Background

Leg length discrepancies (LLDs) are a common phenomenon in the general community with 23% of the population having a discrepancy of 1 cm or more.1,2 The causes of LLDs can be subdivided into congenital disorders or acquired physeal disruption. Congenital LLDs include disorders such as hemihypertrophy/hemihyperplasia, skeletal dysplasia, developmental dysplasia of the hip, unilateral club foot and paralytic disorders, whereas acquired physeal disruption is commonly secondary to infection, trauma or tumors.2,3

Little functional impact is appreciated in LLDs of less than 2 cm,4 and small discrepancies may be considered "normal" given they are not linked with any specific pathology.5,6 Gait asymmetry or altered gait kinetics develops with an inequality of 2 cm or more,7-9 the larger the inequality the greater the mechanical disadvantage.9 If a LLD of greater than 2 cm is not addressed, the individuals have a greater propensity to develop back pain, structural scoliosis, equinus contracture of the ankle, osteoarthritis of the hip or knee and generally reduced quality of life.2,10,11

A number of different methods have been developed in an attempt to accurately predict the extent of LLDs at skeletal maturity. This is important for determining the most appropriate timing of an intervention as well as identifying the treatment best suited to the child. A discrepancy of less than 2 cm will very rarely require treatment and, if it does, conservative treatment with the aid of shoe raises should be sufficient.12 Children predicted to have a discrepancy of 2-5 cm at skeletal maturity are considered as candidates for epiphysiodesis.11-16 This cohort of patients is the population of interest for this systematic review. A discrepancy of greater than 5 cm is likely to require a limb lengthening procedure to correct the discrepancy.

All methods for predicting the extent of LLDs are required to make a number of assumptions such as:

* A girl's physis will fuse at the chronological age of 14 years.

* A boy's physis will fuse at the chronological age of 16 years.

* Each physis (for example distal femur and proximal tibia) has a constant rate of growth until maturity.2,17,18

Lee et al.19 in 2013 assessed the accuracy of current methods used to determine the timing of epiphysiodesis and reported that the most accurate one was the Original Green-Anderson growth remaining method.20 This protocol uses skeletal age to estimate the growth potential at the distal femur and proximal tibia; it is gender specific and mapped out over various skeletal ages. Other methods that were analyzed included the straight-line graph method described by Moseley,21 the multiplier method proposed by Paley et al.22,23 and the Modified Green-Anderson growth remaining model proposed by these authors. In general, they found that all methods generated an overcorrected value, leading to them making the conclusion that no method at present is accurate in predicting the final LLDs at maturity with surgery. However, all methods were clinically effective given there was a strong correlation between the expected and actual LLDs at maturity.

Little et al.17 evaluated the clinical accuracy of the Menelaus,24 Green-Anderson and the Moseley protocols. They identified that all carried a significant rate of undesirable outcomes, with 10-27% of outcomes being greater than 2 cm from the calculated predicted values. Little et al.17 proposed that this was because of the fact that none of these methods took into account qualitative factors often employed by clinicians, such as age of menarche, the presence of secondary sexual characteristics and parental and sibling heights. They concluded that it was inadvisable to recommend any surgical procedure based on a mathematical equation alone; however, all methods can be used to help guide timing with very similar accuracies.

Eastwood and Cole,25 in 1995, proposed the clinical graphic method for predicting LLDs that was based on Shapiro's26 idea that there are five different patterns of LLD. With this in mind they were able to modify the arithmetic method to match the growth pattern rather than assuming a constant annual increase in discrepancy. With this method, children were reviewed annually and as they approached the time for epiphysiodesis, appointments were increased to six monthly. Children underwent a single computed tomography (CT) scan at this point which confirmed any clinical measurements and determined the relative discrepancy of limb segments. This method was used to determine if femoral alone, tibial alone or combined epiphysiodesis was necessary to correct the deformity. Eastwood identified that using this method, the LLDs at maturity were consistently within 1 cm for all children. This method has not since been validated.

Epiphysiodesis is the process of surgically halting the growth of a long bone prematurely through manipulating its physis. It is a concept that was first described in 1933 by Phemister.27 It can be used to restrict the growth of part of a physis, which is of benefit in the management of angular deformities, or inhibit the growth of an entire physis when managing pure LLDs (shortening the longer limb). Some epiphysiodesis techniques permanently cease the growth of the physis, whereas other more recently developed techniques are able to transiently modulate the growth of that bone, which hypothetically results in greater control and flexibility for correcting LLDs.

