*3.1. Risk of Reoperation in the Follow-Up Adjusting by Cox Regression Modeling*

The Cox regression model was used to analyze the association between the risk of reoperation and different covariates. The results of the model indicate that the type of nail (Gamma3/InterTAN) was a significant predictor of reoperation, with patients who received the InterTAN having a higher hazard ratio (HR) of 3.6 (95% CI: 1.3, 10.5) for required reoperation compared to those who received the Gamma3 nail. The results of Model 2 (Cox regression model for risk of reoperation needed) indicate that the type of nail (Gamma3 vs. InterTAN) was a significative predictor of reoperation required (Table 3), but neither the type of fracture (basicervical/other) nor age nor sex were found to be significant predictors. These results suggest that the type of nail may be an important factor in determining the risk of reoperation after surgery.

In addition to the Cox regression analysis, a Kaplan-Meier survival curve was generated to visualize the probability of required reoperation over time for the different nails. The results of the Kaplan-Meier analysis show that the probability of required reoperation was higher for patients who received the InterTAN (Figure 3a). The curve for the InterTAN group drops more steeply than the curve for the Gamma3 nail group, indicating that reoperations required were more likely to occur early on, and at a higher rate in the InterTAN group. We can see that the difference was important from one year of follow-up. Additionally, the log-rank test was performed to test the equality of the survival curves between the two groups, with a *p* = 0.001 indicating a statistically significant difference

between the groups. Overall, the Kaplan-Meier analysis provides a visual representation of the reoperation required rates, and supports the findings from the Cox regression analysis. Otherwise, we analyzed all-cause mortality and didn't find any difference between nail groups related to overall survival, *p* = 0.70 (Figure 3b).


**Table 3.** Cox regression model for risk of reoperation needed.

**Figure 3.** (**a**) Risk of reoperation needed. (**b**) Risk of all-cause mortality.

*3.2. Risk of Reoperation Evaluated after Propensity Score Matching*

We conducted a propensity score matching, which shows how the balance of the baseline covariates between the treatment groups was assessed to evaluate the success of the matching procedure. The results after propensity score matching show that the distribution of the baseline characteristics, including age, sex and type of fracture, were similar between the treatment groups, with a standardized mean difference of less than 0.1 for all covariates (Figure 4). This suggests that the propensity score matching procedure was successful in controlling for potential confounding effects of the baseline covariates on the treatment effect. Additionally, the effect of the treatment on the outcome of interest, reoperation, was found to be consistent with the results obtained before propensity score matching (HR = 3.3; *p* = 0.038).

**Figure 4.** Standardized mean difference of baseline characteristics before and after propensity score matching. The solid vertical line represents the threshold of 0.1, indicating balance between the groups. The matching procedure was successful in balancing the baseline characteristics between the treatment groups.

#### **4. Discussion**

The present study showed that in this cohort, double interlocking head screw nailing systems such as the InterTAN nail led to a significantly higher rate of reoperations compared to the Gamma3 nail. At first, it seemed that this finding could be associated with the fracture pattern, as there was a heterogenous distribution of types of fracture. However, no significant differences were found in any other indicators between the two groups, including type of fracture, sex or age.

Although there is some scientific biomechanical proof of the rotational stability of InterTAN nails [5], in clinical studies and reviews, there is still controversy between the existing types of nails [6–17]. A priori, this increase in rotational stability would be advantageous in basicervical fracture traces by avoiding rotation of the cervical neck when drilling or inserting the cephalic screw. However, this supposed biomechanical advantage was not reflected in the patients in the study who underwent surgery.

There have been two Cochrane reviews about trochanteric fracture treatment [3,7]. One compares nails to extramedullary implants [4] and another compares the different types of nails [8]. In the latter review, Queally et al. analyzed 17 randomized clinical trials (RCTs) prior to 2014, compared different nails and concluded that there was insufficient evidence from randomized trials to determine if there are important differences in patient outcomes between the different designs of proximal femoral intramedullary nail produced by different manufacturers when used for the fixation of unstable, or stable, trochanteric fractures [7].

