Advertisement

Vascularised versus non-vascularised bone graft for scaphoid nonunion: Meta-analysis of randomised controlled trials and comparative studies

Open AccessPublished:December 16, 2022DOI:https://doi.org/10.1016/j.jpra.2022.12.001

      Summary

      Background

      Numerous studies have investigated surgical techniques for vascularised bone graft (VBG) for scaphoid nonunion; however, their efficacies remain unclear. Thus, to estimate the union rate of VBG for scaphoid nonunion, we performed a meta-analysis of randomised controlled trials (RCTs) and comparative studies.

      Methods

      A systematic search was conducted using PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials. The search formula was as follows: ((scaphoid nonunion) OR (scaphoid pseudarthrosis)) AND (bone graft). Only RCTs were used in the primary analysis, and comparative studies, including RCTs, in the secondary analysis. The primary outcome was nonunion rate. We compared the outcome between VBG and non-vascularised bone graft (NVBG), pedicled VBG and NVBG, and free VBG and NVBG.

      Results

      This study included a total of 4 RCTs (263 patients) and 12 observational studies (1411 patients). In the meta-analyses of both RCTs only and RCTs and other comparative studies, no significant difference in nonunion rate was found between VBG and NVBG (summary odds ratio [OR], 0.54; 95% confidence interval [CI], 0.19–1.52 and summary OR, 0.71; 95% CI, 0.45–1.12), respectively. The nonunion rates of pedicled VBG, free VBG, and NVBG were 15.0%, 10.2%, and 17.8%, respectively, and no significant difference was found.

      Conclusions

      Our results indicated that the postoperative union rate in NVBG is similar to that in VBG; thus, NVBG could be the first choice of treatment for scaphoid nonunion.

      Keywords

      Abbreviations:

      VBG (Vascularised bone graft), NVBG (Non-vascularised bone graft)

      Introduction

      Scaphoid fractures are sometimes overlooked because of their relatively subtle symptoms and peculiar shape, which in turn result in nonunion.

      Lee SK. Green's Operative Hand Surgery:7th ed. Vol 1: Elsevier Health Sciences, 2016.

      ,
      • Pinder RM
      • Brkljac M
      • Rix L
      • Muir L
      • Brewster M.
      Treatment of Scaphoid Nonunion: A Systematic Review of the Existing Evidence.
      Untreated scaphoid nonunion could progress to arthritic change, which is referred to as scaphoid nonunion advanced collapse wrist. Düppe et al. reviewed the 30-year follow-up results of scaphoid fractures treated with thumb spica short arm casts and found that 60% of the patients with nonunion showed radiocarpal osteoarthrosis and only 2% of those without nonunion demonstrated degenerative changes.
      • Düppe H
      • Johnell O
      • Lundborg G
      • Karlsson M
      • Redlund-Johnell I
      Long-term results of fracture of the scaphoid. A follow-up study of more than thirty years.
      Thus, a scaphoid nonunion should be treated surgically with internal fixation accompanied with bone graft to achieve bony union.

      Lee SK. Green's Operative Hand Surgery:7th ed. Vol 1: Elsevier Health Sciences, 2016.

      ,
      • Pinder RM
      • Brkljac M
      • Rix L
      • Muir L
      • Brewster M.
      Treatment of Scaphoid Nonunion: A Systematic Review of the Existing Evidence.
      ,
      • Ferguson DO
      • Shanbhag V
      • Hedley H
      • Reichert I
      • Lipscombe S
      • Davis TR.
      Scaphoid fracture non-union: a systematic review of surgical treatment using bone graft.
      ,
      • Karaismailoglu B
      • Guven MF
      • Erenler M
      • Botanlioglu H.
      The use of pedicled vascularized bone grafts in the treatment of scaphoid nonunion: clinical results, graft options and indications.
      However, the preferred donor site for bone grafting remains to be clearly established.
      • Pinder RM
      • Brkljac M
      • Rix L
      • Muir L
      • Brewster M.
      Treatment of Scaphoid Nonunion: A Systematic Review of the Existing Evidence.
      ,
      • Ferguson DO
      • Shanbhag V
      • Hedley H
      • Reichert I
      • Lipscombe S
      • Davis TR.
      Scaphoid fracture non-union: a systematic review of surgical treatment using bone graft.
      ,
      • Munk B
      • Larsen CF.
      Bone grafting the scaphoid nonunion - A systematic review of 147 publications including 5246 cases of scaphoid nonunion.
      ,
      • Severo AL
      • Lemos MB
      • Lech OLC
      • Barreto Filho D
      • Strack DP
      • Candido LK.
      Bone graft in the treatment of nonunion of the scaphoid with necrosis of the proximal pole: a literature review.
      For scaphoid nonunion treatment, there are three types of bone grafting techniques: conventional grafting, pedicled vascularised bone grafting (VBG), and free VBG. The VBG technique was initially considered an ideal technique and was expected to contribute to a 100% union rate; however, its union rate did not meet expectations. Chang et al., Hirche et al., and Straw et al. reported that the union rates of VBGs for scaphoid nonunion were at 75%, 50%, and 12%, respectively.
      • Chang MA
      • Bishop AT
      • Moran SL
      • Shin AY.
      The outcomes and complications of 1,2-intercompartmental supraretinacular artery pedicled vascularized bone grafting of scaphoid nonunions.
      • Hirche C
      • Heffinger C
      • Xiong L
      • et al.
      The 1,2-intercompartmental supraretinacular artery vascularized bone graft for scaphoid nonunion: management and clinical outcome.
      • Straw RG
      • Davis TR
      • Dias JJ.
      Scaphoid nonunion: treatment with a pedicled vascularized bone graft based on the 1,2 intercompartmental supraretinacular branch of the radial artery.
      Merrell et al. conducted a systematic review and meta-analysis and showed that the outcome of VBG is preferable to that of wedge grafting.
      • Merrell GA
      • Wolfe SW
      • Slade 3rd, JF
      Treatment of scaphoid nonunions: quantitative meta-analysis of the literature.
      However, they included not only comparative studies but also case series, and the analysis was a simple summation of the number of patients with bony union after VBG. Thus, the quality of the evidence was limited. Moreover, the latest findings in the subject area are not considered as the paper was published in 2002. Currently, the utility of VBG remains unknown. Hence, we hypothesised that VBG for scaphoid nonunion showed a superior union rate to non-vascularised bone grafts (NVBGs) and conducted a systematic review and meta-analysis to compare the union rate between VBG and NVBGs in patients with scaphoid nonunion.

