Interventions for treating osteochondral defects of the talus in adults

Abstract

Background

Osteochondral defects of the talus are usually a consequence of trauma. They can cause chronic pain and serious disability. Various interventions, non‐surgical and surgical, have been used for treating these defects.

Objectives

The objective of this review is to determine the benefits and harms of the interventions used for treating osteochondral defects of the talus in adults.

Search methods

We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register, the Cochrane Central Register of Controlled Trials, MEDLINE, MEDLINE In‐Process, EMBASE, Current Controlled Trials, the WHO International Clinical Trials Registry Platform and reference lists of articles. Date of last search: December 2009.

Selection criteria

Eligible for inclusion were any randomised or quasi‐randomised controlled clinical trials evaluating interventions for treating osteochondral defects of the talus in adults. Our primary outcomes included pain, ankle function, treatment failure (unresolved symptoms or reoperation) and health‐related quality of life. Preference was given to validated, patient‐reported outcome measures.

Data collection and analysis

Two review authors independently evaluated trials for inclusion and, for the included trial, independently assessed the risk of bias and extracted data.

Main results

One small trial with 15 participants and six months follow‐up was included. This trial was published only as a conference abstract, which provided inadequate information to judge the trial's methods and no numerical results. The trial reported that a series of three intra‐articular hyaluronan injections started three weeks after arthroscopic microfracture did not to improve pain but may have improved one aspect of mobility. There were no available data to check this claim.

Authors' conclusions

There is insufficient evidence from randomised trials to determine which interventions are best for osteochondral defects of the talus in adults. High quality randomised trials are required to guide non‐surgical and surgical treatment decisions for these injuries.

Plain language summary

Interventions for treating defects of the joint surfaces of the ankle bone in adults

Osteochondral defects are limited areas of damage to the lining of a joint. These defects involve the joint surface (chondral) and also the bone underneath the surface (osteo). The ankle is composed of three bones named the tibia (shin bone), fibula (the other lower leg bone) and talus (ankle bone). This review just looks osteochondral defects in the talus. Such defects occur mainly after trauma. They are rare but can result in pain and significant disability.

Treatment can be either by non‐surgical or surgical means. Non‐surgical interventions include activity restriction, physiotherapy and supplementation of the synovial fluid (the lubricating fluid within a joint). Surgical interventions by keyhole or open surgery aim to regenerate or replace the articular surface of the joint. This review included only one very small randomised trial with 15 participants, all of whom had chronic pain from osteochondral defects in the ankle bone. This trial looked at the effect of injecting hyaluronic acid, a lubricant, into the joint three weeks after surgical repair. However, there was only a brief report of this small and probably biased trial. There were no numerical data to draw conclusions on the effects of the intervention.

Currently there is insufficient evidence from randomised trials to determine which interventions are best for osteochondral defects of the talus in adults.

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 1980).

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. 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. Hepple 1999 developed an MRI‐based classification which included the presence of oedema or cysts within the subchondral bone. Theoretically, oedema (swelling) indicates an acute injury that is more likely to heal whereas cysts indicate a chronic injury that is unlikely to heal.

Patients with an osteochondral defect often have unresolved ankle pain. They may experience clicking, grinding or functional instability at the ankle. Locking of the ankle joint is rare.

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. This review provides an update of the evidence, using the current criteria and methodology of The Cochrane Collaboration.

Objectives

To determine the benefits and harms of the interventions used for treating osteochondral defects of the talus in adults. This following comparisons of interventions were set out for inclusion:

• Any intervention versus no intervention or placebo control;

• Different methods of non‐surgical treatment;

• Surgical versus non‐surgical treatment;

• Different methods of surgical treatment.

Methods

Criteria for considering studies for this review

Types of studies

We included any 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.

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 set out to compare surgical and non‐surgical interventions with surgical, non‐surgical or placebo interventions.We stipulated that the interventions would 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, were 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. We stipulated that trials comparing general surgical approaches, such as arthroscopy with open surgery, would be excluded.

Types of outcome measures

Primary outcomes

We stated that the primary outcomes would include pain, ankle function, treatment failure (unresolved symptoms or reoperation) and health‐related quality of life. Also, that preference would be given to validated, patient‐reported outcome measures. The instruments commonly used to measure outcomes are:

• The American Orthopaedic Foot and Ankle Society score (Kitaoka 1994);

• The Short Form‐36 Health Survey (Ware 1992);

• The visual analogue pain scale (Revill 1976);

• The Ankle Osteoarthritis Scale (Domsic 1998).

