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58 (); 140-145
doi:
10.1016/j.jor.2024.07.005

Non-vascularised fibula as an adjuvant in the management of diaphyseal humerus non-union- A meta-analysis and systematic review

Department of Biochemistry, Government Medical College and Hospital, Sector 32, Chandigarh, India
Department of Orthopaedics, Post Graduate Institute of Medical Education and Research, Sector 12, Chandigarh, India

⁎Corresponding author: Himanshu Bhayana. himanshu.bhayana.mamc@gmail.com

Disclaimer:
This article was originally published by Reed Elsevier India Pvt. Ltd. and was migrated to Scientific Scholar after the change of Publisher.

Abstract

Abstract

There is no standard protocol for managing non-union of diaphyseal humerus bone, with several authors reporting their results using various techniques and methods for its management. No meta-analysis has reported the results of managing these cases with non-vascularized fibula grafting as an adjuvant for osteosynthesis.

This meta-analysis was performed to estimate the pooled data for calculating the union rates in diaphyseal humerus fractures managed with non-vascularized fibula grafting. Risk of Bias was computed using the Joanna Briggs Institute appraisal tool.

A total of 5 studies, comprising 102 patients, were included. The pooled estimate demonstrated that 94 patients achieved bone union with intramedullary fibular strut grafting. The pooled union rate (per 100 events) was 90.59 (95 % CI, 82.86–95.04, I2 = 0). The present meta-analysis also showed a significant improvement in DASH scores following the use of a non-vascularized fibula graft with a common effects model (SMD = 4.08; 95%CI: 3.44; 4.72; p < 0.01 I2 = 19 %, p-value for Q test = 0.29).

Non-vascularized fibula grafting is an excellent adjuvant for the internal fixation of non-union diaphyseal humerus fractures. Although there is limited literature, further studies should highlight and assess the treatment of these uncommon but disabling conditions.

Keywords

Humerus
Non-union
Fibula graft
Meta-analysis
1

1 Introduction

Conservative management is the standard of care for managing isolated shaft of humerus fractures, which typically results in excellent functional outcomes and a high union rate.1,2 After surgical management, the non-union rate ranges from 8 % to 13 %.2,3 Non-union of the humerus bone leads to severe disability and pain. The management aims to provide the union of the humerus along with correction of deformity and provide the patient with a functional upper extremity. This aim is achieved by creating a healthy biological environment in the humerus, thus aiding fracture healing. Conventional management options for these cases include ORIF (open reduction internal fixation) using intramedullary nails or plates with adjuvant bone grafting.4–7 Conventional treatments such as open reduction and internal fixation (ORIF), bone grafting, or using intramedullary nails or external fixators have exhibited mixed outcomes, leading to exploring alternative strategies. Among these approaches, fibular strut graft has gained prominence recently. Studies have reported positive outcomes and have investigated the efficacy of intra-medullary fibular strut grafts in humeral shaft non-union. The fibula is a very suitable bone donor for the management of these cases because of its shape, mechanical strength, and length it provides.8

Adequate patient selection, meticulous surgical technique, and appropriate postoperative rehabilitation are pivotal in achieving favourable outcomes. Despite encouraging results, the literature reporting management of diaphyseal non-union of the humerus with autologous non-vascularized fibula graft is sparse. To the best of our knowledge, there has yet to be a meta-analysis that has consolidated this approach's union rate. Therefore, we conducted this meta-analysis to evaluate the union rate of non-vascularized fibular grafts as an intramedullary strut in treating humerus shaft non-union.

2

2 Methods

2.1

2.1 Information sources, literature search, and study selection

A comprehensive and methodical search of electronic databases for literature, including PubMed/Medline, Embase, and Scopus, was conducted for the articles. The search was performed from inception till December 04, 2023 without any limits. The search terms included: (Humerus non-union OR Humeral non-union OR Non-union humerus bone OR Non-union humerus bone) AND (Fibula grafting OR Non-vascular fibula grafting OR non-vascularized fibular grafting OR non-vascular fibular graft). The detailed search strategy is displayed in the supplementary material. Meanwhile, references from retrieved papers were checked for additional studies. Data from research papers were considered, and data from any meeting or conference abstracts were excluded from the study. The titles were combined, and duplicates that were found were removed. The remaining titles were initially screened to identify relevant items. The titles eligible for full-text screening were then sought for pertinent information. Those who did not have relevant details were excluded for various reasons. Two reviewers (TKS and DK) performed these steps independently, and any discrepancy was solved by discussion with a third reviewer (HB). No automation was used for any of the steps.