      Materials and methods

      Search strategy

      Because we used the data extracted from officially published articles, the ethical committee in our hospital waived the need to obtain approval for this study. To manage its heterogeneity, we performed a manual systematic literature search for randomised controlled trials (RCTs) and comparative studies following a predefined protocol and in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist.
      • Moher D
      • Liberati A
      • Tetzlaff J
      • Altman DG.
      Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.
      Two authors independently reviewed the studies published between January 1, 1984, and September 31, 2020; the studies were from PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials. The search terms were as follows: ((scaphoid nonunion) OR (scaphoid pseudarthrosis)) AND (bone graft). Moreover, we conducted an electronic search of the databases on October 1, 2020. Table 1 presents the inclusion and exclusion criteria for the meta-analysis.
      Table 1Inclusion and exclusion criteria for article selection.
      Inclusion criteria
      • A full-length article with sufficient outcome data (i.e., sample size of each group for each result and/or ORs and SE, SD, or 95% CI) (minimum sample size requirement was 10) that can be used in the comparison between patients with scaphoid fracture nonunion treated with VBG and those treated with NVBG.

      • Studies including at least one patient who underwent VBG and one patient who had NVBG

      • Sample size >10.

      • Published between January 1, 1984, and September 30, 2020
      Exclusion criteria
      • If two studies based on the same topic were published by the same faculty, the older study was excluded.

      • Review articles, conference papers, or short letters

      • Studies focusing on patients in a specific category (adolescents, elderly adults, etc.)

      • More recent study dealing with the same patient group was published from the same facility
      VBG, vascularised bone graft; NVBG, non-vascularised bone graft; OR, odds ratio; SE, standard error; SD, standard deviation; CI, confidence interval.

      Data extraction

      Two investigators independently extracted the data from eligible studies using predetermined selection criteria. We planned to resolve discrepancies through a discussion with a third investigator; however, this was ultimately not necessary as there were no discrepancies. The studies were systematically assessed for quality and risk of bias by two independent researchers using the risk of a bias assessment tool for non-randomised controlled studies.
      • Kim SY
      • Park JE
      • Lee YJ
      • et al.
      Testing a tool for assessing the risk of bias for nonrandomized studies showed moderate reliability and promising validity.
      The study design data and patient characteristics, including the location of the fracture on the scaphoid, osteosynthesis techniques, mean follow-up period, mean age, and sex, were obtained from the selected articles. Furthermore, we identified the total number of bone graft techniques performed in the operation for scaphoid nonunion and the postoperative nonunion rate. We included the studies with a single bone graft technique for the treatment of nonunion. For multiple studies from the same facility with the same outcomes, we included only the most recent studies.

      Statistical analysis

      We calculated the odds ratios (ORs) for binary variables. Conventionally, a higher OR in the VBG cohort indicates a higher nonunion rate. For the primary outcome, we compared the nonunion rate between patients who received VBGs and those who received NVBGs using the data extracted from RCTs only. Additionally, we conducted the same analysis with the data extracted from not only RCTs but also other comparative studies. In the subgroup analysis, we compared the nonunion rate between pedicled VBG and NVBG and between free VBG and NVBG. To minimise the heterogeneity of outcome evaluation, we performed additional subgroup analysis with the studies that adopt outcome evaluation using computed tomography (CT) for all patients or patients suspected to be nonunion. We evaluated the results for heterogeneity using forest plot and I2 statistical tests and by comparing the summary ORs using random-effects models. We used funnel plots to evaluate publication bias. Regarding the sample size, we calculated the standard mean difference (Cohen's d).
      • Cohen J.
      All statistical analyses were performed with EZR version 1.54 (Saitama Medical Center, Jichi Medical University, Saitama, Japan), which is a graphical user interface for R (The R Foundation for Statistical Computing, Vienna, Austria).
      • Kanda Y.
      Investigation of the freely available easy-to-use software 'EZR' for medical statistics.
      EZR is a modified version of R commander that was designed to add statistical functions frequently used in biostatistics.