Secondary outcomes

Functional outcomes

• Return to previous activities (work and sport)

Biological outcomes

• Hyaline cartilage development with a stable base as verified by second look arthroscopy or MRI (magnetic resonance imaging)

• Degenerative changes in the ankle

Adverse events

• Early and late complications such as infection

Search methods for identification of studies

Electronic searches

We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (22 December 2009), the Cochrane Central Register of Controlled Trials (The Cochrane Library 2009, Issue 4), MEDLINE (1950 to November week 3 2009), MEDLINE In‐Process (December 2009), and EMBASE (1988 to December 2009).

In MEDLINE, the subject‐specific search strategy was combined with the sensitivity‐maximising version of the Cochrane Highly Sensitive Search Strategy for identifying randomised controlled trials (Lefebvre 2009), and modified for use in other databases. SeeAppendix 1 for all search strategies. There were no constraints based on language or publication status.

We also searched Current Controlled Trials and the WHO International Clinical Trials Registry Platform for ongoing and recently completed trials (28 December 2009).

Searching other resources

Authors of relevant studies were contacted by email requesting information on unpublished data and ongoing studies. Bibliographies of recent review papers and all relevant included, excluded and ongoing studies were searched to identify other potentially suitable studies.

Data collection and analysis

Selection of studies

Records retrieved by the initial search were reviewed to identify trials that met the inclusion criteria. Full‐text articles were retrieved and reviewed independently by the authors for inclusion. Where necessary, trial authors were contacted for clarification on trial methodology and advice sought from editorial staff of the Cochrane Bone, Joint and Muscle Trauma Group. Differences of opinion were resolved by discussion among the authors.

Data extraction and management

Data from the studies were extracted independently by two authors using standardised forms. All differences of opinion between the authors was resolved by discussion.

Assessment of risk of bias in included studies

Two of the authors independently assessed 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 assessed were:

• selection bias resulting from major imbalances in key baseline characteristics (e.g. age, sex and symptom duration);

• performance bias resulting from systematic differences in the care provided (e.g. surgeon or other care provider experience, rehabilitation weight‐bearing status);

• sponsorship bias from potential conflict of interest from trial sponsors.

Measures of treatment effect

If possible, we planned to report quantitative data reported in individual trials for outcomes listed in the inclusion criteria 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 had been found, where the unit of randomisation is another entity, appropriate adjustments would have been made before presenting the data.

Dealing with missing data

Where appropriate, we planned to perform intention‐to‐treat analyses to include all participants randomly assigned to the intervention groups. Additionally, we stipulated that we would investigate the effect of dropouts and exclusions by conducting worst‐ and best‐case scenario analyses. We would have been alert to the potential mislabelling or non‐identification of standard errors and standard deviations. We stated that we would not impute missing standard deviations in cases where they could not be obtained from trial authors or derived from CIs or standard errors.

Assessment of heterogeneity

We specified a priori that heterogeneity would 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

There were insufficient data to assess publication bias by preparing a funnel plot.

Data synthesis

If considered appropriate, the results of comparable groups of trials would have been pooled using the fixed‐effect model. The random‐effects model would have been used when there was significant unexplained heterogeneity. Ninety‐five per cent confidence intervals were intended throughout.

Subgroup analysis and investigation of heterogeneity

We specified in our protocol our plans for 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 would have used the technique described by Altman 2003 to test the statistical significance of any differences between the subgroups.

Sensitivity analysis

Where possible, we planned to 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.

Results

Description of studies

Results of the search

The Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (22 December 2009) search produced eight reports of which five focused on the management of osteochondral defects of the talus. After study selection, including receiving additional clarification on methods from a trial author, one trial was included (Bilge 2009), three were excluded (Gobbi 2006; Koulalis 2009; Takao 2004) and one is an ongoing trial with a published protocol (van Bergen 2009).

The results of our searches of other databases are described below.

• Cochrane Central Register of Controlled Trials (The Cochrane Library 2009, Issue 4): eight reports of which one (Takao 2004), subsequently excluded, focused on osteochondral defects of the talus.

