Interventions for treating osteochondral defects of the talus in adults
Abstract
This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:
To determine the benefits and harms of the interventions used for treating osteochondral defects of the talus in adults. This will include comparisons of interventions in the following categories:
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Any intervention versus no intervention or placebo control;
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Different methods of non‐surgical treatment;
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Surgical versus non‐surgical treatment;
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Different methods of surgical treatment.
Background
Description of the condition
Osteochondral defects are areas of joint damage involving the articular hyaline cartilage and the underlying subchondral bone. These defects, also known as osteochondritis dissecans, can lead to osteoarthritis and cause serious disability. The defects or lesions are thought to be caused by an ischaemic event affecting the joint (Barrie 1987). Retrospective analysis has shown that the majority of patients with osteochondral defects have experienced previous ankle trauma (Canale 1978).
The ankle joint consists of three bones: the tibia (shin bone), the fibula (the other lower leg bone) and the talus (ankle bone). The talus, which lies above the calcaneus (heel bone), supports the weight of the body at the ankle. After an ankle sprain, patients often have unresolved ankle pain. Although locking of the ankle joint is rare, patients may experience clicking, grinding or functional instability at the ankle. A number of patients with a distracting (parts are pulled away from each other) foot or ankle injury also have an unrecognised osteochondral lesion (Alexander 1980).
Osteochondral defects of the talus occur predominantly on the talar dome, which is the uppermost part of the talus. The location of the defect is influenced by the mechanics of the injury. Berndt 1959 showed that an inverted ankle with a dorsiflexion force can cause a lateral (located on the outer portion) talar‐dome injury, while an inverted ankle with a plantar‐flexed force can cause a medial (located on the inner portion) talar‐dome injury. These authors also developed a system for classifying osteochondral defects using ankle radiographs. Osteochondral defects can involve: 1) an area of compressed cartilage and subchondral bone; 2) a partially detached osteochondral lesion; 3) a completely detached but not displaced osteochondral lesion; 4) a completely detached and displaced (i.e. free within the joint) osteochondral lesion. With the advent of magnetic resonance imaging (MRI), lesions can now be detected earlier and visualised more clearly.
Description of the intervention
The interventions for treating osteochondral defects of the talus can be categorised into non‐surgical and surgical. Non‐surgical interventions include activity restriction, physiotherapy and viscosity supplementation of the synovial fluid (the lubricating fluid within a joint) either by oral administration or intra‐articular injection.
Surgical interventions have focused on one of the following three management strategies (O'Driscoll 1998).
1. Removing the osteochondral loose body with or without stimulating fibrocartilage proliferation by subchondral microfracture, which is done by scraping (curettage) or drilling the joint surface.
2. Fixing the osteochondral loose body to the joint surface defect or filling the defect with a bone graft. This technique may improve the loading of forces across the lesion. If the osteochondral loose body can be repaired, the hyaline cartilage surface may be preserved.
3. Generating hyaline cartilage by replacing the defect with cartilage from another source. The replacement hyaline cartilage can be obtained from the patient (autogenous or autologous) or from another person (allogenic). The three techniques used to achieve this are autologous chondrocyte implantation (ACI), osteochondral autograft transfer grafts (OATS) and fresh allografts. In ACI, a small amount of cartilage is harvested from a non‐weight bearing joint surface. The component cells (chondrocytes) are then cultured in vitro to increase their number and implanted into the defect on a matrix or under a sutured tissue flap. In OATS, full thickness osteochondral plugs comprising sections of the joint surface, including cartilage and bone, are extracted from a joint area that has the least weight‐bearing load and transferred to the defect. A single plug that is cut to match the size of the defect or multiple small plugs can be inserted into the defect. The fresh allograft technique uses grafts taken from cadavers. However, unlike the other techniques, this has a risk of disease transmission.
