TITLE: The Use of Osteochondral Allograft for the Ankle, … · Seven systematic reviews (SRs) were found on clinical benefits and harms of osteochondral allograft transplantation

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TITLE: The Use of Osteochondral Allograft for the Ankle, Knee, and Shoulder: Clinical Effectiveness and Cost-Effectiveness

DATE: 09 February 2017

CONTEXT AND POLICY ISSUES

Articular cartilage is the smooth, white tissue that covers the ends of bones in joints.1 Healthy articular cartilage makes it easy for joints to move.1 However, this tissue can be damaged through injury or normal wear-and-tear.1 Because damaged articular cartilage does not heal by itself, if it is left untreated, significant destruction of the joint, or osteoarthritis, may ensue.2 A number of treatment options are available for damaged articular cartilage but are often aimed at treating symptoms rather than providing a cure.2 For example, non-surgical methods, such as physiotherapy, may relieve pain but cannot heal cartilage.2 Surgical treatments aimed at preserving the joint are increasingly available.2 Microfracture and drilling are minimally-invasive procedures that promote bleeding from the bone2 to stimulate the growth of cartilage by creating a new blood supply.1 Mosaicplasty is an autograft transplantation procedure, in which a block of osteochondral (i.e., bone and cartilage) tissues is harvested from a less-demanding (e.g., non-weight-bearing) area of a joint to cover a cartilage defect in a more important (e.g., weight-bearing) area within a single patient.2 If a cartilage defect is too large for an autograft1,2 or in patients who failed other cartilage repair techniques,3 an allograft transplantation treatment, in which osteochondral tissues are harvested from cadavers, may be used to cover the injured area.1-3 Historically, allografts have been implanted fresh within 24 hours of procurement. However, concerns about disease transmission have led to required bacterial and viral testing before tissue release, which takes a minimum of 14 days.3 Today, harvested tissues may be aseptically-processed and maintained at four degrees Celsius as prolonged fresh allografts, which are most common, or cryopreserved into frozen allografts until use.3 To inform clinical practice on the treatment of patients who failed non-surgical or other surgical therapies for damaged articular cartilage, this report aimed to provide evidence on the clinical benefits and harms and cost-effectiveness of the use of fresh, prolonged fresh, or frozen osteochondral allografts for the lesions of the ankle, knee, and shoulder.

The Use of Osteochondral Allograft for the Talus, Knee, and Shoulder 2

RESEARCH QUESTIONS

1. What is the clinical effectiveness regarding the use of osteochondral allograft for the

ankle? 2. What is the cost-effectiveness regarding the use of osteochondral allograft for the ankle? 3. What is the clinical effectiveness regarding the use of osteochondral allograft for the knee? 4. What is the cost-effectiveness regarding the use of osteochondral allograft for the knee? 5. What is the clinical effectiveness regarding the use of osteochondral allograft for the

shoulder? 6. What is the cost-effectiveness regarding the use of osteochondral allograft for the

shoulder? KEY FINDINGS

Seven systematic reviews (SRs) were found on clinical benefits and harms of osteochondral allograft transplantation for the ankle, knee, and shoulder. For all three joints, while the operation can improve pain and functional outcomes, with a high level of patient satisfaction, high rates of complications, reoperations, and clinical failures were reported. The quality of the SRs was mixed, and the quality of the primary studies included in those SRs was generally poor, warranting caution in the interpretation of the findings. No economic evaluations fulfilling the selection criteria were found. METHODS

Literature Search Methods

A limited literature search was conducted on key resources, including PubMed, The Cochrane Library, University of York Centre for Reviews and Dissemination (CRD) databases, and Canadian and major international health technology agencies. A focused Internet search was also conducted. Methodological filters were applied to limit retrieval to health technology assessments (HTAs), SRs, meta-analyses (MAs), and economic studies. Where possible, retrieval was limited to the human population. The search was also limited to English language documents, published between January 1, 2012 and January 10, 2017. Selection Criteria and Methods

One reviewer screened citations and selected studies. In the first level of screening, titles and abstracts were reviewed, and potentially-relevant articles were retrieved and assessed for inclusion. The final selection of full-text articles was based on the inclusion criteria presented in Table 1.


Table 1: Selection Criteria

Population Healthy, active patients between the ages of 18-55 years, with a documented, painful lesion of the ankle, knee, or shoulder that involves cartilage or cartilage with bone and has failed non-operative and primary operative treatment

Intervention Q1, Q2: Osteochondral allograft for the ankle Q3, Q4: Osteochondral allograft for the knee Q5, Q6: Osteochondral allograft for the shoulder

Comparator Any comparator, including before-and-after Outcomes Q1, Q3, Q5: Clinical effectiveness and functional outcomes

Q2, Q4, Q6: Cost-effectiveness Study Designs

HTAs, SRs, MAs, and economic evaluations

HTA = health technology assessment; MA = meta-analysis; SR = systematic review

Exclusion Criteria

Articles were excluded if they did not meet the selection criteria for the intervention, comparator, outcomes, and study designs that are outlined in Table 1, if they were duplicate publications or SRs superseded by more comprehensive SRs, or if they were published prior to 2012. For the selection criteria for the population outlined in Table 1, because selecting the literature based on the terms healthy, active, and ages of 18-55 years was found to be too restrictive, only articles focusing on specific diseases, children, or seniors were excluded. For articles missing information on prior interventions, it was assumed that the patients had failed non-surgical or other surgical therapies for damaged articular cartilage.3 Critical Appraisal of Individual Studies

The included SRs were critically appraised, using the Assessment of Multiple Systematic Reviews (AMSTAR) tool.4 Summary scores were not calculated for the included studies; rather, the strengths and limitations of each included study were narratively described. SUMMARY OF EVIDENCE

Quantity of Research Available

A total of 150 citations were identified in the literature search. Following screening of titles and abstracts, 126 citations were excluded, and 24 potentially-relevant reports from the electronic search were retrieved for full-text review. No potentially-relevant publications were retrieved from the grey literature search. Of the 24 potentially-relevant articles, 17 publications were excluded for various reasons, while seven publications met the inclusion criteria and were included in this report. One SR

5 was identified that examined osteochondral allograft

transplantation for the knee, but it focused on randomized controlled trials and did not identify any relevant studies, and therefore was not included in this report. Appendix 1 describes the PRISMA flowchart of the study selection. Additional references of potential interest that did not meet the selection criteria are provided in Appendix 5.