• MEDLINE (1950 to November week 3 2009): 71 reports of which 21 focused on osteochondral defects of the talus. Only one was an account of a randomised trial, which is currently ongoing (van Bergen 2009).

• MEDLINE In‐Process (December 2009): one non eligible study.

• EMBASE (1988 to December 2009) search: 41 reports of which 11 focused on osteochondral defects of the talus but none of these was a comparative study.

Searching Current Controlled Trials and the WHO International Clinical Trials Registry Platform for ongoing and recently completed trials (28 December 2009) produced just one ongoing trial (van Bergen 2009).

Included studies

One trial (Bilge 2009) involving a total of 15 adult patients is included in this review. This trial compared the effect of intraarticular Hyaluronan injection after arthroscopic debridement and microfracture of osteochondral defect of the talus. Bilge 2009 was reported in a conference abstract only. Full details are given in the Characteristics of included studies.

We failed to locate any other completed randomised trials. Details of an ongoing trial (van Bergen 2009) evaluating pulsed electromagnetic fields after arthroscopic treatment are presented in the Characteristics of ongoing studies.

Excluded studies

Brief details of the three excluded trials including reasons for their exclusion are given in the Characteristics of excluded studies. It is noteworthy that two of these trials (Gobbi 2006; Takao 2004) claimed to be randomised.

Risk of bias in included studies

The lack of information in the abstract report of Bilge 2009 meant that the risk of bias was unclear for most items. In particular, the small number of participants involved, increasing the possibility of selection bias, and the lack of assessor blinding meant that Bilge 2009 was judged as being at risk of serious bias. A risk of bias table is in the Characteristics of included studies.

Allocation

Bilge 2009 reported the method of randomisation was by envelope, but gave no details of sequence generation or safeguards to ensure allocation concealment.

Blinding

There was no mention of assessor or patient blinding. Patient and care provider blinding were unlikely given the lack of a placebo control.

Incomplete outcome data

Bilge 2009 gave no report of loss of patients to follow‐up at six months. Personal communication by email with the lead trialist resulted in no data relating to the six‐month follow‐up.

Selective reporting

There was insufficient information, including no trial registration, to make judgement on this for Bilge 2009.

Other potential sources of bias

There was a lack of information to judge on three other potential sources of bias: bias resulting from major imbalances in key baseline characteristics, performance bias and sponsorship bias.

Effects of interventions

The only intervention evaluated by a randomised controlled trial was intraarticular hyaluronan injection, started three weeks after surgery (arthroscopic debridement and microfracture). Bilge 2009 provided no outcome data in their small trial of 15 patients at six‐month follow‐up.

Bilge 2009 reported there was no significant effect on the Freiburg pain index resulting from intraarticular hyaluronan (reported P > 0.05). Relative to pre‐operative "Foot and Ankle Index" function scores, Bilge 2009 reported a significant clinical improvement for all participants in two subcategories: walking four blocks and walking fast (reported P < 0.05). Bilge 2009 reported a significant improvement in the injection group for the subcategory of walking four blocks (reported P < 0.05). However, Bilge 2009 concluded the effect of intraarticular hyaluronan was insignificant compared with the non‐injection group.

Discussion

Summary of main results

The sole randomised controlled trial included in this review was reported only in a conference abstract and provided no quantitative results for an evaluation of intraarticular hyaluronan injection after arthroscopic debridement and microfracture of osteochondral defects of the talus in 15 adults. Bilge 2009 reported a lack of significant effect from hyaluronan injection. However, this trial was underpowered and at risk of serious bias.

An important finding of this review is that one allegedly randomised trial (Gobbi 2006), which compared three surgical interventions, was not randomised or quasi‐randomised. An erratum was published retracting the level 1 status of evidence and classifying as level 2 (Gobbi 2008). Upon further clarification from contacting the lead trial author, it became clear that this was a comparative study only (seeCharacteristics of excluded studies).

Overall completeness and applicability of evidence

While the intervention tested in Bilge 2009 is relevant to the treatment of osteochondral defects of the talus, the above‐mentioned limitations of this trial nullify any consideration of the applicability of its findings.

Quality of the evidence

Bilge 2009 had methodological and reporting weaknesses making it highly susceptible to bias. Among the concerns are the very small number of participants, the absence of blinding and short follow‐up.