2.2

2.2 Inclusion and exclusion criteria of studies

Research articles were included in this meta-analysis if they provided information regarding the number of cases in which non-vascularized fibula grafting was used for osteosynthesis in the setting of the diaphyseal non-union of the humerus bone. Letters to the editor, short reports, editorials, commentaries, Conference abstracts, cases or small series of cases of less than 10, The meta-analysis did not include reviews, publications written in languages other than English, studies done on animals or cell lines, or research articles that did not have full textual were excluded. We included articles irrespective of the time of publication and type of publication (full article or abstract).

2.3

2.3 Data extraction

Data from each eligible study were extracted independently by two reviewers (TKS, HB), and then discrepancies were removed with consensus. We extracted information regarding the year of publication, place of study, nature of the study (prospective or retrospective), the target population (diaphyseal shaft humerus non-union managed with non-vascularized fibula graft, mean age, gender, time to union and the follow-up period). A third and fourth reviewers (VB & AB) reviewed the extracted data to ensure there were no mistakes or duplicates. Disagreements were settled through discussion by all researchers.

2.4

2.4 Data analysis

We performed all analyses using R version 4.3.2.9 The packages of meta and metafor, in addition to the base package, were used for analyses. We estimated the overall pooled estimate of the prevalence rate of union. We planned to do a summative analysis only if at least three studies were available for a particular outcome. We planned to report only the common effects model because there were no differences in the underlying population and outcome measures. After logit transformation, the pooled estimate of the union rate was calculated using the common intercept logistic regression method. For ease of understanding, events were reported as per 100 patients. Heterogeneity was assessed using the I2 values and p-value of the Q test. Any I2 > 50 was considered significant.

2.5

2.5 Risk of bias

The risk of bias for studies reporting the prevalence of target events was assessed using the Joanna Briggs tool for prevalence studies.10 Publication bias was evaluated using the visual symmetry of funnel plots and statistical tests of Begg's.11

3

3 Results

3.1

3.1 Study Selection

After combining the records from Pubmed, Embase, and Scopus. The systematic search identified a total of 165 records. After removing 53 duplicate records, the remaining 112 publications were screened, and studies were selected for full-text assessment review (Fig. 1. PRISMA flow chart).12 After evaluating these studies for eligibility, 15 were excluded because they did not match the eligibility criteria (Supplementary Material Table 2). Finally, 5 articles met the eligibility criteria and were included in our meta-analysis.13–17

PRISMA flowchart showing the process of study screening and selection.
Fig. 1 PRISMA flowchart showing the process of study screening and selection.
3.2

3.2 Study characteristics

Table 1 summarises the characteristics and main findings of the included studies. A total of 5 studies were included in our meta-analysis. Four of these five studies were retrospective and one was retrospective and prospective. All studies had been published as full papers. Two studies were conducted in India, 1 in the USA, 1 in Egypt and 1 in Saudi Arabia. One study was published before 2010 and the other four were published after 2010.

3.3

3.3 Union rates in patients of non-union of humerus diaphyseal fracture following the use of a non-vascularized fibula graft

The number of cases from the five included studies concerning non-union of diaphyseal humerus fracture who underwent fixation using non-vascularized fibula grafting was 102. Bony union was achieved in 94 patients out of these 102 cases. The pooled estimate of the union rate was 90.59 per 100 events [95 % confidence interval (CI), 82.86–95.04, I2 = 0] (Fig. 2). We calculated the event using the inverse variance method (Events per 100 observations). These quantitative results in the Forest plot (Fig. 2) suggest that there was little heterogeneity (I2 = 0 %; p = 0.83) between studies by applying the common effects model or random effects model for pooled analysis, so we used the common effects model for pooled analysis. Baujat plot showed the contribution of each study in the overall heterogeneity (Supplementary material, Fig. 1).