Summary of Study Characteristics

A summary of the characteristics of the included literature is presented in Appendix 2. Clinical Benefits and Harms of Osteochondral Allograft for the Ankle A total of two SRs6,7 provided information on the clinical effectiveness and safety of osteochondral allograft transplantation for the ankle. Study Design The SRs6,7 included five case-series studies6 or 13 studies, most of which were also case-series.7 Although all five case-series studies included in one SR6 were also included in the other SR,7 to present all outcomes described, both SRs6,7 were included in this report. Neither of the SRs6,7 included control groups. One SR6 conducted searches up to 2016 and was published in 2017, and the other SR7 did not provide search dates and was published in 2016. Country of Origin The SRs

6,7 were conducted in the United States (US).

Patient Population The SRs6,7 included patients with osteochondral lesions of the ankle. One SR6 included adults aged 17 to 74 years, most of who had undergone one or more prior interventions on the ankle, whereas the other SR7 included patients with unknown age and did not report on prior interventions on the ankle. Interventions and Comparators The SRs6,7 included osteochondral allograft transplantation as the intervention and compared it to before the operation. One SR6 included fresh allografts only, whereas the other SR7 did not specify such restriction. Outcomes The SRs

6,7 included various measures of foot and ankle pain and function, including the

American Orthopedic Foot and Ankle Society score (AOFAS),6,7 foot function index (FFI) score,6 and visual analog scale (VAS) pain score.6 One SR6 included patient satisfaction, reoperation, and failure rates. One SR6 reported a mean follow-up of 45 months, whereas the other SR7 did not report on follow-up durations. One SR6 conducted quality assessment of the included studies, using the Coleman Methodology Score, which was based on the following 10 items: study size, follow-up duration, number of surgical procedures, study design, diagnostic certainty, description of surgical procedures, description of postoperative rehabilitation, outcome measures, outcome assessment, and selection process.


Cost-Effectiveness of Osteochondral Allograft for the Ankle No economic evaluations fulfilling the selection criteria were found. Clinical Benefits and Harms of Osteochondral Allograft for the Knee A total of four SRs3,8-10 provided information on the clinical effectiveness and safety of osteochondral allograft transplantation for the knee. Study Design The SRs3,8-10 included five cohort or case-series studies8 or one,9 three,10 or 193 case-series studies. Although there was partial3,8,10 or complete9,10 overlap in the included studies across the SRs, to present all outcomes described, all four SRs3,8-10 were included in this report. None of the SRs3,8-10 included control groups. Three SRs8-10 conducted searches up to 2014,9 2015,8 or 201610 and were published in 2016, and the other SR3 conducted searches up to 2012 and was published in 2013. Country of Origin Three SRs8-10 were conducted in the US, and the other SR3 was conducted in Canada. Patient Population The SRs3,8-10 included patients with chondral3,8-10 or osteochondral8,9 lesions of the knee. One SR8 included adults aged 15 to 69 years, most of who had undergone one or more prior interventions on the knee. Two SRs,9,10 with overlapping patient populations, included athletic adults, with a mean age of 33 years and 1.33 previous knee surgeries on average. One SR3 included adults aged 20 to 62 years, with 1.7 previous knee surgeries on average. Interventions and Comparators The SRs3,8-10 included osteochondral allograft transplantation as the intervention and compared it to before the operation. One SR8 included fresh allografts only, another SR3 included fresh, prolonged-fresh, and fresh-frozen allografts, and the other SRs9,10 did not specify any restriction on the type of allograft. Three SRs3,8,10 reported that some patients were treated with concomitant procedures, including tibial tubercle transfer and extensor mechanism realignment,8 osteotomy,3,8 meniscal transplantation,3,8 ligamentous reconstruction,10 and retinacular release.3 Outcomes The SRs3,8-10 included various measures of knee pain and function, including the hospital special surgery (HSS) score,8 Knee Society score (KSS),8 Lysholm score,3,8 knee injury and osteoarthritis outcome score (KOOS),9,10 International Knee Documentation Committee (IKDC) score,3,9 Marx score,9 and Tegner scale score.3,10 Three SRs8-10 included return-to-activities8 or return-to-sports9,10 rates. Three SRs3,8,9 included complication,3,8,9 reoperation,8,9 and failure3,8 rates. Two SRs3,8 included survival rates. One SR3 included patient satisfaction rates.


One SR8 included long-term follow-up only and reported a mean follow-up of 12.3 years, whereas the other SRs3,9,10 reported a mean follow-up of 32 months to 58 months. The SRs3,8-10 conducted quality assessment of the included studies, using the Coleman Methodology Score.