Potential biases in the review process

The authors think it unlikely that the review process has introduced bias. However, while the search was comprehensive, it is possible that we have missed small trials that are either unreported or just reported in conference abstracts. One strength of the review is that we have contacted trial authors for further clarification on methods.

Agreements and disagreements with other studies or reviews

There are many, mostly narrative, reviews on the treatment of osteochondral defects in the literature: a rapid Pubmed search (((talus) OR talar) AND osteochondral) for relevant review articles produced 69 results. Two more recent reviews are described here. The most recent systematic review (Zengerink 2010) included randomised and non‐randomised studies. (Case reports and studies with less than 10 patients, under 18 year olds, follow‐up of less than 6 months or combination diagnose and treatment were excluded.) Zengerink 2010 included 52 studies with 1361 patients. While they identified one RCT (Gobbi 2006), they later questioned the methods of this study. Zengerink 2010 concluded that, given the variability in articles and treatment results, no definitive conclusions can be drawn from the available evidence.

A Cochrane review (Wasiak 2006) on treating osteochondral defects of the knee with different surgical interventions included four randomised trials. They concluded that there was no current evidence of a significant difference between autologous chondrocyte implantation and other chondral resurfacing interventions. However, caution is required when referring to evidence from trials on a different anatomical joint.

Authors' conclusions

Implications for practice.

Overall, there is currently no evidence from randomised controlled trials to determine which intervention is the most appropriate for the treatment of osteochondral defects of the talus in adults.

Implications for research.

Osteochondral defects of the talus, although relatively rare, can be seriously disabling. There remains a need to ascertain the best interventions to manage these defects. There has been considerable research in osteochondral defects over the past few decades but this has mainly concentrated on the treatment of osteochondral defects to the knee. The ankle joint is anatomically different to the knee, with different loading patterns, and this merits specific research on treatment interventions for osteochondral defects of the talus. The main limitation in comparison of the different surgical techniques is the associated comorbidity from harvesting cartilage cells and then implantation of these cells. Osteochondral autograft transfer grafts (OATS) and autologous chondrocyte implantation (ACI) both require two surgical procedures whereas arthroscopic debridement with microfracture is a single surgical procedure. OATS creates a defect in another joint surface unlike ACI. Interest has therefore been directed to developing arthroscopic techniques for ACI. With a prior minor procedure to harvest cartilage cells, a comparison of arthroscopic ACI and arthroscopic microfracture would be possible. Two comparable operations would enable a randomised controlled trial comparing the treatment of osteochondral defects with substitute fibrocartilage or hyaline‐like cartilage.

It is important that any future research meets international recognised standards of design, including randomisation of treatment allocation, and reporting to limit confounding factors and the risk of bias as much as possible.

Appendices

Appendix 1. Search strategies

MEDLINE (Ovid interface)

1. Talus/ or Ankle/ or Ankle Joint/ or Ankle Injuries/ 
 2. (talus or talar or ankle or talotibia$ or talo‐tibia$ or tibiotal$ or tibio‐tal$ or talocrural).tw. 
 3. or/1‐2 
 4. exp Cartilage/ or exp Osteochondritis/ or Osteochondrosis/ 
 5. (osteochond$ or cartilag$).tw. 
 6. or/4‐5 
 7. and/3,6 
 8. Randomized Controlled Trial.pt. 
 9. Controlled Clinical Trial.pt. 
 10. randomized.ab. 
 11. placebo.ab. 
 12. Drug Therapy.fs. 
 13. randomly.ab. 
 14. trial.ab. 
 15. groups.ab. 
 16. or/8‐15 
 17. exp Animals/ not Humans/ 
 18. 16 not 17 
 19. and/7,18  (87 records)

EMBASE (Ovid interface)

