Muscle pedicle bone flap transplantation for treating femoral neck fracture in adults: a systematic review

Background This systematic review was conducted to gather available evidence on the effectiveness of muscle pedicle bone flap transplantation in adult patients with femoral neck fractures. Methods Databases such as PubMed, EMBASE, IEEE, Web of Science, and Cochrane library were searched from their dates of inception until March 2021. Two reviewers independently selected the interventional studies on the assessment of the effectiveness of muscle pedicle bone flap transplantation for femoral neck fractures; data extraction and assessment of the methodological quality as per the Institute of Health Economics quality appraisal checklist were also performed by the reviewers. The effectiveness and complication outcomes were assessed by calculating the average rates. Results Overall, 20 studies with 1022 patients were included in this review. Notably, the methodologic quality of the included studies was typically poor. The average effective rates were as follows: good, 73.4%; fair, 15.4%; and poor, 10.9%. Moreover, the average nonunion rate, average avascular necrosis rate, average collapse rate, and the overall reoperation rate were 9.0%, 6.7%, 4.7%, and 7.3%, respectively. Conclusions This systematic review of heterogeneous studies with varying number of patients and varying surgical techniques indicated that muscle pedicle bone flap transplantation provides promising results with low rates of avascular necrosis and nonunion. Nevertheless, further controlled studies are required to ascertain the effectiveness of muscle pedicle bone flap transplantation in treating femoral neck fracture.


Background
Hip fracture is associated with limited movement, chronic pain, disability, loss of independence, and decline in the quality of life. Moreover, approximately 20-30% of patients with hip fractures die within a year [1,2]. Notably, femoral neck fracture is the most common type of hip fracture. Femoral neck fracture treatment is typically classified into conservative and surgical treatments. Nevertheless, because conservative treatment requires long-term bedrest, the incidence of complications such as pulmonary infection and thrombosis is high. Therefore, most clinicians recommend surgical treatment as the first-line of treatment in old patients with femoral neck fracture [3]. Surgical treatment of displaced intracapsular neck fractures in patients aged more than 70 years entails hip replacement with a partial or total prosthesis-a modality accepted by a vast majority of researchers worldwide. Nonetheless, the conservative treatment is typically recommended in younger patients (< 60 years). Moreover, complications such as fracture nonunion and osteonecrosis of the femoral head can easily occur after the femoral neck fracture [4]. The current, tried, and tested surgical treatment methods for ununited femoral neck fractures are internal fixation, internal fixation plus osteotomy with or without bone graft, non-vascularized or vascularized bone graft, and hip arthroplasty [5]. Nevertheless, in developing countries, various factors such as illiteracy, low socioeconomic status, ignorance, and poor medical facilities might cause a delay in surgical treatment. Squatting and sitting cross-legged are inherently involved in the activities of daily living, particularly in a developing country such as India. Therefore, considering the needs of such patients, as well as the cost of joint replacement surgeries, salvaging the femoral head is of paramount importance, and several patients opt for femoral head salvage surgery.
The surgical treatment of femoral neck fracture remains controversial despite several advancements in the orthopedics domain. Nonunion and avascular necrosis are the two major complications of this fracture. Although the rate of nonunion has been reduced through anatomical reduction and stable fixation of fractures, the incidence of avascular necrosis is high [6]. In 1962, an autogenous muscle pedicle graft from the quadratus femoris muscle was used for the first time [7]. In addition, the application of fresh autogenous cancellous iliac bone chips along with muscle pedicle bone grafting has been reported to provide excellent outcomes [8]. However, whether muscle pedicle bone flap transplantation is effective in treating femoral neck fractures remains inconclusive.
It is very important to determine the effectiveness of muscle pedicle bone flap transplantation and its potential related factors. This not only builds a bridge between clinical and basic or translational science, but also for complex surgical problems, it is necessary for clinicians to understand the disease process, integrate new concepts into their surgical techniques, integrate new scientific discoveries, and improve the operation practice in the operating room [9,10].
Therefore, this systematic review analyzed the available evidence on the efficacy and safety of muscle pedicle bone flap transplantation for femoral neck fractures in adults.

Methods
A systematic review was performed in accordance with the Cochrane Systematic Review Guidelines and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist [11,12]. This systematic review is based on the literature. All previously published studies were analyzed, and thus, ethical approval and patient consent were not required.

Search strategy
Databases including PubMed, EMBASE, IEEE, Web of Science, and Cochrane library were searched from their date of inception until March 2021 to identify studies that have assessed the efficacy of muscle pedicle bone flap transplantation in treating femoral neck fracture. No language restrictions were applied. The following search terms were used: "femoral neck fracture," "fracture of femoral neck," "muscle pedicle," "bone flap," and "bone grafting." In addition, the references of all the retrieved articles, including the relevant systematic reviews, were manually searched for additional relevant articles.

Study selection criteria
The inclusion and exclusion criteria for population, intervention, comparison, outcomes, and study were defined and applied.