Cost-Effectiveness of Osteochondral Allograft for the Knee No economic evaluations fulfilling the selection criteria were found. Clinical Benefits and Harms of Osteochondral Allograft for the Shoulder One SR11 provided information on the clinical effectiveness and safety of osteochondral allograft transplantation for the shoulder. Study Design The SR

11 included three case-series studies, with no control groups. The SR

11 conducted

searches up to 2014 and was published in 2014. Country of Origin The SR11 was conducted in Italy. Patient Population The SR11 included adult patients, aged 32 to 56 years, with shoulder instability. The SR11 did not report on prior interventions on the shoulder. Interventions and Comparators The SR11 included osteochondral allograft transplantation as the intervention and compared it to before the operation. The SR11 did not specify any restriction on fresh or frozen allografts. Outcomes The SR

11 included various measures of shoulder pain and function, including the Constant

score, recurrence rate of shoulder instability, and range of shoulder motion. The SR11 also included complication rates. The SR11 reported a mean follow-up of 54 months to 68 months across the included studies and conducted quality assessment of the included studies, using the Coleman Methodology Score.

Cost-Effectiveness of Osteochondral Allograft for the Shoulder No economic evaluations fulfilling the selection criteria were found. Summary of Critical Appraisal

A summary of the critical appraisal of the included literature is presented in Appendix 3.


Clinical Benefits and Harms of Osteochondral Allograft for the Ankle The two SRs6,7 on osteochondral allograft transplantation for the ankle were of mixed quality, based on the assessment conducted with the AMSTAR tool.4 One SR6 conducted triplicate study selection, provided a list of the included studies and their characteristics, and used appropriate methods to combine data but did not describe data extraction, provide a search strategy or a flow diagram for the search results, or assess the scientific quality of the included studies. The other SR7 conducted duplicate data extraction, provided a detailed search strategy and a flow diagram for the search results, and assessed the scientific quality of the included studies but did not conduct duplicate study selection, provide a list of the included studies or their characteristics, or describe the methods used to combine data. Neither of the SRs6,7 provided an a priori design, conducted a comprehensive literature search, listed the excluded studies, or addressed publication bias. Both SRs6,7 disclosed potential conflicts of interest. Clinical Benefits and Harms of Osteochondral Allograft for the Knee The four SRs3,8-10 on osteochondral allograft transplantation for the knee were of mixed quality, based on the assessment conducted with the AMSTAR tool.

4 Most or all of the SRs provided a

detailed search strategy,3,8,10 a flow diagram for the search results,3,8,10 or a list of the included studies and their characteristics;

3,8-10 used appropriate methods to combine data;

3,8-10 or

assessed the scientific quality of the included studies.3,8-10 However, none of the SRs3,8-10 provided an a priori design, conducted a comprehensive literature search or fully duplicate study selection and data extraction, listed the excluded studies, or addressed publication bias. Three SRs8,9,11 disclosed potential conflicts of interest. Clinical Benefits and Harms of Osteochondral Allograft for the Shoulder The one SR3 on osteochondral allograft transplantation for the shoulder was of mixed quality, based on the assessment conducted with the AMSTAR tool.4 The SR3 conducted triplicate study selection and data extraction and a comprehensive literature search; provided a flow diagram for the search results and a list of the included studies and their characteristics; used appropriate methods to combine data; assessed the scientific quality of the included studies; and declared no conflict of interest. However, the SR3 did not provide an a priori design, a detailed search strategy, or a list of the excluded studies and did not address publication bias. Summary of Findings A summary of the findings of the included literature is presented in Appendix 4. What is the clinical effectiveness regarding the use of osteochondral allograft for the ankle? Pain and Functional Outcomes One SR6 reported that patients with osteochondral lesions of the ankle experienced improved pain and functional outcomes after osteochondral allograft transplantation, compared to before, assessed by the mean AOFAS, FFI, and VAS pain scores. Another SR7 reported that the postoperative median AOFAS score indicated good to excellent results from the operation but did not provide the preoperative score.


Patient Satisfaction Rates One SR6 reported that 70.5% of patients with osteochondral lesions of the ankle reported good to excellent satisfaction with the operation. Reoperation and Failure Rates One SR6 reported that 25.3% of patients with osteochondral lesions of the ankle required at least one reoperation of any kind, with 8.8% of ankles requiring arthrodesis (i.e., ankle fusion) and arthroplasty (i.e., ankle replacement). The SR6 reported that 13.2% of all operations were considered failures, defined as postoperative graft nonunion or resorption or persistence of symptoms leading to subsequent arthrodesis or arthroplasty. What is the clinical effectiveness regarding the use of osteochondral allograft for the knee? Pain and Functional Outcomes Four SRs

3,8-10 reported that patients with chondral

3,8-10 or osteochondral

8,9 lesions of the knee

experienced improved pain and functional outcomes after osteochondral allograft transplantation, compared to before, assessed by the mean KSS,

8 Lysholm,

3,8 KOOS,

10 IKDC,

3,9

Marx,9 and Tegner scale3 scores. One SR8 reported that the postoperative HSS8 score indicated good results from the operation but did not provide the preoperative score. Survival Rates Two SRs3,8 reported that patients with chondral3,8 or osteochondral8 lesions of the knee had 91-95%, 76-85%, and 71-76% survival rates at five, 10, and 15 years after the operation. One SR8 reported that the largest decrease in estimated survival occurred between the 15- and 20-year time-points from 71% to 45%, respectively. No information on the relationship between the intervention and survival were provided, and no control group was used to determine how these rates might differ from the general population. Return-to-Activities and Return-to-Sports Rates One SR8 reported that patients with chondral or osteochondral lesions of the knee returned to non-weight-bearing activities after 8.4 weeks on average and full activities after 5.9 months on average following the operation. It was unclear whether any patients were unable to return to full activities. Another SR9 reported that the majority of the patients had returned to sports and to preinjury-level performance by 30 months and 9.6 months following the operation, respectively. Patient Satisfaction Rates One SR3 reported that 86% of patients with chondral lesions of the knee reported being extremely or mostly satisfied with the operation. Complication, Reoperation, and Failure Rates Two SRs3,8 reported complications after the operation, with two cases of infection8 and 2.4% of knees having infections, deep vein thrombosis, hyperemic reaction, or early loosening of the graft.3 One SR9 reported that no complications were identified.


