Secondary bone grafting for alveolar cleft in children with cleft lip or cleft lip and palate
Abstract
This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:
To compare the effectiveness of different secondary bone grafting methods (timing, technique, source of graft).
Background
Description of the condition
Alveolar cleft (osseous defect in the alveolus) is a common congenital anomaly which affects approximately 75% of the cleft lip or cleft lip and palate patients. The aetiology of this clefting is still poorly understood, but it is most likely considered to be multifactorial involving genetic and environmental factors (Malcolm 1990). The alveolar cleft may affect the developing dentition and contribute to the collapse of the alveolar segments. Failure to reconstruct the alveolar cleft may give rise to problems including oronasal fistula, fluid reflux, speech pathology, anteroposterior and transverse deficiency of the maxilla, lack of bone support for the anterior teeth, dental crowding, and facial asymmetry (Waite 1996). Patients with a bony defect in the alveolar process with a symptomatic oronasal fistula and/or a lack of bone impairing tooth eruption or orthodontic treatment or prosthodontic rehabilitation in this area, should be considered for alveolar bone grafting (Enemark 1985).
Description of the intervention
Bone grafting of the alveolus is now generally acknowledged to be as integral to the management of the cleft patient as that of the primary lip or palate repair (Cohen 1993). Before the 1970s, primary alveolar bone grafting was commonly carried out until its adverse developmental effects on maxillary growth, severe crossbites, and poor alveolar morphology with unerupted or unsupported teeth were emphasized by Koberg (Koberg 1973) and Ross (Ross 1987). Early secondary bone grafting results in improved orofacial development but is often not ideal (Johanson 1961). Since the reports describing secondary alveolar bone grafting by Boyne and Sands (Boyne 1972), this procedure has become the common method of choice (Turvey 1984; Bergland 1986; Newlands 2000; Hynes 2003).
The optimal timing of bone graft placement remains controversial. Boyne and Sands (Boyne 1976) have used chronological nomenclature in alveolar bone grafting to avoid confusion in this concept: 1) Primary bone grafting: when bone grafting is performed in children younger than 2 years of age; 2) early secondary bone grafting: to be applied in patients between 2 and 5 years old; and 3) secondary bone grafting: when procedures are undertaken in patients greater than 5 years of age.
How the intervention might work
The general steps for secondary alveolar bone grafting are as follows. Firstly, mucoperiosteal flaps are made on the palate and vestibular surfaces of the maxillary segments to widely expose the alveolar bony defect. Meanwhile, the graft materials either autogenous bone or bone substitute are prepared or harvested. The nasal mucosa is firstly closed to repair the nasal floor. It is then pushed upwards and the bony wall is exposed. Bone or bone substitute is then packed into the defect, filling the alveolar defect completely. The palatal flaps are then released for primary closure of the oral layer. Often a finger flap is utilised from the vestibule and rotated over the alveolus. Lastly, all the flaps are sutured together to close the oral layer over the graft in the cleft site (Bergland 1986).
Secondary alveolar bone grafting may bring clefting patients several benefits. (1) It gives bony support to the teeth proximal to the cleft and greatly enhances the follow‐up orthodontic treatment (Waite 1980; Bertz 1981; Turvey 1984). (2) It gives a bony base for eruption of teeth in the line of the cleft and this prevents drifting of proximal teeth into the cleft and their premature loss (Boyne 1972; Jolleys 1972; Turvey 1984). (3) It provides union to the maxillary arch and re‐establishes alveolar bone contour (Skoog 1967; Pickrell 1968; Boyne 1972; Turvey 1984; Enemark 1985). (4) It provides support to arch width and minimizes collapse of the maxillary arch (Pickrell 1968; Epstein 1970; Bertz 1981). (5) It stabilizes the maxillary segments for the maintenance of the dentition and mastication (Skoog 1967; Pickrell 1968; Waite 1980; Turvey 1984; Enemark 1985; Bergland 1986). (6) It reduces notching of the alveolar ridge (Bergland 1986). (7) It eliminates oronasal fistulae to improve the oral hygiene (Pickrell 1968; Boyne 1972; Waite 1980; Bertz 1981; Turvey 1984; Enemark 1985). (8) It may improve facial appearance through restoring facial symmetry, providing alar base support, and establishing nasolabial contour (Pickrell 1968; Waite 1980; Bertz 1981; Turvey 1984). (9) It may provide the patient with the feeling of normalcy in a very serious oral facial defect and improve function and aesthetics, and contribute to personality, confidence, and social acceptance.
Secondary alveolar bone grafting may cause (1) increased incidence of canine impaction (Bergland 1986; McCanny 1998; Trindade 2005); (2) donor site morbidity (Hughes 2002; Swan 2006); (3) reduced anterior‐posterior and/or vertical maxillary growth (Ross 1987; Trotman 1997; Levitt 1999).