      Results

      Study selection

      Our search identified 1787 articles, from which 790 duplicate articles were excluded. Based on the inclusion and exclusion criteria, we performed an abstract search and a manuscript search. We identified 16 comparative studies, including 4 RCTs
      • Braga-Silva J
      • Peruchi FM
      • Moschen GM
      • Gehlen D
      • Padoin AV.
      A comparison of the use of distal radius vascularised bone graft and non-vascularised iliac crest bone graft in the treatment of non-union of scaphoid fractures.
      • Caporrino FA
      • Dos Santos JB
      • Penteado FT
      • de Moraes VY
      • Belloti JC
      • Faloppa F
      Dorsal vascularized grafting for scaphoid nonunion: a comparison of two surgical techniques.
      • Raju PK
      • Kini SG.
      Fixation techniques for non-union of the scaphoid.
      • Ribak S
      • Medina CE
      • Mattar Jr., R
      • Ulson HJ
      • Ulson HJ
      • Etchebehere M
      Treatment of scaphoid nonunion with vascularised and nonvascularised dorsal bone grafting from the distal radius.
      and 12 observational studies (Figure 1).
      • Aibinder WR
      • Wagner ER
      • Bishop AT
      • Shin AY.
      Bone Grafting for Scaphoid Nonunions: Is Free Vascularized Bone Grafting Superior for Scaphoid Nonunion?.
      • Ammori MB
      • Elvey M
      • Mahmoud SS
      • et al.
      The outcome of bone graft surgery for nonunion of fractures of the scaphoid.
      • Ciprian S
      • Iochum S
      • Kohlmann R
      • Dautel G
      • Dap F
      • Blum A
      MR imaging accuracy in the prediction of bone graft healing potential in scaphoid non-union.
      • Fox MG
      • Wang DT
      • Chhabra AB.
      Accuracy of enhanced and unenhanced MRI in diagnosing scaphoid proximal pole avascular necrosis and predicting surgical outcome.
      • Garcia RM
      • Leversedge FJ
      • Aldridge JM
      • Richard MJ
      • Ruch DS.
      Scaphoid nonunions treated with 2 headless compression screws and bone grafting.
      • Guzzini M
      • Lanzetti RM
      • Proietti L
      • Lupariello D
      • Iorio R
      • Ferretti A.
      The role of vascularized flaps in the treatment of proximal pole avascular necrosis in scaphoid non-unions.
      • Jaminet P
      • Götz M
      • Gonser P
      • Schaller HE
      • Lotter O.
      Treatment of Scaphoid Nonunion: Radiologic Outcome of 286 Patients in 10 Years.
      • Kömürcü M
      • Basbozkurt M
      • Gur E.
      Surgical treatment results in scaphoid nonunion.
      • Küntscher M
      • Tränkle M
      • Sauerbier M
      • Germann G
      • Bickert B.
      Management of proximal scaphoid bone pseudarthroses and fractures with the mini-Herbert screw via a dorsal approach.
      • Pechlaner S
      • Beck E.
      Reconstructive surgical procedures in scaphoid pseudarthrosis.
      • Schaller E
      • Lassner F
      • Pallua N
      • Schneider W
      • Berger A.
      A comparison of different treatment methods of pseudarthroses and recurrent pseudarthroses of the scaphoid.
      • Smeraglia F
      • Basso MA
      • Fonzone Caccese A
      • Bernasconi A
      • Mariconda M
      • Balato G
      Volar distal radius vascularized bone graft vs non-vascularized bone graft: a prospective comparative study.
      No arthroscopic-assisted bone grafts were included in this study.
      Figure 1
      Figure 1Flowchart of patient selection. We identified 997 studies in the electronic literature search. Based on the inclusion and exclusion criteria, we selected four randomised controlled trials and 12 observational studies for the meta-analysis.

      Study characteristics

      The characteristics of the patients in the articles included in the meta-analyses are shown in Table 2. Briefly, 89.0% of the patients were males (mean age, 26 years). Nonunion in the scaphoid waist accounted for 57% of the nonunion sites and that in the proximal pole for 36%.
      Table 2Detailed characteristics of the patients in the articles included in the meta-analyses.
      AuthorYearStudy designLocation of fractureOsteosynthesisMean follow-up periodMean ageSex (male/female)
      Aibinder et al.2019Retrospective studyWaist: 80, proximal pole: 38CS: 69, K-wire: 27, both: 1316.5 months2593/16
      Ammori et al.2019Retrospective studyWaist: 316, proximal pole: 119, distal pole: 27None: 4, K-wire: 35, CS: 422, other screw: 13–6 months: 179, 6–12 months: 149, 1–2 years: 91, 2 years: 4326427/33
      Braga-Silva et al.2008RCTWaist: 56, proximal pole: 24NVBG group HS: 45, VBG group wire: 30, HS: 52.8 years2656/24
      Caporrino et al.2014RCTWaist: 53, proximal pole: 10, others: 12All K-wire29.0 months2871/4
      Ciprian et al.2004Retrospective studyWaist: 4, proximal pole: 17Osteosynthesis pins (n=2)No description3118/3
      Fox et al.2015Retrospective studyProximal pole: 18No description14 CT cases: 96 days, 16 X-ray cases: 149 days1816/2
      Garcia et al.2014Retrospective studyWaist: 12, proximal pole: 5, distal pole: 2Trimed: 11, combined Acutrak Mini and Acutrak 2 Micro: 83.6 months for bony union2118/1
      Guzzini et al.2019Retrospective studyProximal pole necrosisNo description12.5 months3023/9
      Jaminet et al.2019Retrospective studyProximal 3rd: 126, middle 3rd: 130, distal 3rd: 30Mini-HS and/or K-wireNo description26258/28
      Kömürcü et al.2001Retrospective studyProximal: 6, middle: 20, distal: 16K-wire: 15, AO CS: 8, HS: 192.4 years2435/7
      Küntscher et al.2001Retrospective studyProximal poleK-wire and HS14.5 months2424/1
      Pechlaner et al.1990Retrospective studyNo descriptionK-wire (for VBG): 35, HS (for NVBG): 18>2 years27No description
      Raju et al.2011RCTProximal pole: 13, waist: 12, distal pole: 8 (including HS group)K-wire28 months2827/6 (including HS group)
      Ribak et al.2010RCTProximal pole: 37, middle: 47, distal pole: 2K-wire23.1 monthsNo descriptionNo description
      Schaller et al.1993Retrospective studyNo descriptionHS vs. Matti-Russe vs. VBGNo descriptionNo descriptionNo description
      Smeraglia et al.2020Prospective studyNo descriptionK-wire (for VBG): 9, HS (for NVBG): 12No description27All male
      HS, Herbert screw; CS, cannulated screw; VBG, vascularised bone graft; NVBG, non-vascularised bone graft; 1,2 ICSRA, 1,2 intercompartmental supraretinacular artery; MFC, medial femoral condyle.