1. Talus/ or Talocrural, Joint/ or Talus Fracture/ or Ankle/ or Ankle Fracture/ or Ankle Injury/ 
 2. (talus or talar or ankle or talocrural or talotibia$ or talo‐tibia$ or tibiotal$ or tibio‐tal$).tw. 
 3. or/1‐2 
 4. Articular Cartilage/ or Cartilage/ or Osteochondritis Dissecans/ or Osteochondritis/ or Osteochondral Talar Defect/ or Osteochondrosis/ 
 5. (osteochond$ or cartilag$).tw. 
 6. or/4‐5 
 7. and/3,6 
 8. Clinical Trial/ 
 9. Randomized Controlled Trial/ 
 10. Randomization/ 
 11. Single Blind Procedure/ 
 12. Double Blind Procedure/ 
 13. Crossover Procedure/ 
 14. Placebo/ 
 15. randomi?ed controlled trial$.tw. 
 16. rct.tw. 
 17. random allocation.tw. 
 18. randomly allocated.tw. 
 19. allocated randomly.tw. 
 20. (allocated adj2 random).tw. 
 21. single blind$.tw. 
 22. double blind$.tw. 
 23. ((treble or triple) adj blind$).tw. 
 24. placebo$.tw. 
 25. Prospective Study/ 
 26. or/8‐25 
 27. Case Study/ 
 28. Case Report.tw. 
 29. Abstract Report/ or Letter/ 
 30. or/27‐29 
 31. 26 not 30 
 32. limit 31 to Human 
 33. and/7,32

The Cochrane Central Register of Controlled Trials (Wiley InterScience interface)

#1 MeSH descriptor Talus, this term only 
 #2 MeSH descriptor Ankle, this term only 
 #3 MeSH descriptor Ankle Joint, this term only 
 #4 MeSH descriptor Ankle Injuries, this term only 
 #5 (talus or talar or ankle or talotibia* or talo‐tibia* or tibiotal* or tibio‐tal* or talocrural):ti,ab 
 #6 (#1 OR #2 OR #3 OR #4 OR #5) 
 #7 MeSH descriptor Cartilage explode all trees 
 #8 MeSH descriptor Osteochondritis explode all trees 
 #9 MeSH descriptor Osteochondrosis, this term only 
 #10 (osteochond* or cartilag*):ti,ab 
 #11 (#7 OR #8 OR #9 OR #10) 
 #12 (#6 AND #11)

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Bilge 2009.

Methods	Randomisation: "by envelope" Clinician and patient blinding; not stated
Participants	Study conducted in Ankara, Turkey, between January 2003 and February 2006. 15 adults with chronic ankle pain who had MRI confirmation of osteochondral lesion of the talus Mean age: 39 ± 11 (SD) 8 men and 7 women
Interventions	All trial participants had arthroscopic debridement and microfracture to osteochondral defects. Patients were mobilised without weight‐bearing on the first post‐operative day and were fully weight‐bearing in the third week after their operation. 1. Intraarticular hyaluronan injection ("half dose"), started at 3 weeks post‐operatively and then weekly for 3 weeks. 2. Control: no injection. Allocation: 6 versus 9
Outcomes	Length of follow‐up: 6 months (Referral to surveys being filled by trial participants, pre‐operatively and ninth week post‐operatively) Functional assessment: "the foot and ankle function index" Pain analysis: "pain category of the Freiburg index"
Notes	Trial is only published in a conference abstract. Outcome scores not reported. Personal communication with Dr O Bilge by email revealed that follow‐up has been continued for two years and that data collection will be complete in the latter half of 2010. Full details of the results will then be made available.
Risk of bias
Bias	Authors' judgement	Support for judgement
Adequate sequence generation?	Unclear risk	No mention of how randomisation sequence was generated: "6 patients randomized by envelope"
Allocation concealment?	Unclear risk	No mention of safeguards: "6 patients randomized by envelope"
Blinding? Patient related outcomes	High risk	Not reported but this does not appear to be a placebo controlled trial and thus patients are aware of allocated intervention.
Blinding? Clinican related outcomes	High risk	Not reported but this does not appear to be a placebo controlled trial and thus clinicians are aware of allocated intervention.
Incomplete outcome data addressed? All outcomes	Unclear risk	Insufficient reporting to permit judgement
Free of selective reporting?	High risk	No indication of a protocol and incomplete reporting of results.
Balanced baseline characteristics?	Unclear risk	No information available. There is a high risk of imbalances in key baseline characteristics resulting from the small sample size.
Free from performance bias?	Unclear risk	No details given of the care provided to trial participants other than the trial interventions. Unknown but potential differences between the trial groups in the scheduling of follow‐up could also affect trial outcome.
Free from sponsorship bias?	Unclear risk	No details available.