Why it is important to do this review
Although secondary alveolar bone grafting has been widely accepted by professionals within cleft care, there is still controversy as to (i) the age at which secondary bone grafting should be performed (Bergland 1986), (ii) the type of bone graft and the site from which the donor bone will be harvested (Freihofer 1993), and (iii) whether orthodontic treatment prior to grafting influences outcome (Long 1995; Kindelan 1999). Furthermore, the Clinical Standards Advisory Group (CSAG) reported that only 58% of children had a successful graft in the UK (Sandy 1998). A number of patients with alveolar cleft had an unsuccessful first bone graft or were not grafted at the optimal age (Williams 2001).
Poor outcome and the existing controversies of secondary bone grafting indicate that there is a need to evaluate the existing evidence for this procedure and identify best practice and further areas for good quality primary research.
Objectives
To compare the effectiveness of different secondary bone grafting methods (timing, technique, source of graft).
Methods
Criteria for considering studies for this review
Types of studies
Only randomised controlled clinical trials (RCTs) will be included.
Types of participants
Inclusion criteria
(1) Patients with the diagnosis of, cleft lip and alveolar process only, unilateral cleft lip and palate and bilateral cleft lip and palate involving the alveolar process. This would include complete or incomplete alveolar cleft types and cleft types involving simonarts bands.
(2) Patients greater than 5 years of age.
Exclusion criteria
(1) Edentulous premaxilla.
(2) Atypical or non‐described cleft diagnoses.
(3) With associated syndromic conditions.
Types of interventions
Any form of secondary alveolar bone grafting: when this operation is undertaken in patients greater than 5 years of age.
Comparisons may include variations in timing, techniques, donor sites and bone substitutes.
Types of outcome measures
Primary outcomes
Retention of graft ‐ oral and nasal levels:
1. clinical assessment: e.g. closure of the oral nasal fistulae, insertion of an implant or integration of denture;
2. radiographic assessment: e.g. bony fill in the grafted area including interalveolar septum height/width, height of nasal floor support for alar base, etc..
Secondary outcomes
1. Tooth eruption.
2. Gingival health.
3. Surgical complications.
4. Alar base support.
Search methods for identification of studies
Electronic searches
The following electronic databases will be searched: the Cochrane Oral Health Group's Trials Register (to present), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library current issue), MEDLINE (1950 to present), and EMBASE (1980 to present).
For the identification of the potential studies included or considered for this review, detailed search strategies will be developed for each database to be searched. These will be based on the search strategy developed for MEDLINE (Appendix 1) but revised appropriately for each database. The MEDLINE search strategy will be combined with the Cochrane Highly Sensitive Search Strategy (CHSSS) for identifying randomised trials in MEDLINE: sensitivity maximising version (2008 revision) as published in box 6.4.c of the Cochrane Handbook for Systematic Reviews of Interventions version 5.0.1 (updated September 2008) (Higgins 2008).
There will be no restriction with regard to publication language.
Searching other resources
Conference proceedings and abstracts will be searched. A search of the Internet will be also undertaken. Manufacturers and first authors of trial reports will be contacted in an attempt to identify any unpublished or ongoing clinical trials and to clarify data as necessary. Reference lists of included studies will be screened for further trials. We will not handsearch any specific journals but examine the reference lists of potential clinical trials and the review authors' personal database of trial reports in an attempt to identify any additional studies or those not identified in the searches. We will also contact experts in the field and request information on unpublished and ongoing trials.
Data collection and analysis
Selection of studies
The abstracts of studies resulting from the searches will be independently assessed by two review authors (Jing Guo (JG) and Qifeng Zhang (QZ)) and all irrelevant studies will be excluded. Full copies of all relevant and potentially relevant studies, those appearing to meet the inclusion criteria, or for which there are insufficient data in the title and abstract to make a clear decision, will be obtained. The full text copies will be assessed independently by these two review authors and any disagreement on the eligibility of included studies will be resolved through discussion. Studies not matching the inclusion criteria will be excluded and eliminated from further review and their details and reasons for their exclusion will be noted in the 'Characteristics of excluded studies' table in Review Manager (RevMan) 5.
Data extraction and management
Review authors will screen titles and abstracts of publications obtained by the search strategy. When the study fulfils the inclusion criteria, data concerning methodological issues, characteristics of participants, interventions and outcome measures will be independently extracted using a standard extraction form. The review authors will not be blinded to author, institution and journal of publication of results.
We will extract the following details.
(1) Study methods: method of allocation, masking of participants and outcome assessors, exclusion of participants after randomisation and proportion of follow‐up losses.
(2) Participants: country of origin, sample size, demographic characteristics, inclusion and exclusion criteria as described in the criteria for considering studies for this review.
(3) Intervention: any form of secondary alveolar bone grafting. Variations in timing, techniques, donor sites and bone substitutes.
(4) Outcomes: primary and secondary outcomes as described in the outcome measures section of this review.