      Meta-analysis outcomes

      In the primary analysis, which included RCTs only, we found no significant difference in nonunion rate between all VBGs and NVBG (summary OR, 0.54; 95% confidence interval [CI], 0.19–1.52) (Figure 2). Similar results were found in the secondary analysis, which included all comparative studies (summary OR, 0.71; 95% CI, 0.45–1.12) (Figure 3). These two analyses showed relatively low heterogeneities (I2 = 35% and 27%, respectively). No significant publication bias was detected in the two analyses (primary, p = 0.50; secondary, p = 0.45) (Figures 4 and 5). The outcomes of patients in each article are shown in Table 3. A total of 399 pedicled VBG, 68 free VBG, and 923 NVBG were performed, and the nonunion rates were 15%, 10%, and 18%, respectively. Pedicled VBGs were harvested from either the volar or dorsal radius, and most of the free VBGs were harvested from the medial femoral condyle. Neither pedicled VBG nor free VBG was superior to NVBG regarding nonunion rate (summary OR, 0.82; 95% CI, 0.56–1.20; and summary OR, 0.37; 95% CI, 0.07–1.87, respectively). In all selected articles, there were two studies (Jaminet, P. et al. 2019 and Smeraglia, F. et al.)
      • Jaminet P
      • Götz M
      • Gonser P
      • Schaller HE
      • Lotter O.
      Treatment of Scaphoid Nonunion: Radiologic Outcome of 286 Patients in 10 Years.
      ,
      • Smeraglia F
      • Basso MA
      • Fonzone Caccese A
      • Bernasconi A
      • Mariconda M
      • Balato G
      Volar distal radius vascularized bone graft vs non-vascularized bone graft: a prospective comparative study.
      that adopted CT outcome evaluation for all patients and three studies (Aibinder et al. 2019, Caporrino et al. 2014, and Küntscher et al. 2001)
      • Caporrino FA
      • Dos Santos JB
      • Penteado FT
      • de Moraes VY
      • Belloti JC
      • Faloppa F
      Dorsal vascularized grafting for scaphoid nonunion: a comparison of two surgical techniques.
      ,
      • Aibinder WR
      • Wagner ER
      • Bishop AT
      • Shin AY.
      Bone Grafting for Scaphoid Nonunions: Is Free Vascularized Bone Grafting Superior for Scaphoid Nonunion?.
      ,
      • Küntscher M
      • Tränkle M
      • Sauerbier M
      • Germann G
      • Bickert B.
      Management of proximal scaphoid bone pseudarthroses and fractures with the mini-Herbert screw via a dorsal approach.
      that adopted repeated CT outcome evaluation for patients who were suspected of nonunion. We performed subgroup analysis with these five articles, which resulted in similar results to the other outcomes (summary OR, 0.80; 95% CI, 0.55–1.59). Calculated Cohen's d for the meta-analysis of all studies, RCTs, and studies with CT outcome evaluation were 1, 0.83, and 1.00, respectively, which proved to be a sufficient sample size.
      Figure 2
      Figure 2Forest plot for the meta-analysis of randomised controlled trials. Non-vascularised bone graft was similar to vascularised bone graft. VBG, vascularised bone graft; NVBG, non-vascularised bone graft.
      Figure 3
      Figure 3Forest plot for the meta-analysis of comparative studies. Results of the meta-analysis of comparative studies were consistent with those of the meta-analysis of randomised controlled trials. VBG, vascularised bone graft; NVBG, non-vascularised bone graft.
      Figure 4
      Figure 4Funnel plot for the meta-analysis with randomised controlled trials. Significant publication bias was not found (p = 0.45).
      Figure 5
      Figure 5Funnel plot for the meta-analysis of all comparative studies. No significant publication bias was observed (p = 0.51).
      Table 3Techniques and outcomes of bone graft.
      AuthorYearPedicled VBG total numberPedicled VBG total nonunionType of pedicled VBGFree VBG total numberFree VBG nonunionType of free VBGNVBG total numberNVBG nonunionType of NVBG
      Aibinder et al.20193371,2-ICSRA455MFC: 45319Iliac crest bone graft
      Ammori et al.20198920Vascularized local bone flap62Free VBG: 629473Distal radius/ulna bone graft: 122, iliac crest: 172
      Braga-Silva et al.20083531,2-ICSRANANANA450Iliac crest
      Caporrino et al.20143541,2-ICSRANANANA408Distal radius NVBG
      Ciprian et al.200471From radiusNANANA143Iliac crest: 10, radius: 3, ulna: 1
      Fox et al.2015811,2-ICSRANANANA101Autogenous bone graft
      Garcia et al.201430Capsular-based vascularized distal radius graft20MFC: 2140Corticocancellous autograft from iliac crest
      Guzzini et al.2019NANANA150MFC: 15177Bone grafts
      Jaminet et al.20198213Palmar vascularized bone graftNANANA20417Iliac crest bone graft
      Kömürcü et al.200140Pronator quadratus pedicled Bone graftNANANA332Tricortical iliac crest
      Küntscher et al.200120RadiusNANANA233Cancellous bone graft: 19, interpositional iliac bone graft: 4
      Pechlaner et al.1990353Pechlaner-Hussl vascular Pedicle bone: transplantNANANA12224Matti-Russe I: 86, Russe II: 18, HS fixation: 18
      Raju et al.2011132Kuhlmann's VBGNANANA93Matti-Russe
      Ribak et al.2010465VBG from dorsal radiusNANANA4011Distal radius
      Schaller et al.199371VBG from dorsal radiusNANANA273Matti-Russe
      Smeraglia et al.202091Kuhlmann's VBGNANANA123Iliac bone graft
      Total39960687923164
      HS, Herbert screw; CS, cannulated screw; VBG, vascularized bone graft; 1,2 ICSRA, 1,2 intercompartmental supraretinacular artery; MFC, medial femoral condyle; NA, not applicable.