The Phemister technique involves the excision of a 1-cm rectangular bone block of cortical bone containing the peripheral physis and adjacent meta-physeal and epiphyseal bone from the medial and lateral aspects of the physis. The physis is then curetted and the bone blocks reinserted after being rotated 180[degrees], thus creating a bone bridge bypassing the growth plate.27 This technique is open and results in permanent cessation of physeal growth. Since 1933, there have been multiple new techniques of epiphysiodesis proposed, most of which are percutaneous or minimally invasive.28 Compared with the Phemister technique, these MIE approaches have been shown to have similar efficacies with similar complication rates and shorter hospital stays and for these reasons the Phemister technique has become obselete.16,29-31 Therefore, this systematic review will focus on the effectiveness of MIE techniques, which are described below.

Canale and Christian,32 Ogilvie and King,33 and Timperlake et al.34 have focused on permanent percutaneous methods of MIE, using image intensification, under which the physis is ablated or destroyed with drills and curettes through small medial and lateral incisions. In 1998, Metaizeau et al.15 described a further permanent method of epiphysiodesis using two transphyseal screws obliquely placed across the physis forming a cross in both the coronal and sagittal planes.35 This concept is thought to work by applying compressive forces through the physis.

Blount and Clarke36 proposed the first reversible method of epiphysiodesis using three staples on each side of the physis. One staple spike would be placed in the metaphysis and the other in the epiphysis. There have been a number of reported complications with this form of reversible epiphysiodesis, including an unpredictable pattern of growth following the removal of staples, and the development of angular deformities.14,37 In 2007, Stevens38,39 introduced an alternative reversible technique, which relied on a tension band construct using eight-Plates. This concept was initially used for the correction of angular deformities but has since been modified to treat moderate LLDs. The use of eight-Plates for the correction of LLDs to date is quite controversial with Stewart et al.40 claiming they are not effective for epiphysiodesis about the knee. Their study found that the eight-Plates achieved suboptimal correction when compared with physeal ablation. However, following the publication of their study commentaries including that by Kaymaz and Komurcu41 have questioned the study's methodology. In the last few years there have been studies published looking at more experimental forms of epiphysiodesis such as radiofrequency ablation;42,43 however, due to the fact that these interventions remain in "experimental phases" they will not be included in this review.

The primary goal of all epiphysiodesis procedures is to reduce the disability associated with LLDs by reducing the discrepancy to less than 2 cm, thus eliminating or at least minimizing significant gait abnormalities and abnormal loading on joints. Unfortunately, like all surgical procedures, epiphysiodesis is not complication free. Recognized complications include articular effusions, postoperative hematomas, superficial wound infections, postoperative exostosis, iatrogenic fractures and failure to achieve growth arrest.2 A handful of studies have shown that the complication rates between open and MIE techniques are similar.4,39 However, comparative efficacy of different MIE methods such as transphyseal screws, drilling with curettage, eight-Plates and staples have been less well established. Independently, all four of these techniques of epiphysiodesis have been reported to yield low rates of complications and obtain satisfactory growth arrest.

The aim of this review is to assess whether one form of MIE is more effective than another in correcting moderate LLDs. Factors that will be evaluated include efficacy, complications, length of hospital stay, and reoperation rates. This review has the potential to identify complication profiles and provide a more sound understanding of the pros and cons of each method of MIE. A preliminary search of the JBI Database of Systematic Reviews and Implementation Reports, the Cochrane Library, CINAHL, PubMed and PROSPERO has revealed that there is currently no systematic review (either published or underway) on this topic.

Inclusion criteria

Types of participants

This review will consider studies that include:

* Children or adolescents with open physes. (It is likely only patients under the age of 16 will be included, though because of the variability in growing and physeal closure timing no participants will be excluded based on age.)

* Predicted LLD at skeletal maturity of between 2 cm and 5 cm.

Exclusion criteria:

* Predicted LLD at skeletal maturity of greater than 5 cm as MIE should not be first-line treatment option.

Types of intervention(s)

This review will consider studies that evaluate the use of different techniques for MIE. The specific techniques of interest include:

* Transphyseal screws

* Physeal drilling and curettage

* Physeal stapling

* Guided growth with eight-Plates.

The review will aim to compare the four listed interventions. Studies that have evaluated two or more of the interventions and studies that have investigated only a single intervention will be considered for inclusion.