If stated, the sources of funding of any of the included studies will be recorded. This information will be used to help with evaluation of the clinical homogeneity and the external validity of any included trials.
A 'Summary of findings table' will be made using GRADEprofiler software and included in the review.
Assessment of risk of bias in included studies
In order to ensure that variation was not caused by systematic errors in the design of study, two review authors (JG, QZ) will independently grade the selected trials and every trial will be assessed following the domain‐based evaluation described in the Cochrane Handbook for Systematic Reviews of Interventions 5.0.1 (Higgins 2008). The evaluations will be compared and any inconsistencies between the review authors in the interpretation of inclusion criteria and their significance to the selected trials will be discussed and resolved.
The following domains will be assessed as 'Yes' (i.e. low risk of bias), 'Unclear' (uncertain risk of bias) or 'No' (i.e. high risk of bias). The study author(s) will be contacted to seek clarification in case of uncertainty over data:
(1) Sequence generation
(2) Allocation concealment
(3) Blinding (of participants, personnel and outcome assessors)
(4) Incomplete outcome data
(5) Selective outcome reporting
(6) Other sources of bias.
These assessments will be reported for each individual study in the 'Risk of bias' table under the 'Characteristics of included studies'.
Measures of treatment effect
Dichotomous data
For dichotomous data, risk ratios (RR) and 95% confidence intervals (CI) will be estimated according to the intention‐to‐treat principles. For dichotomous outcomes, the weighted absolute risk difference will be calculated using the risk difference (RD) statistic in RevMan. RR‐1 calculates the weighted relative percent change (Schünemann 2008). The number needed to treat (NNT) will be calculated from the control group event rate (unless the population event rate is known) and the risk ratio using the Visual Rx NNT calculator (Cates 2008). They will be presented in the results as well as in the 'Summary of findings table'.
Continuous data
Continuous outcomes will be pooled as weighted mean differences (WMD), when trials using the same scale are pooled. For continuous outcomes pooled on different scales, the standardized mean difference (SMD) will be used. Continuous data will be presented as 'endpoint' or 'change from baseline', depending on the availability of data from primary studies (Schünemann 2008). We will also make available the 95% CI around the estimate effects.
Independently of whether continuous or dichotomous, the fixed‐effect model will be preferred for pooled data, but the random‐effects model will be used when heterogeneity is present.
Unit of analysis issues
The analysis of studies with non‐standard designs will be considered whether in each study:
• Groups of individuals were randomised together to the same intervention (e.g. cluster‐randomised trials)
• Individuals undergo more than one intervention (e.g. in a cross‐over trial, or simultaneous treatment of multiple sites on each individual)
• There are multiple observations for the same outcome (e.g. repeated measurements, recurring events, measurements on different body parts).
Dealing with missing data
For missing data (for example, publication bias, outcome not measured, lack of intention‐to‐treat analysis, attrition from the study) the following strategies will be adopted:
• Whenever possible, contact the original investigators to request missing data
• Make explicit the assumptions of any methods used to cope with missing data: for example, that the data are assumed missing at random, or that missing values were assumed to have a particular value such as a poor outcome
• Perform sensitivity analyses to assess how sensitive results are to reasonable changes in the assumptions that are made
• Address the potential impact of missing data on the findings of the review in the 'Discussion' section.
Assessment of heterogeneity
Heterogeneity will be assessed using the Chi2 test in conjunction with the I2 statistic. A useful statistic for quantifying inconsistency is I2 = [(Q ‐ df )/Q] x 100%, where Q is the Chi2 statistic and df is its degrees of freedom. Significance for the Chi2 test will be set at P < 0.10 due to the low power of this test (Deeks 2008). Substantial heterogeneity will be considered if the I2 statistic shows a value greater than 50%. When significant heterogeneity is present, an attempt will be made to explain the differences based on the clinical characteristics of the included studies.
Assessment of reporting biases
To assess publication bias, data will be plotted on a funnel graph in RevMan.
Data synthesis
In the absence of significant heterogeneity, a fixed‐effect model will be used. However, if significant heterogeneity is demonstrated, a random‐effects model will be used for analysis. Where available, the analyses will be based on intention‐to‐treat data from the individual studies. The data from included trials will be combined in a meta‐analysis if they are sufficiently homogeneous, both clinically and statistically.
Subgroup analysis and investigation of heterogeneity
Subgroup analyses will be conducted to explore the influence of study characteristics such as the types of cleft, size of cleft, orthodontic history, technique and source of bone for transplant on the meta‐analysis outcome. Heterogeneity in the studies results will be appreciated by examining forest plot graphs and by calculating formal tests of homogeneity as I2 statistics.
Sensitivity analysis
Sensitivity analyses will be used to assess all included studies, in relation to the different levels of methodological quality (e.g. 'yes' or 'no', meaning 'low risk of bias' and 'high risk of bias', respectively), and clinical heterogeneity (Deeks 2008).