Forest plot showing the pooled union rates in patients of non-union of humerus diaphyseal fracture who underwent fixation using non-vascularized fibula grafting.
Fig. 2 Forest plot showing the pooled union rates in patients of non-union of humerus diaphyseal fracture who underwent fixation using non-vascularized fibula grafting.
3.4

3.4 DASH score before and after achieving union

The preoperative and final postoperative mean values and SD of DASH score were available in 3/5 studies (Table 1).15–17 The remaining 2 studies did not provide us with the required data and, hence, were not included in the pooled analysis for the DASH score calculations. These scores were pooled to give a total estimate of the overall effect. No significant heterogeneity (I2 = 19 %, p-value for Q test = 0.29; Fig. 3) was found across studies, thus the Common-effects model was used to compute the pooled effect size. The result based on the Common-effects model showed that the DASH score decreased (SMD = 4.08, 95%CI: 3.44–4.72, z = 12.44, p < 0.01, Fig. 3) at the final follow-up. The pooled SMD and (95 % CI) were 4.08 and (3.44–4.72). The overall effect size for SMD calculated as Z was 12.44 (p < 0.01; Fig. 3).

Table 1 The studies included in the systematic review with characteristics of included population.
Author and year Country Type of study Number of cases Mean Age (In years) Sex (Female/Male) Time Lapse between Primary fixation and Non Union (weeks) Cases with union achieved Time to Union in weeks (range) Pre-Op Mean DASH score Post-Op Mean DASH score
al-Zahrani S 1993 Saudi Arabia Retrospective 27 22.7 5/22 NP 25 41.2 (8–312) NP NP
Kashayi-Chowdojirao S2017 India Retrospective + Prospective 17 40.11 3/14 53.16 (6–168) 15 14 (12–20) 59.14 ± 9.62 23.4 ± 8.16
Fink Barnes LA 2020 USA Retrospective 13 60.7 11/2 NP 13 NP NP 38.1 ± 27.6
Sadek A 2021 Egypt Retrospective 33 40.3 13/20 108 (48–224) 29 30 (12–48) 49.4 ± 12.1 7.7 ± 8.9
Shetty K 2022 India Retrospective 12 50.7 NP 32 (24–156) 12 17 (12–24) 61 ± 6.7 28.8 ± 4.4
Forest plot showing the pooled DASH score in patients before union (preoperative) of humerus diaphyseal fracture and after union (postoperative) of humerus diaphyseal fracture by using a non-vascularized fibula graft.
Fig. 3 Forest plot showing the pooled DASH score in patients before union (preoperative) of humerus diaphyseal fracture and after union (postoperative) of humerus diaphyseal fracture by using a non-vascularized fibula graft.
3.5

3.5 Risk of bias

The visual assessment of the Funnel plot (Fig. 4) suggested that many of the studies were on the right of the funnel, but Begg's test showed no evidence of publication bias (p = 0.1416). This observation indicates the funnel plot asymmetry could be related to the high heterogeneity. All studies had high quality based on the Joanna Briggs Institute critical Appraisal Tool (Supplementary Material Table 3). The risk of bias as assessed by JBI and all 5 included studies showed a low risk of bias (Supplementary Material Table 3). Figs. 5 and 6 reveal the Risk of Bias by Domain and the Risk of Bias stacked bar graph for each domain respectively.

Funnel plot to visually assess the publication bias of included studies.
Fig. 4 Funnel plot to visually assess the publication bias of included studies.
Risk of bias by domain.
Fig. 5 Risk of bias by domain.
Risk of Bias stacked bar graph for each domain.
Fig. 6 Risk of Bias stacked bar graph for each domain.
4

4 Discussion

The present meta-analysis, a first evaluating the union rate of diaphyseal non-union of humerus bone managed with non-vascularized fibula grafting, suggests that using non-vascularized fibula as an adjuvant to internal fixation is a viable option for treating these cases. The pooled rate of union was more than 90 % in these cases. Fibula grafting involves harvesting and transplanting a fibula segment to provide structural support. This technique has evolved, with various modifications, to enhance biomechanical stability and promote bone healing. The method works well in cases of diaphyseal non-union scenarios. Fibula as a graft option has several assets; it is a composite graft structurally and biologically and facilitates healing by providing osteoconductive and osteogenic properties. The fibular graft, an autograft, also minimizes the risk of graft rejection or infection risk. The fibula as a graft can be vascularized as well as non-vascularized. The present study's focus was to look only at the cases in which non-vascularized fibula grafting was used, and the cases or the studies involving the use of vascularized fibula grafts were excluded.