      Risk of bias

      The risk of bias is summarised in Table 4. Regarding participant selection, two studies included patients from different study periods,
      • Schaller E
      • Lassner F
      • Pallua N
      • Schneider W
      • Berger A.
      A comparison of different treatment methods of pseudarthroses and recurrent pseudarthroses of the scaphoid.
      ,
      • Smeraglia F
      • Basso MA
      • Fonzone Caccese A
      • Bernasconi A
      • Mariconda M
      • Balato G
      Volar distal radius vascularized bone graft vs non-vascularized bone graft: a prospective comparative study.
      and one study selected patients from a computer database.
      • Ciprian S
      • Iochum S
      • Kohlmann R
      • Dautel G
      • Dap F
      • Blum A
      MR imaging accuracy in the prediction of bone graft healing potential in scaphoid non-union.
      None of the studies controlled for confounding bias, and no performance bias was found. One study had a blinded outcome evaluation,
      • Garcia RM
      • Leversedge FJ
      • Aldridge JM
      • Richard MJ
      • Ruch DS.
      Scaphoid nonunions treated with 2 headless compression screws and bone grafting.
      and a musculoskeletal radiologist was involved in the outcome evaluation of one study.
      • Jaminet P
      • Götz M
      • Gonser P
      • Schaller HE
      • Lotter O.
      Treatment of Scaphoid Nonunion: Radiologic Outcome of 286 Patients in 10 Years.
      Six studies evaluated bony union with objective measurements using CT or magnetic resonance imaging. Outcome evaluation was performed using plain radiographs in four studies, and two studies did not mention their outcome evaluation strategy. Two studies excluded more than 20% of the study subjects because of incomplete outcome data,
      • Ammori MB
      • Elvey M
      • Mahmoud SS
      • et al.
      The outcome of bone graft surgery for nonunion of fractures of the scaphoid.
      ,
      • Ciprian S
      • Iochum S
      • Kohlmann R
      • Dautel G
      • Dap F
      • Blum A
      MR imaging accuracy in the prediction of bone graft healing potential in scaphoid non-union.
      and one study did not mention incomplete outcome data.
      • Pechlaner S
      • Beck E.
      Reconstructive surgical procedures in scaphoid pseudarthrosis.
      Although no studies referenced a published protocol with predefined outcomes, the expected outcomes were presented in all 12 observational studies.
      Table 4Risk of bias in the included non-randomized controlled studies (RoBANS).
      AuthorYearJournalStudy designSelection of participantsConfounding variablesMeasurement of exposureBlinding of outcome assessmentsIncomplete outcome dataSelective outcome reporting
      Aibinder et al.2019Hand (N Y)Retrospective studyLowHighLowLowLowLow
      Ammori et al.2019J Hand Surg Eur VolRetrospective studyLowHighLowHighHighLow
      Ciprian et al.2004J RadiolRetrospective studyHighHighLowLowHighLow
      Fox et al.2015Skeletal RadiolRetrospective studyLowHighLowHighLowLow
      Garcia et al.2014J Hand Surg AmRetrospective studyLowHighLowLowLowLow
      Guzzini et al.2019Acta BiomedRetrospective studyLowHighLow?LowLow
      Jaminet et al.2019EplastyRetrospective studyLowHighLowLowLowLow
      Kömürcü et al.2001J South Orthop AssocRetrospective studyLowHighLowHighLowLow
      Küntscher et al.2001UnfallchirurgRetrospective studyLowHighLowLowLowLow
      Pechlaner et al.1990UnfallchirurgRetrospective studyLowHighLowHigh?Low
      Schaller et al.1993Handchir Mikrochir Plast ChirRetrospective studyHighHighLow?LowLow
      Smeraglia et al.2020J Biol Regul Homeost AgentsProspective studyHighHighLowLowLowLow
      ?, unclear risk of bias.