Outcomes

This review will consider studies that include the following outcome measures:

Primary outcomes

* Absolute LLD (measured in centimeters) at skeletal maturity (methods of assessment may include, but will not be limited to, measurements taken from the anterior superior iliac spine to the medial malleolus, or through imaging modalities such as CT/plain films)

* Rate of correction

* Percentage of correction relative to desired correction

* Incidence of long-term complications such as:-Failure of growth plate arrest-Failure to achieve adequate reduction in LLD (<2 cm LLD)-Incidence of angular deformities-Hardware failure - such as breakage of physeal staples.

Secondary outcomes

* Incidence of acute complications such as:-Postoperative infection-Unplanned return to theatre-Hematomas/effusions large enough to impact of postoperative recovery

* Patient's ability to return to preoperative function, including:-Length of time taken for patient to return to school-Length of time taken for patient to return to sport-Knee range of motion

* Length of hospital stay.

* Overall quality of life measured using any validated scale.

Types of studies

Priority will be given to higher evidence-level study designs, first considering randomized controlled trials (RCTs). However, in the absence of RCTs, this review will consider both experimental and epidemiological study designs, including non-randomized controlled trials, quasi-experimental studies, before and after studies, prospective and retrospective cohort studies, case control studies and analytical cross-sectional studies for inclusion. This review will also consider descriptive epidemiological study designs, including case series and descriptive cross-sectional studies for inclusion. Individual case reports will be excluded, which will limit the inclusion of adverse events to those reported in larger studies rather than isolated cases.

Search strategy

The search strategy aims to find both published and unpublished studies. A three-step search strategy will be utilized in this review. An initial limited search of PubMed will be undertaken followed by analysis of the text words contained in the title and abstract, and the index terms used to describe articles. A second search using all identified keywords and index terms will then be undertaken across all included databases. Third, the reference list of all identified reports and articles will be searched for additional studies. All studies published in English, even those translated from a different primary language, will be considered for inclusion in this review. Articles published from 1998 onward will be considered for inclusion as this is when percutaneous transphyseal screws as a method of MIE was first used clinically.

The databases to be searched include:

* PubMed

* Embase

* Web of Knowledge

* Scopus.

Grey literature will be searched through the following sources:

* Scirus

* Mednar

* ProQuest Theses and Dissertations

* Grey Source

* Index to Theses

* Libraries Australia.

The following trial registries will also be searched:

* The Cochrane Central Register of Controlled Trials

* WHO ICTRP

* ClinicalTrials.gov

Papers presented at conferences or meetings hosted by State or National Orthopedic Associations, available through the relevant association website or on request, will also be considered for inclusion.

Initial keywords to be used will be:

"leg length inequality" [MH] OR "leg length discrepancy" [tw]

AND

Child [MH] OR pediatric [tw] OR paediatric [tw]

AND

Epiphysiodesis [tw] OR "transphyseal percutaneous screws" [tw] OR Metaizeau [tw] OR Canale [tw] OR Physeal drilling [tw] OR Blount [tw] OR "Transphyseal staples" [tw] OR "eight-Plate" [tw] OR "8-Plate" [tw] OR "Physeal manipulation" [tw] OR "tension band" [tw] OR (epiphyses [MH] AND (surgery [tw] OR surgical [tw]).

Assessment of methodological quality

Articles selected for retrieval will be assessed by two independent reviewers for methodological validity prior to inclusion in the review using standardized critical appraisal instruments from the Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument (JBI-MAStARI) (Appendix I). Any disagreements that arise between the reviewers will be resolved through discussion or with a third reviewer.

Data extraction

Data will be extracted from articles included in the review using the standardized data extraction tool from JBI-MAStARI (Appendix II). The data extracted will include specific details about the interventions, populations, study methods and outcomes of significance to the review question and specific objectives. The authors of the included studies will be contacted if important data that is relevant to the review is missing in the published articles.

Data synthesis

Quantitative data will, wherever possible, be pooled in statistical meta-analysis using JBI-MAStARI. All results will be subject to double data entry. Effect sizes expressed as odds ratio (for categorical data) and weighted mean differences (for continuous data) and their 95% confidence intervals will be calculated for analysis. Heterogeneity will be statistically assessed using the standard [chi]² and also explored using subgroup analyses based on the different study designs included in this review. Depending on the available data additional subgroup analyses may be performed, such as subgroup analyses based on different patient demographics or timing of the MIE procedure. Where statistical pooling is not possible the findings will be presented in narrative form, including tables and figures to aid in data presentation, wherever appropriate.

Acknowledgements

This systematic review forms partial submission for the degree award of Master of Clinical Science for the first author.

Appendix I: Appraisal instruments

MAStARI appraisal instrument

Appendix II: Data extraction instruments

MAStARI data extraction instrument

References