One SR8 reported that 36% of patients had reoperations, including knee arthroplasty, meniscus surgery, and ligament reconstruction. One SR9 reported that no reoperations were identified. Two SRs3,8 reported that 25% of all operations8 or 18% of knees that had operations3 were considered failures that required conversion to knee arthroplasty or graft revision or removal. What is the clinical effectiveness regarding the use of osteochondral allograft for the shoulder? Pain and Functional Outcomes One SR11 reported that patients with shoulder instability scored high on the Constant score after osteochondral allograft transplantation but did not provide the preoperative score. The SR11 reported that no patient experienced recurrence of shoulder instability after the operation and that the range of motion of the arm was restored or increased after the operation, compared to before the operation. Complication Rates One SR11 reported that 74% of patients with shoulder instability had complications after the operation. Complications included spontaneous avascular necrosis and collapse, persistent pain, clicking, catching, stiffness, and flattening. Limitations

There was partial or full overlap in the included studies across six SRs3,6-10. To present all outcomes included, all six SRs3,6-10 were included in this report, and care was taken to avoid presenting redundant findings, where possible. Nevertheless, there may be redundancy in the study findings presented in this report. Most, if not all, of the studies included in the SRs were of the retrospective, case-series type, with no control groups. Therefore, the data reported by the SRs were generally preoperative and postoperative values, or differences between, before and after the operation. Two SRs7,8 only reported postoperative values for pain and functional outcomes, probably because their included studies did not report preoperative values.3,6 Further, two SRs3,8 reported survival rates of patients following the operation, with no comparison to the baseline survival rates of individuals matched on age and other demographic factors. Therefore, the improvements observed following the operation may not be fully attributable to the intervention itself, and the impact of the intervention on survival rates is unclear. The patient populations included in the SRs were not always in full agreement with the selection criteria of this report. For example, the age ranges were either not within 18 to 55 years or not reported, and whether patients were healthy and active and prior interventions were not always reported.7,11 Because selecting the literature based on the terms healthy, active, and ages of 18-55 years outlined in Table 1 was found to be too restrictive, only articles focusing on specific diseases, children, or seniors were excluded. For articles missing information on prior interventions, it was assumed that the patients had failed non-surgical or other surgical therapies for damaged articular cartilage.3 Therefore, the findings presented in this report may not be entirely applicable to the specific population of interest described in Table 1.


The term osteochondral appears to be used in the literature to indicate osteochondral (i.e., bone and cartilage), osseous (i.e., bone only), and chondral (i.e., cartilage only) surgery. The SRs included in this report listed osteochondral surgery as their intervention of interest but did not always fully describe what types of allografts were transplanted. Further, three SRs3,8,10 reported that the operation had concomitant procedures. It is unclear whether the other SRs6,7,9,11 failed to report concomitant procedures or if their included studies did not have any. Therefore, the findings presented in this report may not be solely attributable to osteochondral allograft transplantation. All seven SRs3,6-11 identified heterogeneity in the patients populations (e.g., age,11 functional abilities,11 and lesion types10) and outcome measures (i.e., different scales for pain and function or different definitions for failures3) across the included studies as a concern that precluded a meta-analysis.8 One SR7 noted that a total of 38 different scoring systems were used to assess pain and functions outcomes in its included studies. Although four SRs8-11 reported that their included studies were assessed to be of fair8-10 or good11 quality, based on the Coleman Methodology Score, several SRs3,7,9,11 indicated that the current literature is of poor quality and with small samples. CONCLUSIONS AND IMPLICATIONS FOR DECISION OR POLICY MAKING

Two, four, and one SRs were found on clinical benefits and harms of osteochondral allograft transplantation for the ankle, knee, and shoulder, respectively. For all three joints, while the operation can improve pain and functional outcomes, with a high level of patient satisfaction, high rates of complications, reoperations, and clinical failures were reported. For the knee, decreasing survival rates over time were reported, with the largest drop estimated to occur between 15 and 20 years after the operation, though rates for a population not receiving osteochondral allografts were not reported, and a wide range of six to 30 months was reported as the time it took to return to activities or sports. The quality of the SRs was mixed, and the quality of the primary studies included in those SRs was generally poor, warranting caution in the interpretation of the findings. Prospective comparative studies with large samples, longer follow-up, and high quality are needed to confirm and clarify the findings presented in this report. No economic evaluations fulfilling the selection criteria were found. PREPARED BY:

Canadian Agency for Drugs and Technologies in Health Tel: 1-866-898-8439 www.cadth.ca

http://www.cadth.ca/


REFERENCES

1. Articular cartilage restoration. In: OrthoInfo [Internet]. Rosemont (IL): American Academy of Orthopaedic Surgeons; 2009 [cited 2017 Feb 9]. Available from: http://orthoinfo.aaos.org/topic.cfm?topic=a00422

2. Surgical treatment options (microfracture, drilling, mosaicplasty, and allograft

transplantation) for cartilage injuries of the knee in adults. In: Our evidence [Internet]. London: The Cochrane Collaboration; 2016 Sep 3 [cited 2017 Jan 18]. Available from: http://www.cochrane.org/CD010675/MUSKINJ_surgical-treatment-options-microfracture-drilling-mosaicplasty-and-allograft-transplantation

3. Chahal J, Gross AE, Gross C, Mall N, Dwyer T, Chahal A, et al. Outcomes of osteochondral allograft transplantation in the knee. Arthroscopy. 2013 Mar;29(3):575-88.