      Discussion

      In this meta-analysis, a comparison of the union rates between VBG and NVBG was performed. In the analyses of both comparative studies and RCTs alone, VBG was not superior to NVBG. Free VBG showed the lowest nonunion rate among the bone graft procedures; however, the difference was not statistically significant.
      VBG for scaphoid nonunion was first performed by Roy-Camille in 1965; he applied a pedicled VBG from the palmar tubercle of the scaphoid to its nonunion site with an abductor pollicis brevis muscle pedicle.
      • Roy-Camille R.
      Fractures et pseudarthroses du scaphoide moyen.
      Currently, various VBG procedures using grafts harvested from the volar or dorsal aspect of the radius, second metacarpal base, medial femoral condyle, or iliac crest have been developed.
      • Doi K
      • Oda T
      • Soo-Heong T
      • Nanda V.
      Free vascularized bone graft for nonunion of the scaphoid.
      • Kuhlmann JN
      • Mimoun M
      • Boabighi A
      • Baux S.
      Vascularized bone graft pedicled on the volar carpal artery for non-union of the scaphoid.
      • Mathoulin C
      • Haerle M.
      Vascularized bone graft from the palmar carpal artery for treatment of scaphoid nonunion.
      • Pechlaner S
      • Hussl H
      • Kunzel KH.
      Alternative operative technique in scaphoid nonunion (prospective study).
      • Sawaizumi T
      • Nanno M
      • Ito H.
      Vascularized second metacarpal-base bone graft in scaphoid non-union by the palmar approach.
      • Sheetz KK
      • Bishop AT
      • Berger RA.
      The arterial blood supply of the distal radius and ulna and its potential use in vascularized pedicled bone grafts.
      • Zaidemberg C
      • Siebert JW
      • Angrigiani C.
      A new vascularized bone graft for scaphoid nonunion.
      They believed the efficacy of VBG for scaphoid nonunion, because of its peculiar vascularity pattern, first described by Gelberman in 1980, frequently caused avascular nonunion.
      • Gelberman RH
      • Menon J.
      The vascularity of the scaphoid bone.
      However, recent studies have reported contradictory outcomes.
      • Rancy SK
      • Swanstrom MM
      • DiCarlo EF
      • Sneag DB
      • Lee SK
      • Wolfe SW.
      Success of scaphoid nonunion surgery is independent of proximal pole vascularity.
      ,
      • Rancy SK
      • Schmidle G
      • Wolfe SW.
      Does Anyone Need a Vascularized Graft?.
      Rancy et al. have reported a case series of patients with scaphoid nonunion who underwent NVBG with Herbert screw fixation.
      • Rancy SK
      • Swanstrom MM
      • DiCarlo EF
      • Sneag DB
      • Lee SK
      • Wolfe SW.
      Success of scaphoid nonunion surgery is independent of proximal pole vascularity.
      They evaluated the vascularity of the proximal pole with preoperative magnetic resonance imaging, assessed intraoperative bleeding points, and performed histopathological analysis of the cancellous bone and concluded that proximal pole infarction is decidedly rare and that VBG is seldom required. Moreover, they reviewed the literature and summarised the systematic reviews, case series, and RCTs regarding VBG for scaphoid nonunion and cast doubt on the efficacy of VBG. 4232 Their conclusion was supported by our results, which included integrated data. In our study, we conducted meta-analyses of two different groups of studies, i.e., RCTs only and all comparative studies. As there were only four RCTs included, an additional meta-analysis including all comparative studies for the same topic was performed. Although several meta-analyses included four or fewer articles,
      • Cheng HT
      • Hsu YC
      • Wu CI.
      Does primary closure for dog bite wounds increase the incidence of wound infection? A meta-analysis of randomized controlled trials.
      • Head L
      • Gencarelli JR
      • Allen M
      • Boyd KU.
      Wrist ganglion treatment: systematic review and meta-analysis.
      • Metcalfe D
      • Aquilina AL
      • Hedley HM.
      Prophylactic antibiotics in open distal phalanx fractures: systematic review and meta-analysis.
      • van de Wall BJM
      • Ochen Y
      • Beeres FJP
      • et al.
      Conservative vs. operative treatment for humeral shaft fractures: a meta-analysis and systematic review of randomized clinical trials and observational studies.
      we believe that the number of articles included in a meta-analysis is essential.
      The results of the subgroup analyses indicated that both pedicled VBG and free VBG were not significantly superior to NVBG. Moreover, free VBG showed the lowest nonunion rate, and a few cases were treated with free VBG, which may explain the absence of a statistically significant difference. Further accumulation of cases may result in different conclusions.
      Although this study was conducted using a systematic protocol, a few limitations still existed. First, this study did not assess any patient-reported outcomes, functional outcomes, the duration from bone grafting to union, or radiographic parameters. Each study applied various types of measurement tools for these outcomes; thus, the analysis would have been difficult. In this study, we focused on the biological aspects of bone grafts for scaphoid nonunion. Second, we consolidated various types of VBGs. Data consolidation is a typical limitation of a meta-analysis as some of the specific data from the original sources may be lost. Nevertheless, a previous meta-analysis compared the efficacy of nine VBGs and concluded that no significant difference was found among the VBGs.
      • Ditsios K
      • Konstantinidis I
      • Agas K
      • Christodoulou A.
      Comparative meta-analysis on the various vascularized bone flaps used for the treatment of scaphoid nonunion.
      Third, we did not assess the type of osteosynthesis, which is automatically determined based on the fragment size or the used bone graft; thus, osteosynthesis cannot be an independent variable. Although several studies have reported that no specific fixation methods can contribute to an increased union rate,
      • Christodoulou LS
      • Kitsis CK
      • Chamberlain ST.
      Internal fixation of scaphoid non-union: a comparative study of three methods.
      ,
      • Hegazy G
      • Seddik M
      • Abd-Elghany T
      • et al.
      Treatment of unstable scaphoid waist nonunion with cancellous bone grafts and cannulated screw or Kirschner wire fixation.
      the lack of such an assessment may reduce the quality of this study. Fourth, the treatment methods varied depending on the type of fracture, especially in the non-randomised comparative studies. Fifth, we could not determine the uniformity of the part of the fracture because most of the selected studies did not report the detailed relationship between the nonunion rate, part of the fracture, and used techniques. Sixth, we did not evaluate the preoperative vascularity of the proximal fragment. Although this bias was managed by undertaking a meta-analysis of RCTs exclusively, it exists in the meta-analysis of all comparative studies and thus may influence the overall outcome.

      Conclusion

      Despite the limitations, we performed a thorough review of the literature and provided further information on the role of VBG in scaphoid nonunion treatment. Free VBG showed the lowest nonunion rate, and current evidence showed that VBG is not significantly superior to NVBG. Hence, the results of this study suggest that the efficacy of VBG should not be overestimated and that patients may benefit from treatment procedures that are not excessively invasive.

      Conflict of interest statement

      There are no conflicts of interest in the article.

      Acknowledgement

      We thank Editage (http://www.editage.com) for editing and reviewing this manuscript for the English language.