There are also more recent clinical trials and meta-analyses comparing different nails and it continues to be uncertain whether there is a difference between implants. Two RCTs specifically compared Gamma3 to InterTAN with similar results [8,9]. Su et al. concluded that no significant difference was found in X-ray times, reduction results, TAD, time to mobilization, operative complications, femoral neck shortening or fracture healing time [8]. Berger et al. affirmed that, in terms of implant-related complications, no significant differences were recorded [9]. Zhang et al. have several studies, including one RCT, comparing InterTAN to PFNA-II in which they didn't find any significant differences in outcomes except for high pain [10–12]. Ülkü et al. retrospectively studied nail migration. Although there was a significant difference in favor of InterTAN, nail migration in the PFNA group did not result in reoperation [13]. Ricci et al. also found a higher radiological collapse in PFNA and DHS vs. InterTAN, but they don't mention whether that has clinical repercussions [14]. The Liu et al. meta-analysis included two RCTs and seven observational studies, and concluded that patients with the InterTAN nail had a lower risk of screw migration, pain at thigh or hip, cutout, varus collapse of the femoral head, femoral shaft fracture and reoperation. Nonetheless, that finding was based mainly on observational studies, as the researchers didn't find superiority in cutout, reoperation and femoral shaft fracture when considering only the RCTs [15]. There are two other meta-analyses that suggest that InterTAN leads to fewer complications when compared to single screw devices. However, both of them include mainly retrospective studies and both have conflicts of interest, as they were done by Smith and Nephew collaborators [16,17].

Although we have not screened every patient included in the study for osteoporosis, we can affirm that most patients suffered from it to a greater or lesser degree due to their age, comorbidities and the fact that they had suffered the fracture from a low energy impact. A plausible explanation for these results could be the greater aggression to both the head and the femoral neck caused by the integrated double screw. The double reaming performed, coupled with the fact that the double screw system is thicker than the single screw, could further weaken the cortices and the vascularization of an already-weakened bone, increasing the risk of osteosynthesis failure in certain cases.

However, there are several inherent limitations to our study that deserve consideration. First, the retrospective nature presents a potential selection bias. Patients were distributed between treatment groups based on surgeon preference and we didn't consider the surgeon's experience in our analysis. Additionally, the pattern of fracture was heterogeneously distributed in both groups and the number of cases is low. Although adjustment was made for several variables, it is possible that residual confounders between the nails could still be present, and therefore the adjusted cox regression and propensity score matching may not be able to adjust or balance all unmeasured confounders. In our center, immediate postoperative radiographs are performed by radiology technicians without the direct supervision and approval of a traumatologist. In several patients, the axial projection of the hip was not performed correctly or was not performed at all. Due of this, it was not possible to perform a correct measurement of the tip-apex distance in all patients, so it was decided not to include it in the study parameters. Lastly, single-center studies lack the external validation required to support changes in practice, so we recommend interpreting these results with caution.

## **5. Conclusions**

Single head screw nails such as Gamma3 and dual integrated compression head screw nails such as InterTAN may be effective for surgical treatment of trochanteric fractures.

A higher risk of reoperation was found when using InterTAN. Therefore, despite the potential biomechanical benefits of using two screws with the InterTAN nail, we cannot recommend it over the Gamma3 nail.

Large-sample multicenter studies may be needed in the future to compare the different cephalomedullary nails available.

**Author Contributions:** Conceptualization, M.M.M.-O.; methodology M.M.M.-O.; software A.H.-R. and M.A.G.-B.; validation, J.L.P.-B.; formal analysis, A.H.-R., M.A.G.-B. and H.G.-P.; investigation, M.M.M.- O.; resources, M.M.M.-O.; data curation, A.H.-R., M.A.G.-B. and J.Á.-d.l.C.; writing—original draft A.H.-R.; preparation J.Á.-d.l.C. and A.H.-R.; writing—review and editing, N.Á.-B.; visualization, N.Á.-B. and J.Á.-d.l.C.; supervision, J.L.P.-B.; project administration, M.M.M.-O.; funding acquisition, not necessary. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research received no external funding.

**Institutional Review Board Statement:** The study was conducted in accordance with the Declaration of Helsinki, and approved by the Institutional Review Board (or Ethics Committee) of University Hospital of the Canary Islands (protocol code CHUC\_2021\_134; date of approval: 27 January 2022).

**Informed Consent Statement:** Informed consent was obtained from all subjects involved in the study.

**Data Availability Statement:** The data presented in this study are openly available in Figshare at https://doi.org/10.6084/m9.figshare.21548340.v2 (accessed on 3 May 2023).

**Conflicts of Interest:** The authors declare no conflict of interest.