4. Shea BJ, Grimshaw JM, Wells GA, Boers M, Andersson N, Hamel C, et al. Development of AMSTAR: a measurement tool to assess the methodological quality of systematic reviews. BMC Med Res Methodol [Internet]. 2007;7:10. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1810543/pdf/1471-2288-7-10.pdf

5. Gracitelli GC, Moraes VY, Franciozi CE, Luzo MV, Belloti JC. Surgical interventions (microfracture, drilling, mosaicplasty, and allograft transplantation) for treating isolated cartilage defects of the knee in adults. Cochrane Database Syst Rev. 2016 Sep 3;9:CD010675.

6. VanTienderen RJ, Dunn JC, Kusnezov N, Orr JD. Osteochondral allograft transfer for treatment of osteochondral lesions of the talus: a systematic review. Arthroscopy. 2017 Jan;33(1):217-22.

7. Pinski JM, Boakye LA, Murawski CD, Hannon CP, Ross KA, Kennedy JG. Low level of evidence and methodologic quality of clinical outcome studies on cartilage repair of the ankle. Arthroscopy. 2016 Jan;32(1):214-22.

8. Assenmacher AT, Pareek A, Reardon PJ, Macalena JA, Stuart MJ, Krych AJ. Long-term outcomes after osteochondral allograft: a systematic review at long-term follow-up of 12.3 years. Arthroscopy. 2016 Oct;32(10):2160-8.

9. Campbell AB, Pineda M, Harris JD, Flanigan DC. Return to sport after articular cartilage repair in athletes' knees: a systematic review. Arthroscopy. 2016 Apr;32(4):651-68.

10. Krych AJ, Pareek A, King AH, Johnson NR, Stuart MJ, Williams RJ, III. Return to sport after the surgical management of articular cartilage lesions in the knee: a meta-analysis. Knee Surg Sports Traumatol Arthrosc. 2016 Aug 18.

11. Longo UG, Loppini M, Rizzello G, Ciuffreda M, Berton A, Maffulli N, et al. Remplissage, humeral osteochondral grafts, weber osteotomy, and shoulder arthroplasty for the management of humeral bone defects in shoulder instability: systematic review and quantitative synthesis of the literature. Arthroscopy. 2014 Dec;30(12):1650-66.

http://orthoinfo.aaos.org/topic.cfm?topic=a00422http://www.cochrane.org/CD010675/MUSKINJ_surgical-treatment-options-microfracture-drilling-mosaicplasty-and-allograft-transplantationhttp://www.cochrane.org/CD010675/MUSKINJ_surgical-treatment-options-microfracture-drilling-mosaicplasty-and-allograft-transplantationhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC1810543/pdf/1471-2288-7-10.pdf


APPENDIX 1: Selection of Included Studies

126 citations excluded

24 potentially-relevant articles retrieved for scrutiny (full text, if available)

0 potentially-relevant reports retrieved from

other sources (i.e., grey literature or

hand search)

24 potentially-relevant reports

17 reports excluded due to:

irrelevant population (1)

irrelevant intervention (5)

irrelevant study design (i.e., non-systematic reviews) (10)

already included in at least one of

the selected reports (1)

7 reports included in review

150 citations identified from electronic literature search

and screened


APPENDIX 2: Characteristics of Included Publications

Table A1: Characteristics of Included Systematic Reviews

First Author, Publication

Year, Country

Types and Numbers of

Primary Studies Included

Population Characteristics

Intervention Comparator(s) Clinical Outcomes, Length of Follow-Up

Ankle VanTienderen

6

2017

US

SR of 5 case-series studies, published

between 2009 and 2012

No quality assessment

90 adult* patients, 74 of who had undergone one or

more prior interventions**, with large osteochondral lesions of 91 ankles in total

*Aged 17 to 74 years

**Including arthroscopic microfractures, osteochondral autograft

procedures, bone grafting procedures, ankle fracture fixations, and talar fracture

fixations

Osteochondral allograft* transplantation

*Fresh only

Before operation AOFAS score, FFI score, VAS pain score, patient

satisfaction rate, reoperation rate, and failure rate

Mean follow-up of 453.3 months (range: 6-91

months)

Pinski7

2016 US

SR of 13 studies* Quality assessment

using modified Coleman Methodology Score

*While this SR included 83 studies

in total, 70 of them were on irrelevant interventions. Most

of 83 the included studies were case-

267 patients* with osteochondral lesions of the ankle, with no information

on prior interventions *Age: NR

Osteochondral allograft transplantation

Before operation AOFAS score Follow-up duration: NR




Year, Country





series, published between 1980 and 2013.

Knee

Assenmacher8

2016

US

SR of 1 cohort and 4 case-series

studies, published between 1997 and 2015

Quality assessment using modified

Coleman Methodology Score

291 adult* patients, the majority of who had

undergone one or more prior interventions**, with chondral or osteochondral

defects of 301 knees in total *Aged 15 to 69 years

**Including open reduction and internal fixations,

meniscectomy, arthrotomy, arthroscopy, osteotomy, debridement,

microfractures, ACI, loose body removal, meniscal surgery, extensor

alignment, chondroplasty, lateral release, tibial tubercle transfer, and

ligament reconstruction

Osteochondral allograft* transplantation**

*Fresh only

**Concomitant procedures were reported in 39% (tibial

tubercle transfer and extensor mechanism realignment), 25% (distal

femoral osteotomy), 15% (proximal tibial osteotomy), or 18%

(meniscal allograft transplantation) of the patients.