Participants
Participants include adult patients diagnosed with femoral neck fractures, including displaced femoral neck fracture, ununited femoral neck fracture, and neglected femoral neck fracture. However, trials focusing on the treatment of patients with fracture not limited to femoral neck as well as reoperation were excluded.

Intervention and comparison
This review included studies on any type of muscle pedicle bone flap transplantation involving tensor fascia lata muscle, gluteus medius muscle, quadratus femoris muscle, and sartorius muscle pedicle bone grafting. However, studies that focused on bone grafting without muscle pedicle were excluded.

Outcomes
Primary outcomes were nonunion and avascular necrosis rates, whereas the secondary outcomes were the collapse rate, reoperation rate, and effective rate. Studies that did not report the eligible outcomes or data were excluded.

Study
Published or unpublished randomized controlled trials (RCTs) or non-RCTs were selected. In addition, case series were included. However, reviews or animal experiments were excluded.
The selection of studies was conducted independently by two reviewers. After removing duplicates, the reviewers screened the titles and abstracts of all the identified studies. Full text of all articles with potential relevance were retrieved for comprehensive assessment as per the inclusion criteria. Any disagreement was resolved through consensus with a third reviewer.

Data collection and analysis
All study characteristics and data, such as study population, sample size, and outcomes, were extracted as per the predefined criteria. Two authors independently extracted the data using a data extraction form. Any potential disagreement between the authors was resolved, and consensus was established through discussion involving a third author.

Quality assessment
In addition, two authors independently evaluated the methodological quality. The case series was assessed on the basis of the Institute of Health Economics quality appraisal checklist form [13]. This 20-criterion checklist has eight aspects, namely, study objective, study design, study population, intervention and co-intervention, outcome measures, statistical analysis, results, and conclusions, as well as competing interests and sources of support. Notably, criteria such as prospective study, consecutive recruitment, predefined inclusion or exclusion criteria, before and after outcome measurement, and sufficient follow-up data were used to examine how the study was executed, whereas other criteria (such as a clear statement of study objective, description of patient characteristics, interventions and co-interventions, reporting of adverse events, competing interests, and sources of support) focused on the reporting quality. The items were rated as follows: yes, unclear or partial, and no. Any discrepancies were resolved through discussion between all the authors.

Statistical analysis
Notably, both meta-analytical and level of evidence approaches were deemed inappropriate to formulate conclusions because of the inadequacy of comparison. The average nonunion, avascular necrosis, collapse, reoperation, and effective rates were calculated on the basis of the sum of the number of patients who experienced these events divided by the sum of the number of patients who received muscle pedicle bone flap transplantation.

Study characteristics
All the included studies were published between 1973 and 2020. Of the included studies, four were retrospective in nature; two, case-control studies; one, a nonrandomized control trial; and the remaining were case series. No RCT was included in this systematic review. Of the 20 publications, 3 were from the USA, 5 were from China, 1 was from Turkey, and the remaining were from India. The procedures used in these studies included quadratus femoris muscle pedicle bone grafting with screw fixation, open reduction and internal fixation, tensor fascia lata, and gluteus medius muscle pedicle bone grafting. Moreover, the included studies focused on patients with femoral neck fractures, mainly displaced fracture of the femoral neck, ununited femoral neck fractures, transcervical or subcapital fractures of the femoral neck, and neglected femoral neck fracture. Table  1 lists the characteristics of the studies included in the present meta-analysis. Table 2 presents the methodological quality of the studies. Losses to follow-up, adverse events, and the conclusions supported by the results were reported in all but one study [14]. The objective was not clearly stated in one study [30]. Except for four studies, all the studies were conducted prospectively [18,21,27,31]. Only three studies recruited consecutive patients [14,23,25]. Regarding intervention and co-intervention, except for two studies, all the studies clearly described the intervention of interest [15,19]. All studies except three [15,19,32] had clearly described the additional interventions. Regarding the outcome measures, no study had reported the statistical tests used to appropriately assess the relevant outcomes, except for two, which provided estimates of random variability in the data analysis of relevant outcomes [14,15]. Overall, the methodological quality of the included studies was generally poor.
The collapse rate was reported by 6 studies with 471 patients, and its 95% CI ranged from 3.0 to 6.8% (average, 4.7%). The reoperation rate was reported by eight studies that enrolled 546 patients, and its 95%CI ranged from 2.9 to 13.4% (average, 7.3%). The summary of complications is listed in Table 3.

Effectiveness outcome
The effective rate was reported by 10 studies involving 612 patients; of these, three used self-established criteria [27][28][29], four used the modified Harris hip score [16,18,21,25], one used the Salvati and Wilson score [20], one study used the Sanders score [22], and one study used the modified Postel and Merle d'Aubigne hip scoring to assess the effective rate [19]. An average effective rate of 73.4% were considered good, while rates of 15.4% and 10.9% were considered fair and poor, respectively. Table  3 presents the summary of the efficacy outcome.