      Appendix. Supplementary materials

      References

      1. Lee SK. Green's Operative Hand Surgery:7th ed. Vol 1: Elsevier Health Sciences, 2016.

        • Pinder RM
        • Brkljac M
        • Rix L
        • Muir L
        • Brewster M.
        Treatment of Scaphoid Nonunion: A Systematic Review of the Existing Evidence.
        J Hand Surg Am. 2015; 40 (.e3): 1797-1805
        • Düppe H
        • Johnell O
        • Lundborg G
        • Karlsson M
        • Redlund-Johnell I
        Long-term results of fracture of the scaphoid. A follow-up study of more than thirty years.
        J Bone Joint Surg Am. 1994; 76: 249-252
        • Ferguson DO
        • Shanbhag V
        • Hedley H
        • Reichert I
        • Lipscombe S
        • Davis TR.
        Scaphoid fracture non-union: a systematic review of surgical treatment using bone graft.
        J Hand Surg Eur Vol. 2016; 41: 492-500
        • Karaismailoglu B
        • Guven MF
        • Erenler M
        • Botanlioglu H.
        The use of pedicled vascularized bone grafts in the treatment of scaphoid nonunion: clinical results, graft options and indications.
        FORT Open Rev. 2020; 5: 1-8
        • Munk B
        • Larsen CF.
        Bone grafting the scaphoid nonunion - A systematic review of 147 publications including 5246 cases of scaphoid nonunion.
        Acta Orthop Scand. 2004; 75: 618-629
        • Severo AL
        • Lemos MB
        • Lech OLC
        • Barreto Filho D
        • Strack DP
        • Candido LK.
        Bone graft in the treatment of nonunion of the scaphoid with necrosis of the proximal pole: a literature review.
        Rev Bras Ortop. 2017; 52: 638-643
        • Chang MA
        • Bishop AT
        • Moran SL
        • Shin AY.
        The outcomes and complications of 1,2-intercompartmental supraretinacular artery pedicled vascularized bone grafting of scaphoid nonunions.
        J Hand Surg Am. 2006; 31: 387-396
        • Hirche C
        • Heffinger C
        • Xiong L
        • et al.
        The 1,2-intercompartmental supraretinacular artery vascularized bone graft for scaphoid nonunion: management and clinical outcome.
        J Hand Surg Am. 2014; 39: 423-429
        • Straw RG
        • Davis TR
        • Dias JJ.
        Scaphoid nonunion: treatment with a pedicled vascularized bone graft based on the 1,2 intercompartmental supraretinacular branch of the radial artery.
        J Hand Surg Br. 2002; 27: 413
        • Merrell GA
        • Wolfe SW
        • Slade 3rd, JF
        Treatment of scaphoid nonunions: quantitative meta-analysis of the literature.
        J Hand Surg Am. 2002; 27: 685-691
        • Moher D
        • Liberati A
        • Tetzlaff J
        • Altman DG.
        Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.
        J Clin Epidemiol. 2009; 62: 1006-1012
        • Kim SY
        • Park JE
        • Lee YJ
        • et al.
        Testing a tool for assessing the risk of bias for nonrandomized studies showed moderate reliability and promising validity.
        J Clin Epidemiol. 2013; 66: 408-414
        • Cohen J.
        Statistical power analysis for the behavioral sciences. 1988; : 20-26
        • Kanda Y.
        Investigation of the freely available easy-to-use software 'EZR' for medical statistics.
        Bone marrow transplantation. 2013; 48: 452-458
        • Braga-Silva J
        • Peruchi FM
        • Moschen GM
        • Gehlen D
        • Padoin AV.
        A comparison of the use of distal radius vascularised bone graft and non-vascularised iliac crest bone graft in the treatment of non-union of scaphoid fractures.
        J Hand Surg Eur Vol. 2008; 33: 636-640
        • Caporrino FA
        • Dos Santos JB
        • Penteado FT
        • de Moraes VY
        • Belloti JC
        • Faloppa F
        Dorsal vascularized grafting for scaphoid nonunion: a comparison of two surgical techniques.
        J Orthop Trauma. 2014; 28: e44-e48
        • Raju PK
        • Kini SG.
        Fixation techniques for non-union of the scaphoid.
        J Orthop Surg (Hong Kong). 2011; 19: 80-84
        • Ribak S
        • Medina CE
        • Mattar Jr., R
        • Ulson HJ
        • Ulson HJ
        • Etchebehere M
        Treatment of scaphoid nonunion with vascularised and nonvascularised dorsal bone grafting from the distal radius.
        Int Orthop. 2010; 34: 683-688
        • Aibinder WR
        • Wagner ER
        • Bishop AT
        • Shin AY.
        Bone Grafting for Scaphoid Nonunions: Is Free Vascularized Bone Grafting Superior for Scaphoid Nonunion?.
        Hand (N Y). 2019; 14: 217-222
        • Ammori MB
        • Elvey M
        • Mahmoud SS
        • et al.
        The outcome of bone graft surgery for nonunion of fractures of the scaphoid.
        J Hand Surg Eur Vol. 2019; 44: 676-684
        • Ciprian S
        • Iochum S
        • Kohlmann R
        • Dautel G
        • Dap F
        • Blum A
        MR imaging accuracy in the prediction of bone graft healing potential in scaphoid non-union.
        Journal de radiologie. 2004; 85 (]): 1699-1706
        • Fox MG
        • Wang DT
        • Chhabra AB.
        Accuracy of enhanced and unenhanced MRI in diagnosing scaphoid proximal pole avascular necrosis and predicting surgical outcome.
        Skeletal Radiol. 2015; 44: 1671-1678
        • Garcia RM
        • Leversedge FJ
        • Aldridge JM
        • Richard MJ
        • Ruch DS.
        Scaphoid nonunions treated with 2 headless compression screws and bone grafting.