Before operation HSS score, KSS-F score, KSS-K score, Lysholm

score, survival rate, return-to-activities rate, complication rate,

reoperation* rate, and failure** rate

Mean follow-up of 12.3 years (range: 10-17.1 years)***

*Defined as any surgery on the same knee, whether it

was related or unrelated to the intervention

**Defined as conversion to unicompartmental or total knee arthroplasty, repeat

cartilage restoration, imaging evidence of osteochondral allograft

reabsorption or collapse revision graft fixation, graft removal, HSS scores >70,

or both KSS and Lysholm scores >70




Year, Country





***Studies with a minimum mean follow-up of 9 years

were included.

Campbell9

2016 US

SR of 1 case-series study*, published in 2012

Quality assessment using Coleman

Methodology Score *While this SR

included 20 studies in total, 19 of them were on irrelevant

interventions.

43 athletic* adult** patients, who had 1.1 previous surgeries*** on average,

with chondral defects or osteochondritis dissecans of the knee

*Playing professional, collegiate, or recreational

sports **Aged 18 to 49 years

***Not defined


Before operation KOOS ADL score, IKDC-S score, Marx score, return-to-sports rate and

performance, complication rate, and reoperation rate

Mean follow-up of 2.5 years

Krych10

2016

US

SR of 3 case-series studies*, published


Quality assessment using modified Coleman

Methodology Score *While this SR

included 44 studies in total, 41 of them were on irrelevant

96 athletic* adult** patients, who had 1.33 previous

surgeries*** on average, with chondral defects of the knee

*Playing mostly recreational sports

**Mean age of 331 years

***Not defined

Osteochondral allograft*

*60% of the patients had concomitant procedures, with ligamentous

reconstruction being the most common.

Before operation KOOS score, Tegner activity scale score, and

return-to-sports rate Mean follow-up of 324

months (range: 24-35 months)*

*Studies with a minimum mean follow-up of 2 years were included.




Year, Country





interventions.

Chahal3

2013 Canada

SR of 19 case-series studies, published between

1985 and 2012 Quality assessment


Unknown number of adult* patients, who had 1.7 previous surgeries** on

average, with chondral defects*** of 595 knees in total

*Aged 20 to 62 years

**Including debridement, loose body removal, microfractures, and lesion

fixations ***Indications including

post-traumatic defects, osteochondritis dissecans, osteonecrosis from all

causes, idiopathic causes, osteoarthritis, and chondromalacia patella

Osteochondral allograft* transplantation**

*Including fresh, prolonged fresh, and fresh frozen

**46% of the patients had concomitant

procedures, including osteotomy, meniscal transplantation, and

retinacular release.

Before operation IKDC score, Lysholm score, Tegner scale score, survival rate, patient

satisfaction rate, complication rate, and failure rate

Mean follow-up of 58 months (range: 19-120

months)* *Studies with a minimum

mean follow-up of 12 months were included.

Shoulder

Longo11

2014

Italy

SR of 3 case series studies*, published


Quality assessment

23 adult* patients with posterior shoulder

instability**, with no information on prior interventions


Before operation Constant score, recurrence rate of shoulder instability,

range of motion, and complication rate

Mean follow-up of 54-68




Year, Country






*While this SR included 26 studies

in total, 23 of them were on irrelevant interventions.

*Mean age of 32-56 years (range: 28-76 years)

**Associated with Hill-Sachs or other types of fracture

months (range: 41-76 months)

ACI = autologous chondrocyte implantation; ADL = activity of daily living; AOFAS = American Orthopaedic Foot and Ankle Society; FFI = foot functional index; HSS = hospital for

special surgery; IKDC = International Knee Documentation Committee; IKDC-S = International Knee Documentation Committee-subjective; KOOS = knee injury and osteoarthritis outcome scale; KSS-F = Knee Society function score; KSS-K = Knee Society knee score; NR = not reported; SR = systematic review; US = United States; VAS = visual analog scale


APPENDIX 3: Critical Appraisal of Included Publications

Table A2: Strengths and Limitations of Included Systematic Reviews Using AMSTAR4

Strengths Limitations Ankle

VanTienderen 20176

There was triplicate study selection.

A list of the included studies and their characteristics were provided.

The methods used to combine the study findings were appropriate.

An a priori design was not provided.

It is unclear whether data extraction was performed by more than one reviewer.

Although several literature databases were searched, grey literature was not included. Neither a search strategy nor a flow diagram for the search results was provided.

A list of the excluded studies was not provided.

The scientific quality of the included studies was not assessed.

The scientific quality of the included studies was not used in formulating conclusions.

The likelihood of publication bias was not assessed.

One of the authors disclosed a potential conflict of interest, receiving support from a medical device company.

Pinski 20167

There was duplicate data extraction.

A detailed search strategy and a flow diagram for the search results were provided.

The scientific quality of the included studies was assessed and documented.

The scientific quality of the included studies was used appropriately in formulating conclusions.


There was no duplicate study selection.

Although several literature databases were searched, grey literature was not included.

A list of the included studies and their characteristics were not provided.


The methods used to combine the study findings were not described.


One of the authors disclosed potential conflicts of interest, receiving support from a medical device company and private donors.

Knee

Assenmacher 20168




The scientific quality of the


There was no duplicate study selection or data extraction.


A list of the excluded studies was not provided. The likelihood of publication bias was not assessed.

Three of the authors disclosed potential conflicts of interest, receiving support from medical device companies.


Table A2: Strengths and Limitations of Included Systematic Reviews Using AMSTAR4 Strengths Limitations

included studies was used appropriately in formulating conclusions.


Campbell 20169

There was duplicate data extraction.





Although study selection was performed by multiple authors, in the event of disagreement, decisions were made by the corresponding author, instead of through discussion and consensus.

Although several literature databases were searched, grey literature was not included. Neither a search strategy nor a flow diagram for the search results was provided.


The scientific quality of the included studies was not used in formulating conclusions.


Two of the authors disclosed potential conflicts of interest, receiving support from medical device and publishing companies.