Summary of evidence
We identified 20 studies that met our inclusion criteria. These studies included 1022 adult patients with femoral neck fractures who were treated with muscle pedicle bone flap transplantation. Notably, our systematic review indicated an average good effective rate of 73.4% for the muscle pedicle bone flap transplantation. Furthermore, the nonunion rate of muscle pedicle bone flap    transplantation was 9.0%, the avascular necrosis rate was 6.7%, the collapse rate was 4.7%, and the reoperation rate was 7.3%. One case series and literature review had summarized the evidence of muscle pedicle bone flap transplantation application in treating femoral neck fractures in adults [15]. However, the review included only six studies, and no quality assessment was conducted in the review. In that review, the muscle pedicle bone flap was compared with other treatments for delayed or ununited fractures of the femoral neck, and it claimed that the vascularized iliac crest, fibular, and periosteal grafting procedures are not popular procedures due to their time-consuming and technically demanding nature as well as due to the need for high competency from average orthopedic surgeons. Furthermore, despite the high union rate of such vascularized bone grafting series, these reviews were small and had short follow-up durations; therefore, it is challenging to predict the future occurrence of avascular necrosis in such patients. Conversely, the follow-up duration in the studies included in our systematic review was longer; the duration was approximately 3 years in 10 studies, and considerably longer in other studies (e.g., the average study duration in one study was 150 months), which is sufficiently long to predict the future occurrence of avascular necrosis rate in those patients.

Nonunion and avascular necrosis rates of muscle pedicle bone flap transplantation
Femoral head viability remains a major concern in femoral neck fractures. The two most challenging complications of femoral neck fractures in young adults are femoral head osteonecrosis and nonunion. Notably, osteonecrosis is a devastating complication in young patients due to the limited availability of options for young patients compared with that for elderly patients with the same condition afflicting the femoral head [5]. Despite advancements in surgical techniques, instrumentations, and imaging modalities, complications such as nonunion (10-30%) and avascular necrosis (15-33%) persist in affected patients [33,34]. The average nonunion and avascular necrosis rates of muscle pedicle bone flap transplantation in our systematic review of 14 studies were less than 10%. Moreover, bone grafting has evolved as a treatment modality for these fractures with predictable results in the long term. Furthermore, if used along with internal fixation in neglected femoral neck fracture, the vascularized bone grafting on a muscle pedicle, such as gluteus medius, quadratus femoris, or sartorius, further supplies blood to the femoral head by acting as a vascular inlay graft and structural bone graft to buttress the posterior femoral neck comminution and enhances stability, thereby improving osteosynthesis [35]. Nevertheless, risk factor analysis for nonunion and avascular necrosis rates was not performed in these studies; therefore, the systematic review could not provide suggestions to doctors regarding the nonunion and avascular necrosis rates.
Nonetheless, the muscle pedicle bone grafting approach is associated with the risk of extensive dissection and blood loss, particularly the risk of injuring the medial femoral circumflex artery. Commonly encountered problems with this approach are the need for experienced surgeons with excellent technical skills, long procedural duration, extensive soft tissue dissection, blood loss, and high risk of postoperative shock and infection [8]. Moreover, any torsion or tension in the muscle pedicle must be avoided when transferring the muscle pedicle bone graft to its recipient site [36]. The average duration of anesthesia and surgery in patients was 3.44 h. Time variations could be attributed to differences in the skill and experience of the surgeon.

Limitations of this review
Our literature search was comprehensive without any language restrictions; however, we cannot rule out the availability of other small and unpublished trials. Moreover, the evidence in this review is limited because of the small sample sizes and low methodologic quality of the included studies. Notably, half of these studies had  [29,34]. Furthermore, most of the studies did not report the details pertaining to the diagnosis of the collapse and nonunion rates; thus, the consistency in these rates across the included studies could not be guaranteed. In addition, more than half of the studies (11 of 20) were from India, which may induce a risk of bias. Moreover, there was no comparison of these case series, and thus, no meta-analysis could be conducted. Because most of the case series did not assess hip function by using functional parameters, such as the modified Harris hip score or Postel and Merle d'Aubigne's hip scoring, this review could not evaluate the functional recovery.
Based on the results of the present analysis of 20 articles, we found that the average effective rate of muscle pedicle bone flap transplantation was 73.4%, with a nonunion rate of 9.0%, avascular necrosis rate of 6.7%, collapse rate of 4.7%, and reoperation rate of 7.3%. Our study has relatively low rates of nonunion and avascular necrosis, and if performed along with internal fixation and grafting of the vascularized bone on a muscle pedicle, it can provide further blood supply to the femoral head, enhance stability, and improve blood supply to the femoral head. However, risk factor analyses for nonunion and avascular necrosis rates were not performed in these studies; therefore, the systematic review could not provide suggestions to doctors regarding the nonunion and avascular necrosis rates.

Conclusions
Our systematic review of heterogenous studies with varying numbers of patients and varying surgical techniques indicated that muscle pedicle bone flap transplantation provides promising results with low rates of avascular necrosis and nonunion. Nonetheless, further research is needed to confirm the efficacy of muscle pedicle bone flap transplantation in treating fracture of the femoral neck.
Abbreviations IHE: Institute of Health Economics; PICOS: Population, intervention, comparison, outcomes, and study; RCTs: Randomized controlled trials