        J Hand Surg Am. 2014; 39: 1301-1307
        • Guzzini M
        • Lanzetti RM
        • Proietti L
        • Lupariello D
        • Iorio R
        • Ferretti A.
        The role of vascularized flaps in the treatment of proximal pole avascular necrosis in scaphoid non-unions.
        Acta Biomed. 2019; 90: 64-68
        • Jaminet P
        • Götz M
        • Gonser P
        • Schaller HE
        • Lotter O.
        Treatment of Scaphoid Nonunion: Radiologic Outcome of 286 Patients in 10 Years.
        Eplasty. 2019; 19: e5
        • Kömürcü M
        • Basbozkurt M
        • Gur E.
        Surgical treatment results in scaphoid nonunion.
        J South Orthop Assoc. 2001; 10: 215-220
        • Küntscher M
        • Tränkle M
        • Sauerbier M
        • Germann G
        • Bickert B.
        Management of proximal scaphoid bone pseudarthroses and fractures with the mini-Herbert screw via a dorsal approach.
        Unfallchirurg. 2001; 104 (]): 813-819
        • Pechlaner S
        • Beck E.
        Reconstructive surgical procedures in scaphoid pseudarthrosis.
        Unfallchirurg. 1990; 93 (]): 150-156
        • Schaller E
        • Lassner F
        • Pallua N
        • Schneider W
        • Berger A.
        A comparison of different treatment methods of pseudarthroses and recurrent pseudarthroses of the scaphoid.
        Handchir Mikrochir Plast Chir. 1993; 25 (]): 204-210
        • Smeraglia F
        • Basso MA
        • Fonzone Caccese A
        • Bernasconi A
        • Mariconda M
        • Balato G
        Volar distal radius vascularized bone graft vs non-vascularized bone graft: a prospective comparative study.
        J Biol Regul Homeost Agents. 2020; 34: 115-120
        • Roy-Camille R.
        Fractures et pseudarthroses du scaphoide moyen.
        Actual Chir Ortho R Poincare. 1965; 4 (Utilisation d'un greffo pedicule): 197-214
        • Doi K
        • Oda T
        • Soo-Heong T
        • Nanda V.
        Free vascularized bone graft for nonunion of the scaphoid.
        J Hand Surg Am. 2000; 25: 507-519
        • Kuhlmann JN
        • Mimoun M
        • Boabighi A
        • Baux S.
        Vascularized bone graft pedicled on the volar carpal artery for non-union of the scaphoid.
        J Hand Surg Br. 1987; 12: 203-210
        • Mathoulin C
        • Haerle M.
        Vascularized bone graft from the palmar carpal artery for treatment of scaphoid nonunion.
        J Hand Surg Br. 1998; 23: 318-323
        • Pechlaner S
        • Hussl H
        • Kunzel KH.
        Alternative operative technique in scaphoid nonunion (prospective study).
        Handchir Mikrochir Plast Chir. 1987; 19: 302-305
        • Sawaizumi T
        • Nanno M
        • Ito H.
        Vascularized second metacarpal-base bone graft in scaphoid non-union by the palmar approach.
        J Reconstr Microsurg. 2003; 19: 99-106
        • Sheetz KK
        • Bishop AT
        • Berger RA.
        The arterial blood supply of the distal radius and ulna and its potential use in vascularized pedicled bone grafts.
        J Hand Surg Am. 1995; 20: 902-914
        • Zaidemberg C
        • Siebert JW
        • Angrigiani C.
        A new vascularized bone graft for scaphoid nonunion.
        J Hand Surg Am. 1991; 16: 474-478
        • Gelberman RH
        • Menon J.
        The vascularity of the scaphoid bone.
        J Hand Surg Am. 1980; 5: 508-513
        • Rancy SK
        • Swanstrom MM
        • DiCarlo EF
        • Sneag DB
        • Lee SK
        • Wolfe SW.
        Success of scaphoid nonunion surgery is independent of proximal pole vascularity.
        J Hand Surg Eur Vol. 2018; 43: 32-40
        • Rancy SK
        • Schmidle G
        • Wolfe SW.
        Does Anyone Need a Vascularized Graft?.
        Hand Clin. 2019; 35: 323-344
        • Cheng HT
        • Hsu YC
        • Wu CI.
        Does primary closure for dog bite wounds increase the incidence of wound infection? A meta-analysis of randomized controlled trials.
        J Plast Reconstr Aesthet Surg. 2014; 67: 1448-1450
        • Head L
        • Gencarelli JR
        • Allen M
        • Boyd KU.
        Wrist ganglion treatment: systematic review and meta-analysis.
        J Hand Surg Am. 2015; 40 (.e8): 546-553
        • Metcalfe D
        • Aquilina AL
        • Hedley HM.
        Prophylactic antibiotics in open distal phalanx fractures: systematic review and meta-analysis.
        J Hand Surg Eur Vol. 2016; 41: 423-430
        • van de Wall BJM
        • Ochen Y
        • Beeres FJP
        • et al.
        Conservative vs. operative treatment for humeral shaft fractures: a meta-analysis and systematic review of randomized clinical trials and observational studies.
        J Shoulder Elbow Surg. 2020; 29: 1493-1504
        • Ditsios K
        • Konstantinidis I
        • Agas K
        • Christodoulou A.
        Comparative meta-analysis on the various vascularized bone flaps used for the treatment of scaphoid nonunion.
        J Orthop Res. 2017; 35: 1076-1085
        • Christodoulou LS
        • Kitsis CK
        • Chamberlain ST.
        Internal fixation of scaphoid non-union: a comparative study of three methods.
        Injury. 2001; 32: 625-630
        • Hegazy G
        • Seddik M
        • Abd-Elghany T
        • et al.
        Treatment of unstable scaphoid waist nonunion with cancellous bone grafts and cannulated screw or Kirschner wire fixation.
        J Plast Surg Hand Surg. 2021; 55: 167-172