Krych 201610







There was no duplicate study selection and no duplicate data extraction.




Four of the authors disclosed potential conflicts of interest, receiving support from medical device companies and serving on various government, interest group, or journal boards.

Chahal 20133

Data were extracted by one reviewer and verified by another.

A detailed search strategy and a flow diagram for the search


There was no duplicate study selection.




Table A2: Strengths and Limitations of Included Systematic Reviews Using AMSTAR4 Strengths Limitations

results were provided. A list of the included studies

and their characteristics were provided.




No conflict of interest was declared.


Shoulder

Longo 201411

There was triplicate study selection and data extraction.

A comprehensive literature search, including grey literature, was performed.

A flow diagram for the search results was provided.





No conflict of interest was declared.


A detailed search strategy was not provided.

A list of the excluded studies was provided.


AMSTAR = Assessment of Multiple Systematic Review s


APPENDIX 4: Main Study Findings and Authors Conclusions

Table A3: Summary of Findings of Included Systematic Reviews

Main Study Findings Authors Conclusions Ankle

VanTienderen 20176 Pain and Functional Outcomes

The mean AOFAS score, reported by three studies, improved from 48 to 80 between before and after the operation (p < 0.0005).

The mean FFI score, reported by one study, improved from 5.56 to 2.01 between before and after the operation (no p-value provided).

The mean VAS pain score, reported by three studies, improved from 7.1 to 2.7 between before and after the operation (p < 0.0005).

Patient Satisfaction Rates Across four studies, 70.5% of patients (i.e.,

62/88) reported good to excellent satisfaction with the operation.

Reoperation and Failure Rates

Across five studies, 25.3% of ankles (i.e., 23/91) required at least one reoperation, for a total of 28 operations. Reoperations included arthrodesis (i.e., ankle fusion) and arthroplasty (i.e., ankle replacement) on eight ankles. The most common indications for reoperations were development of moderate to severe osteoarthritis (14%), pain due to hardware (9%), extensive graft collapse (3%), and delayed or nonunion of osteotomy site (1%).

Across five studies, 13.2% of all operations (i.e., 12/91) were considered failures. Failures were defined as postoperative graft nonunion or resorption or persistence of symptoms leading to subsequent arthrodesis or arthroplasty.

Fresh bulk osteochondral allograft transplantation of the ankle can substantially improve functional status and effectively prevent or delay the eventual need for ankle arthrodesis or replacement. However, patients must be carefully selected and counselled on the morbidity of the procedure, as well as the high incidence of clinical failures and need for reoperations.

Pinski 20167

Pain and Functional Outcomes

The median AOFAS score, reported by 13 studies, was about 80 after the operation (data presented as bar graphs only).

Study Quality

The mean modified Coleman Methodology

Most studies reported good to excellent results from osteochondral allograft transplantation of the ankle.

Most studies reporting surgical treatment outcomes were of low levels of evidence and low methodological quality.


Table A3: Summary of Findings of Included Systematic Reviews Main Study Findings Authors Conclusions

Score for the 13 included studies was 55.1 on a scale of 100 and considered poor quality.

Knee

Assenmacher 20168


The mean HSS score, reported by three studies, was 84.1 after the operation.

The mean change was 23.1 in the KSS-F score (95% CI = 10.1 to 36.0, p < 0.01), 26.4 in the KSS-K score (95% CI = 10.4 to 42.4, p < 0.01), and 53 in the Lysholm score (95% CI = 27.4 to 78.6, p < 0.01) between before and after the operation, all indicating improvements.

Survival Rates The mean survival rate at 5, 10, 15, and

20 years after the operation, reported by three studies, was 94%, 84%, 71%, and 45%, respectively. The largest decrease in estimated survival occurred between the 15- and 20-year time-points.

Return-to-Activities Rates Across four studies, patients returned to

non-weight-bearing activities after a mean of 8.4 weeks following the operation. Patients returned to full activities, defined as clearance to return to sports, after a mean of 5.9 months following the operation.

Complication, Reoperation, and Failure Rates Across two studies, two cases of infection

after the operation were reported. One was deep infection, and the other was superficial cellulitis.

Across five studies, 36% of patients had reoperations. Reoperations included unicompartmental or total knee arthroplasty (37%), debridement (24%), graft removal, fixation, or revision (14%), symptomatic hardware removal (9%), meniscus surgery (6%), patellofemoral realignment procedures (3%), and ligament reconstruction (4%).

Across five studies, 25% of all operations were considered failures. Failures included conversion to unicompartmental (4%) or

Osteochondral allograft transplantation of the knee demonstrated significant improvements in clinical outcome scores and good durability with successful outcomes in the majority of the patients at 12.3 years after surgery.

The orthopaedic literature is limited by heterogeneity in surgical techniques, lesion and patient characteristics, and reporting of non-standardized outcome measures.



total (68%) knee arthroplasty and involved graft removal, fixation, or revision (28%).

Study Quality

The mean modified Coleman Methodology Score for the five included studies was considered fair quality.

Campbell 20169


One study reported that the KOOS ADL score improved from 62 to 82.82 between before and after the operation.

One study reported that the IKDC-S score improved from 46.27 to 79.29 between before and after the operation.

One study reported that the Marx score improved from 5.49 to 8.35 between before and after the operation

Return-to-Sports Rates One study reported that 88% of patients

had returned to sports by 30 months following the operation.

One study reported that 79% of patients had returned to preinjury-level performance by 9.6 months following the operation.

Complication and Reoperation Rates

One study reported that no events were identified.

Study Quality

The Coleman Methodology Score for the one included study was considered fair quality.

A high percentage of athletes have good clinical outcome scores after osteochondral allograft and may successfully return to athletic competition.