How the intervention might work
The aim of treatment is to restore the joint surface to its original state. Activity restriction for acute injury may help to avoid further damage. Since articular cartilage has no blood supply, the essential substances required for tissue repair diffuse through the synovial fluid. One aim of physiotherapy is to move the nutrient rich synovial fluid throughout the joint. Viscosity supplementation, either indirectly by oral administration or directly by the intra‐articular injection of agents such as hyaluronic acid, is designed to augment the properties of the synovial fluid.
Because the repair process is unable to restore the original biomechanical properties of articular hyaline cartilage, an inferior type of cartilage, fibrocartilage, is produced instead. This has less resistance to shear forces and breaks down upon repeated loading. Osteochondral defects, by definition, are associated with the loss of normal bone structure beneath the damaged cartilage. Hence, there is an incongruity in the cartilage surface that alters the load distribution in the joint. Without restoration of the joint surface, osteoarthritis can develop (O'Driscoll 1998).
Why it is important to do this review
Osteochondral defects of the talus, although relatively rare, can be seriously disabling. There is continued controversy regarding the current methods of treatment. The aim of this review is to examine the evidence for the different interventions used to treat osteochondral defects of the talus in adults. An earlier non‐Cochrane review (Struijs 2001), published in German, found only non‐randomised controlled trials in a search for primary studies from 1966 to 2000. An updated review using the current criteria and methodology of The Cochrane Collaboration is needed.
Objectives
To determine the benefits and harms of the interventions used for treating osteochondral defects of the talus in adults. This will include comparisons of interventions in the following categories:
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Any intervention versus no intervention or placebo control;
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Different methods of non‐surgical treatment;
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Surgical versus non‐surgical treatment;
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Different methods of surgical treatment.
Methods
Criteria for considering studies for this review
Types of studies
All randomised controlled trials and quasi‐randomised controlled studies (the method used to allocate participants to a treatment is not strictly random, e.g. by date of birth, hospital record number or alternation) comparing interventions (including no treatment and placebo) for symptomatic defects of the talus will be included.
Types of participants
Adult participants (18 years of age or older) with symptomatic osteochondral lesions of the talus. The joint should be free from disease states, such as rheumatoid arthritis or osteoarthritis, as determined by radiographic evidence such as joint space narrowing, osteophyte formation, subchondral bony sclerosis or cyst formation.
Types of interventions
This review will compare surgical and non‐surgical interventions with surgical, non‐surgical or placebo interventions.The interventions will be reviewed individually and also as combined interventions when examined as such in trials.
Non‐surgical interventions include physiotherapy, bracing, activity restriction and intra‐articular viscosity supplementation. Trials testing pharmacological interventions, including oral viscosity supplementation, will be excluded.
Surgical interventions include loose‐body removal with or without microfracture by curettage or drilling; internal fixation of osteochondral lesions or filling of the defect with a bone graft; ACI; OATS with a single plug or mosaicplasty with multiple plugs; and fresh allografts. Trials comparing general surgical approaches, such as arthroscopy with open surgery, will be excluded.
Types of outcome measures
Primary outcomes
The primary outcomes will include pain, ankle function, treatment failure (unresolved symptoms or reoperation) and health‐related quality of life. Preference will be given to validated, patient‐reported outcome measures. The instruments commonly used to measure outcomes are:
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The American Orthopaedic Foot and Ankle Society score (Kitaoka 1994);
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The Short Form‐36 Health Survey (Ware 1992);
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The visual analogue pain scale (Revill 1976);
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The Ankle Osteoarthritis Scale (Domsic 1998).
Secondary outcomes
Functional outcomes
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Return to previous activities (work and sport)
Biological outcomes
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Hyaline cartilage development with a stable base as verified by second look arthroscopy or MRI
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Degenerative changes in the ankle
Adverse events
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Early and late complications such as infection
Search methods for identification of studies
Electronic searches
We will search the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register, the Cochrane Central Register of Controlled Trials (The Cochrane Library, current issue), MEDLINE (January 1950 to present), EMBASE (January 1988 to present) and CINAHL (January 1982 to present). We will also search Current Controlled Trials and the World Health Organization International Clinical Trials Registry for ongoing and recently completed trials. There will be no constraints on language or publication status. Abstracts will be included. In MEDLINE, the search strategy will be combined with the sensitivity‐ and precision‐maximising version of the Cochrane Highly Sensitive Search Strategy for identifying randomised controlled trials (Lefebvre 2008). Similar search strategies will be used for EMBASE and CINAHL. For details of all search strategies, see Appendix 1.
