practice. Furthermore, treatment heterogeneity across participating hospitals caused by not standardizing treatment or rehabilitation will improve generalization of the results. The higher prevalence of females and higher median age in the nonoperative group in this study is in line with published data [
2]. This may also explain the higher prevalence of osteoporosis/osteopenia in the nonoperative group. Overall, this indicates that selection bias due to the study design is unlikely, based on these patient characteristics.
A benefit of the observational design, allowing surgeon to decide on treatment, surgical approach, and implant, is that surgeons could use the (operative) technique they felt was best for the individual patient in their hands. This in contrast to a randomized design where randomization could result in the (operative) technique where the surgeon would feel less comfortable with or had less experience in. Another strength is that dedicated researchers performed the follow-up measurements of all patients. This centralized coordination allowed hospitals with insufficient research resources to participate. In a previous study it was shown that data quality and completeness can benefit from central study coordination [
35].
As commonly seen in observational studies, some imbalance in baseline data was noted between the two treatment groups. Although this may be considered as a limitation, we were able to correct for this in the mixed-linear models. When designing the study, we considered a RCT not feasible. The rationale, which includes strong patient and surgeon preference and early termination of RCTs at that time due to enrollment issues, is elaborated on the published study protocol [
12].Another limitation could be that some participating hospitals enrolled < 5 patients, suggesting that not all patients were screened for participation. Overall, 46 patients were missed for screening or declined participation. Consequently, the study sample was not consecutive. As this study did not interfere with treatment decision, it is unlikely that this has introduced selection bias or affected validity of the results. On the other hand, despite great efforts of the researchers, some bias due to missed follow-up visits and consent withdrawal cannot be ruled out. As this was the case in 19% of patients in both treatment arms, this is unlikely to be differential.
Acknowledgements
Hummer Investigators: Local principal investigators and co-investigators—Ivo Beetz, MD PhD, Trauma Research Unit Department of Surgery, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands; Hugo W. Bolhuis, MD, Department of Surgery, Gelre Hospital, Apeldoorn, The Netherlands; P. Koen Bos, MD PhD, Department of Orthopaedic Surgery, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands; Maarten W.G.A. Bronkhorst, MD PhD, Trauma Unit, The Hague, The Netherlands; Milko M.M. Bruijninckx, MD, Department of Surgery, IJsselland Hospital, Capelle a/d Ijssel, The Netherlands; Jeroen De Haan, MD PhD, Department of Surgery, Dijklanderziekenhuis, Hoorn, The Netherlands; Axel R. Deenik, MD PhD, Department of Orthopaedic Surgery, Haaglanden MC, The Hague, The Netherlands; P. Ted Den Hoed, MD PhD, Department of Surgery, Ikazia Hospital, Rotterdam, The Netherlands; Martin G. Eversdijk, MD, Department of Surgery, St. Jansdal Hospital, Harderwijk, The Netherlands; J. Carel Goslings, MD PhD, Trauma Unit Department of Surgery, Amsterdam University Medical Center, location AMC, Amsterdam, The Netherlands; Robert Haverlag, MD, Department of Surgery, OLVG Hospital, Amsterdam, The Netherlands; Martin J. Heetveld, MD PhD, Department of Surgery, Spaarne Gasthuis, Haarlem, The Netherlands; Albertus J.H. Kerver, MD PhD, Department of Surgery, Franciscus Gasthuis & Vlietland, Rotterdam, The Netherlands; Karel A. Kolkman, MD, Department of Surgery, Rijnstate Hospital, Arnhem, The Netherlands; Peter A. Leenhouts, MD MBA, Department of Surgery, Zaans Medical Center, Zaandam, The Netherlands; Sven A.G. Meylaerts, MD PhD, Trauma Unit, Haaglanden MC, The Hague, The Netherlands; Ron Onstenk, MD, Department of Orthopaedic Surgery, Groene Hart Hospital, Gouda, The Netherlands; Martijn Poeze, MD PhD, Department of Trauma Surgery, Maastricht University Medical Center, Maastricht, The Netherlands; Rudolf W. Poolman, MD PhD, Department of Orthopaedic Surgery, OLVG Hospital, Amsterdam, The Netherlands; Bas J. Punt, MD, Department of Surgery, Albert Schweitzer Hospital, Dordrecht, The Netherlands; Ewan D. Ritchie, MD, Department of Surgery, Alrijne Hospital, Leiderdorp, The Netherlands; W. Herbert Roerdink, MD PhD, Department of Surgery, Deventer Hospital, Deventer, The Netherlands; Gert R. Roukema, MD, Department of Surgery, Maasstad Hospital, Rotterdam, The Netherlands; Jan Bernard Sintenie, MD, Department of Surgery, Elkerliek Hospital, Helmond, The Netherlands; Nicolaj M.R. Soesman, MD, Department of Surgery, Franciscus Gasthuis & Vlietland, Schiedam, The Netherlands; Edgar J.T. Ten Holder, MD, Department of Orthopaedic Surgery, IJsselland Hospital, Capelle a/d IJssel, The Netherlands; Wim E. Tuinebreijer, MD PhD, Trauma Research Unit Department of Surgery, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands; Maarten Van der Elst, MD PhD, Department of Surgery, Reinier de Graaf Gasthuis, Delft, The Netherlands; Frank H.W.M. Van der Heijden, MD PhD, Department of Surgery, Elisabeth-TweeSteden Hospital, Tilburg, The Netherlands; Frits M. Van der Linden, MD, Department of Surgery, Groene Hart Hospital, Gouda, The Netherlands; Peer Van der Zwaal, MD PhD, Trauma Unit, Haaglanden MC, The Hague, The Netherlands; Jan P. Van Dijk, MD, Department of Surgery, Hospital Gelderse Vallei, Ede, The Netherlands; Hans-Peter W. Van Jonbergen, MD PhD, Department of Orthopaedic Surgery, Deventer Hospital, The Netherlands; Egbert J.M.M. Verleisdonk, MD PhD, Department of Surgery, Diakonessenhuis, Utrecht, The Netherlands; Jos P.A.M. Vroemen, MD PhD, Department of Surgery, Amphia Hospital, Breda, The Netherlands; Marco Waleboer, MD, Department of Surgery, Admiraal De Ruyter Hospital, Goes, The Netherlands; Philippe Wittich, MD PhD, Department of Surgery, St. Antonius Hospital, Nieuwegein, The Netherlands; Wietse P. Zuidema, MD, Department of Trauma Surgery, Amsterdam University Medical Center, location VUmc, Amsterdam, The Netherlands. Medical students (Trauma Research Unit Dept. of Surgery, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands): Ahmed Al Khanim, Jelle E. Bousema, Kevin Cheng, Yordy Claes, J. Daniël Cnossen, Emmelie N. Dekker, Aron J.M. De Zwart, Priscilla A. Jawahier, Boudijn S.H. Joling, Cornelia (Marije) A.W. Notenboom, Jaap B. Schulte, Nina Theyskens, Gijs J.J. Van Aert, Boyd C.P. Van der Schaaf, Tim Van der Torre, Joyce Van Veldhuizen, Lois M.M. Verhagen, Maarten Verwer, Joris Vollbrandt.