Characteristics of excluded studies [ordered by study ID]

Study	Reason for exclusion
Gobbi 2006	A prospective comparative study, conducted the three hospitals, that involved 32 patients with symptomatic, recalcitrant Ferkel class 2b, 3, and 4 osteochondral lesions diagnosed by MRI and ankle arthroscopy. The study compared chondroplasty versus mosaicplasty versus osteochondral autograft transplantation and reported results at 24 months. Originally reported as a randomised study but an erratum was later published (Gobbi 2008). On personal communication, Mr Alberto Gobbi verified that treatment selection was determined by the patient's address. Each surgeon used a specific technique and patient intervention was selected according to the distance of their location from each surgeon. This method of treatment allocation was considered to overstretch the definition of a quasi‐RCT and put the trial at high risk of bias. No randomisation of treatment occurred and hence this study was excluded.
Koulalis 2009	A comparative study, only reported in a conference abstract, involving 20 patients with osteochondral defects of the ankle joint, 10 of whom were treated with autologous osteochondral transplantation and 10 with autologous chondrocyte transplantation. There was no indication that this was a randomised controlled trial and there were notable differences between the two groups in the average lesion sizes.
Takao 2004	Comparative study involving 69 patients who had arthroscopic drilling of osteochondral defects of the talus with or without removal of unstable cartilage. Though claimed to be randomised, the two intervention groups were not concurrent and thus this was not a randomised controlled trial.

Characteristics of ongoing studies [ordered by study ID]

van Bergen 2009.

Trial name or title	Pulsed electromagnetic fields after arthroscopic treatment for osteochondral defects of the talus
Methods	Double‐blind randomised controlled multi‐centre trial
Participants	68 participants intended Inclusion criteria: 1. Patients with a symptomatic OD of the talus who are scheduled for arthroscopic debridement and microfracture; 2. OD diameter < 15 mm on computed tomography; 3. Ankle Activity Score (AAS) ≥ 4 before symptoms; 4. Age 18 years or older. Exclusion criteria: 1. Concomitant OD of the tibia; 2. Ankle osteoarthritis grade 2 or 3; 3. Ankle fracture < 6 months before scheduled arthroscopy; 4. Surgical treatment of the index ankle performed < 1 year before scheduled arthroscopy; 5. Concomitant painful or disabling disease of the lower limb; 6. Rheumatoid arthritis; 7. Pregnancy; 8. Implanted pacemaker; 9. Participation in concurrent trials; 10. Participation in previous trials < 1 year, in which the subject has been exposed to radiation (radiographs or CT); 11. Patients who are unable to fill out questionnaires and cannot have them filled out; 12. No informed consent.
Interventions	In both groups the investigational treatment (active PEMF‐treatment or sham device treatment) will start three days after surgery. It will be applied four hours daily (in one or two sessions) for a period of 60 days .
Outcomes	Primary outcome: 1. The number of patients that resume and maintain sports during 12 months follow‐up; 2. The time to resumption of sports, defined by the AAS (Ankle Activity Score). Secondary outcome: 1. Time to resumption of work; 2. American Orthopaedic Foot and Ankle Society ‐ Ankle and Hindfoot clinical rating System (AOFAS‐AHS); 3. Foot and Ankle Outcome Score (FAOS); 4. Quality of life (EuroQol); 5. Pain; 6. Satisfaction; 7. Computed tomography evaluation; 8. Adverse events.
Starting date	17 Feb 2009
Contact information	Dr CJA van Bergen Academisch Medisch Centrum Meibergdreef 9, Amsterdam, 1105 AZ, The Netherlands c.j.vanbergen@amc.nl
Notes	This is an ongoing trial, the protocol of which is published in BMC Musculoskeletal Disorders

Differences between protocol and review

We modified search strategies to increase sensitivity. CINAHL was not searched nor did we search conference proceedings.

Contributions of authors

The protocol was conceived and designed by DL and AR. The search strategies (in association with Dr Joanne Elliott at the Cochrane Bone, Joint and Muscle Trauma Group) and methods were developed by DL and RC. Trial quality assessment and data extraction were by DL and RC. DL wrote the review with critical appraisal from RC and AR. DL is the guarantor for the protocol.

Sources of support

Internal sources

• Addenbrooke's Hospital, Cambridge, UK.

  Library services

External sources

• No sources of support supplied

Declarations of interest

None known.

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