The athletes who had a better prognosis after surgery were younger and had a shorter preoperative duration of symptoms.

Krych 201610


The mean KOOS score, reported by three studies, improved from 18 to 46 between before and after the operation.

Return-to-Sports Rates

One study reported that return to sports at some level was 88% after the operation.

One study reported that the mean time to return to sports was 9.63.0 months after the operation.

Study Quality

The modified Coleman Methodology Score for the three included studies was considered fair quality.

A high rate of athletes can expect to return to sports following a chondral defect repair.



Chahal 20133 Pain and Functional Outcomes

The mean IKDC score, reported by six studies, improved from 37.1 to 64.3 between before and after the operation (p < 0.05).

The mean Lysholm score, reported by four studies, improved from 39.3 to 70.1 before and after the operation (p < 0.05).

The mean Tegner scale score, reported by three studies, improved from 3.9 to 5.5 before and after the operation (p < 0.05).

Survival Rates The mean survival rate at 5, 10, and 15 20

years after the operation, reported by two studies, was 91-95%, 76-85%, and 74-76%, respectively.

Patient Satisfaction Rates

Across five studies, 86% of patients reported being extremely or mostly satisfied with the operation.

Complication and Failure Rates

Across 19 studies, 2.4% of knees (i.e., 14/595) had short-term complications. The most common complications included removal of hardware, repeat arthroscopy, infections, deep vein thrombosis, hyperemic reaction, and early loosening of the graft.

Across 19 studies, 18% of knees (i.e., 108/595) had operations that were considered failures. Failures included total knee arthroplasty, revised or removed allograft, allograft fragmentation, arthrodesis, and amputation.

Study Quality

The modified Coleman Methodology Score for the 19 included studies was considered poor.

Osteochondral allograft transplantation for chondral defects of the knee results in predictably favourable outcomes and high satisfaction rates at intermediate follow-up.

Shoulder

Longo 201411


The mean Constant score, reported by three studies, was 76.2 after the operation.

According to one study, 0% of patients (i.e., 0/13) experienced recurrence of shoulder instability after the operation.

Even though osteochondral allograft reconstruction techniques had very low rates of recurrence, they had high rates of complications and low functional results.



According to two studies, the range of motion of the arm was restored or improved after the operation, compared to before the operation.

Complication Rates

According to three studies, 74% of patients (i.e., 17/23) had complications after the operation. Complications included spontaneous avascular necrosis and collapse, persistent pain, clicking, catching, stiffness, and flattening.

Study Quality

The mean modified Coleman Methodology Score for the three included studies was 71 on a scale of 100 and considered good quality.

ADL = activity of daily living; AOFAS = American Orthopaedic Foot and Ankle Society; CI = confidence interval; FFI = foot functional index; HSS = hospital for special surgery; IKDC = International Knee Documentation Committee; IKDC-S = International Knee

Documentation Committee-subjective; KOOS = knee injury and osteoarthritis outcome scale; KSS-F = Knee Society function score; KSS-K = Knee Society knee score; VAS = visual analog scale


APPENDIX 5: Additional References of Potential Interest

The following reviews were excluded from this report for the listed reasons but may be of interest to the readers. The methods used were not fully systematic. De Caro F, Bisicchia S, Amendola A, Ding L. Large fresh osteochondral allografts of the knee: a systematic clinical and basic science review of the literature. Arthroscopy. 2015 Apr;31(4):757-65. PubMed: PM25660010 Johnson P, Lee DK. Evidence-Based Rationale for Ankle Cartilage Allograft Replacement: A Systematic Review of Clinical Outcomes. J Foot Ankle Surg. 2015 Sep;54(5):940-3. PubMed: PM26028602 Ref ID: 63 RC0847 Saltzman BM, Riboh JC, Cole BJ, Yanke AB. Humeral Head Reconstruction With Osteochondral Allograft Transplantation. Arthroscopy. 2015 Sep;31(9):1827-34. PubMed: PM25979686 Vannini F, Buda R, Pagliazzi G, Ruffilli A, Cavallo M, Giannini S. Osteochondral Allografts in the Ankle Joint: State of the Art. Cartilage. 2013 Jul;4(3):204-13. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4297090 PubMed: PM26069666 The selection criteria included osteochondral allograft transplantation for the knee, but no randomized controlled studies fulfilling the criteria were found. Gracitelli GC, Moraes VY, Franciozi CE, Luzo MV, Belloti JC. Surgical interventions (microfracture, drilling, mosaicplasty, and allograft transplantation) for treating isolated cartilage defects of the knee in adults. Cochrane Database Syst Rev. 2016 Sep 3;9:CD010675. PubMed: PM27590275

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&list_uids=25660010&dopt=abstracthttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&list_uids=26028602&dopt=abstracthttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&list_uids=25979686&dopt=abstracthttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4297090http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&list_uids=26069666&dopt=abstracthttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&list_uids=27590275&dopt=abstract

Context and Policy IssuesResearch QuestionsKey FindingsMethodsLiterature Search MethodsSelection Criteria and MethodsExclusion CriteriaCritical Appraisal of Individual Studies

Summary of EvidenceQuantity of Research AvailableSummary of Study CharacteristicsSummary of Critical AppraisalSummary of FindingsLimitations

Conclusions and Implications for Decision or Policy MakingReferencesAppendix 1: Selection of Included StudiesAppendix 2: Characteristics of Included PublicationsAppendix 3: Critical Appraisal of Included PublicationsAppendix 4: Main Study Findings and Authors ConclusionsAppendix 5: Additional References of Potential Interest

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TITLE: The Use of Osteochondral Allograft for the Ankle, … · Seven systematic reviews (SRs) were found on clinical benefits and harms of osteochondral allograft transplantation