Persistent non-union of the humerus results in continuous disability and unremitting pain in the affected upper limb. The condition is known to require several surgical procedures for its management. Attempts to treat non-union of the humerus so far have been non-standardized, multimodal, and often unsuccessful.14 The pooled data demonstrates that the concept of non-vascularized fibula graft as an adjuvant to managing non-union of humerus bone results in a high union rate, negating the need for further surgeries. The fibula graft has various advantages. The fibular strut graft acts as a mechanical strut, reinforcing the stability of the fractured humerus. This mechanical support is crucial in cases where traditional fixation methods have failed, and there is a need for additional structural reinforcement. Biologically, the fibular graft functions as a scaffold for new bone formation, providing an environment conducive to osteogenesis at the non-union site. Combining mechanical stability and biological enhancement, this dual role positions intra-medullary fibular strut grafts as a comprehensive solution for the intricate challenges of humeral shaft non-union. The fibular graft, an autograft, also minimizes the risk of graft rejection or infection risk.18

Compared to DBM (Demineralized Bone Matrix) or cancellous allografts, it is cortico-cancellous. Therefore, it has a structural integrity, which helps resist forces against compression and bending. This property helps reduce stress during osteosynthesis assembly. In addition, the strut graft enhances the strength of the screw fixation by providing an improved bone matrix, which results in a stable repair of the osteosynthesis.19,20 The cortical bone graft revascularizes predictably, albeit slowly. Until the stage of graft incorporation by creeping substitution, the fibula acts like filler for the medullary canal and prevents abnormal mobility to the humerus.

Another significant advantage of this technique is that it does not involve advanced equipment or super-specialized training for harvesting the vascularized pedicle for the fibula graft. The vascularized fibula grafting techniques are technically more challenging and have a steep learning curve. On the other hand, there is a possibility of donor site morbidity, including infection, pain at the graft site, transient nerve injury, graft resorption, hardware failure, etc., which may arise, emphasizing the importance of meticulous surgical technique and postoperative care. However, such complications have been rarely reported in the literature.21

A total of 5 studies, comprising 102 patients, were included in the meta-analysis. The primary outcome measure was to analyse the bone union rates from the included studies. The pooled data demonstrated a 90.59 % overall success rate in achieving bone union with intramedullary fibular strut grafting. We also looked at the reported functional outcomes of the included studies. The present meta-analysis showed that DASH scores significantly decreased at the final follow-up.

Our study has its share of limitations; we did not include any control group and reported only on the prevalence of united cases among those who received a particular mode of treatment. The study has certain strengths. As such, it is the first study estimating the pooled union rates in the select group of the diaphyseal non-union of the humerus bone, and we had a fair number of desired populations arising from 5 studies. Further, the study reports the lacunae in the literature, which provides ground for further studies in the same field.

5

5 Conclusion

Managing non-union in the shaft of the humerus with a fibula strut graft represents a viable and effective surgical option. This technique offers a simple solution to restore stability, promote bone healing, and improve overall function. With ongoing research and advancements in surgical techniques, using fibula strut grafts to manage humeral shaft non-union holds great promise for improving patient outcomes and quality of life.

Source of financial support in the form of grants

None.

Registration number in case of clinical trials

Not applicable.

Ethical clearance from the institute

Not Applicable.

Patient consent

Not applicable.

Declarations

The authors have no conflicts of interests associated with this article.

The study was not supported by grants, drugs or other support.

CRediT authorship contribution statement

Tarun Kumar Sharma: Conceptualization, Search, Screening and Study Selection, Methodology, RoB, Formal analysis, Writing – original draft, Writing – review & editing, Final approval. Deepak Kumar: Conceptualization, Screening, Writing – original draft, Writing – review & editing. Aditya Gupta: Screening, Writing – original draft, Writing – review & editing. Vikas Bachhal: Screening, Writing – original draft. Arjit Bansal: Writing – original draft. Himanshu Bhayana: Conceptualization, Search, Screening and Study Selection, Methodology, RoB, Writing – original draft, Writing – review & editing, Final approval.

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