Searching other resources
We will look for additional studies by checking the bibliographies of trial reports and relevant review articles and searching locally available conference proceedings relevant to the topic area.
Data collection and analysis
Selection of studies
Records retrieved by the initial search will be reviewed to identify trials that meet the inclusion criteria. Full‐text articles will be retrieved and reviewed independently by the authors for the purpose of applying the inclusion criteria. Differences of opinion will be resolved by discussion among the authors.
Data extraction and management
Data from the studies will be extracted independently by a minimum of two authors using standardised forms. All differences of opinion between the authors will be resolved by discussion.
Assessment of risk of bias in included studies
Two of the authors will independently assess the risk of bias in the included studies using The Cochrane Collaboration's risk of bias tool (Higgins 2008). This tool assesses randomisation (sequence generation and allocation concealment), blinding (participants, personnel and outcome assessors), the completeness of outcome data, the selection of outcomes reported and other sources of bias. Other sources of bias include:
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selection bias ‐ we will assess the risk of bias from imbalances in key baseline characteristics (e.g. age, sex and symptom duration);
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performance bias ‐ we will assess the risk of bias from systematic differences in the care provided (e.g. surgeon or other care provider experience, rehabilitation weight‐bearing status);
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sponsorship bias ‐ we will assess the risk of bias from trial sponsorship.
Measures of treatment effect
Quantitative data reported in individual trials for outcomes listed in the inclusion criteria will be presented in the text and in the analyses using risk ratios with 95% confidence intervals (CIs) for dichotomous outcomes and mean differences with 95% CIs for continuous outcomes.
Unit of analysis issues
The unit of randomisation in the trials is usually the individual patient. If eligible cluster‐randomised trials are found, where the unit of randomisation is another entity, appropriate adjustments will be made before presenting the data. We will seek advice on the interpretation and presentation of the results from such trials from the statistical editors of the Cochrane Bone, Joint and Muscle Trauma Review Group.
Dealing with missing data
Where appropriate, we will perform intention‐to‐treat analyses to include all participants randomly assigned to the intervention groups. We will investigate the effect of dropouts and exclusions by conducting worse‐ and best‐case scenario analyses. We will be alert to the potential mislabelling or non‐identification of standard errors and standard deviations. We will not impute missing standard deviations in cases where they cannot be obtained from trial authors or derived from CIs or standard errors.
Assessment of heterogeneity
Heterogeneity will be assessed by visual inspection of the forest plot along with consideration of the test for heterogeneity and the I² statistic (Higgins 2003).
Assessment of reporting biases
If sufficient data are available we will assess publication bias by preparing a funnel plot.
Data synthesis
If considered appropriate, the results of comparable groups of trials will be pooled using the fixed‐effect model. The random‐effects model will be used when there is significant unexplained heterogeneity. Ninety‐five per cent confidence intervals will be used throughout.
Subgroup analysis and investigation of heterogeneity
Where possible, we will perform subgroup analyses to investigate the effects of patient age and sex and the duration and size of the osteochondral defect on outcomes for different treatment groups. We will use the technique described by Altman 2003 to test the statistical significance of any differences between the subgroups.
Sensitivity analysis
Where possible, we will conduct sensitivity analyses to examine the effects of various aspects of trial and review methodology, including missing data, study quality (specifically allocation concealment, outcome assessor blinding and reporting of surgical experience) and inclusion of trials only reported in abstracts, on the results. We will use the test of interaction to establish whether the differences between subgroups are statistically significant (Altman 2003).
