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Limited evidence in support of bone marrow aspirate concentrate as an additive to the bone marrow stimulation for osteochondral lesions of the talus: a systematic review and meta-analysis

Knee Surgery, Sports Traumatology, Arthroscopy (2023)Cite this article

Abstract

Purpose

Bone marrow aspirate concentrate can be used as an additive to surgical treatment of osteochondral lesions of the talus. This systematic literature review aims to study the effect of the additional use of bone marrow aspirate concentrate on top of a surgical treatment for osteochondral lesions of the talus on clinical outcomes compared to surgical treatment alone.

Methods

An online literature search was conducted using PubMed (Medline), Embase (Ovid), and the Cochrane library for all studies comparing a surgical intervention with bone marrow aspirate concentrate, with a surgical intervention without bone marrow aspirate concentrate. The methodological quality was rated according to the methodological index for non-randomised studies checklist. The primary outcome measure were clinical outcomes. Secondary outcome measures consisted of revision rate, complication rate, radiographic outcome measures and histological analyses. Subgroups were created based on type of surgical intervention used in the studies. If multiple articles were included in a subgroup, a linear random-effects model was used to compare the bone marrow aspirate concentrate-augmented group with the control group.

Results

Out of 1006 studies found, eight studies with a total of 718 patients were included. The methodological quality, assessed according to the methodological index for non-randomised studies checklist, was weak. A significantly better functional outcome measures (p < 0.05) was found in the subgroup treated with bone marrow stimulation + bone marrow aspirate concentrate compared to the group treated with bone marrow stimulation alone, based on three non-blinded studies. No significant differences regarding clinical outcomes were found in the subgroups comparing matrix-induced autologous chondrocyte implantation with matrix-induced bone marrow aspirate concentrate, osteochondral autologous transplantation alone with osteochondral autologous transplantation + bone marrow aspirate concentrate and autologous matrix-induced chondrogenesis plus peripheral blood concentrate vs. matrix-associated stem cell transplantation bone marrow aspirate concentrate.

Conclusion

There is insufficient evidence to support a positive effect on clinical outcomes of bone marrow aspirate concentrate as an additive to surgical treatment of osteochondral lesions of the talus. However, based on the safety reports and initial results, sufficiently powered, patient- and researcher-blinded, prospective randomised controlled trials are justified and recommended. Until then, we advise not to implement a therapy (addition of bone marrow aspirate concentrate) without clinical evidence that justifies the additional costs involved.

Level of evidence

Level III.

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Fig. 1
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Fig. 3

Data availability

Not available.

Abbreviations

ACI:

Autologous chondrocyte implantation

AMIC:

Autologous matrix-induced chondrogenesis

AOFAS:

American Orthopaedic Foot and Ankle Society

BMAC:

Bone marrow aspirate concentrate

BMI:

Body mass index

BMP:

Bone morphogenetic protein

BMS:

Bone marrow stimulation

CI:

Confidence interval

CT:

Computer tomography

FAOS:

Foot ankle outcome score

ICRS:

International cartilage repair society

JACI:

Juvenile allogenic chondrocyte implantation

MAST:

Matrix-associated stem cell transplantation

mACI:

Matrix-induced autologous chondrocyte implantation

mBMAC:

Matrix-induced bone marrow aspirate concentrate

MINORS:

Methodological index for non-randomised studies

MOCART:

Magnetic resonance observation of cartilage repair tissue

MRI:

Magnetic resonance imaging

MSC:

Mesenchymal stem cell

n.r.:

Not reported

OAT:

Osteochondral autologous transplantation

OCL:

Osteochondral lesion

OLT:

Osteochondral lesion of the talus

PBC:

Peripheral blood concentrate

PDGF:

Platelet-derived growth factor

PRF:

Platelet-rich fibrin

PRISMA:

Preferred reporting items for systematic reviews and meta-analysis

PROM:

Patient-reported outcome measure

PROSPERO:

International prospective register of systematic reviews

SD:

Standard deviation

SF-12:

Short form survey 12

TGF-ß:

Transforming growth factor-beta

VAS:

Visual analogue scale

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Acknowledgements

The authors would like to thank AMC’s clinical librarian, F. Jamaludin for her contribution to the present systematic review.

Funding

No funding was received for this study.

Author information

Authors and Affiliations

  1. Department of Orthopedic Surgery and Sports Medicine, Amsterdam Movement Sciences, Amsterdam UMC, Location AMC, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands

    Chiel Klein, Jari Dahmen, Kaj S. Emanuel, Sjoerd Stufkens & Gino M. M. J. Kerkhoffs

  2. Academic Center for Evidence Based Sports Medicine (ACES), Amsterdam UMC, Amsterdam, The Netherlands

    Chiel Klein, Jari Dahmen, Kaj S. Emanuel, Sjoerd Stufkens & Gino M. M. J. Kerkhoffs

  3. Amsterdam Collaboration for Health and Safety in Sports (ACHSS), International Olympic Committee (IOC) Research Center, Amsterdam UMC, Amsterdam, The Netherlands

    Chiel Klein, Jari Dahmen, Kaj S. Emanuel, Sjoerd Stufkens & Gino M. M. J. Kerkhoffs

Authors
  1. Chiel Klein
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  2. Jari Dahmen
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  3. Kaj S. Emanuel
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  4. Sjoerd Stufkens
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  5. Gino M. M. J. Kerkhoffs
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Corresponding author

Correspondence to Gino M. M. J. Kerkhoffs.

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Not applicable (systematic review and meta-analysis).

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Appendices

Appendix 1

21–6-2022:

Databases:

  

PubMed, Embase (Ovid), Cochrane Library

Before deduplication

After deduplication

Total

971

633

PUBMED

375 hits:

("Ankle"[Mesh] OR "Ankle Joint"[Mesh] OR "Ankle Injuries"[Mesh] OR "Talus"[Mesh] OR ankle*[tiab] OR talus[tiab] OR talar*[tiab])

AND

("Osteochondritis"[Mesh] OR "Osteochondritis Dissecans"[Mesh] OR "Cartilage, Articular"[Mesh] OR osteochondritis dissecans[tiab] OR osteochondrosis dissecans[tiab] OR osteochondrolysis[tiab] OR osteochondriti*[tiab] OR osteochondral[tiab] OR chondral[tiab] OR transchondral[tiab] OR cartilage*[tiab] OR OCD[tiab] OR OLT[tiab] OR OCL[tiab])

AND

("Bone Marrow"[Mesh] OR "Bone Marrow Transplantation"[Mesh] OR "Bone Marrow Cells"[Mesh] OR bone marrow[tiab] OR BMAC[tiab] OR BMA[tiab] OR BMC[tiab] OR aspirat*[tiab] OR concentrat*[tiab])

EMBASE (OVID):

Database(s): Embase Classic + Embase 1947 to 2022 June 20

Search Strategy:

#

Searches

Results

1

exp ankle/ or talus/ or ankle injury/

53,992

2

(ankle* or talus or talar*).ti,ab,kf

102,927

3

1 or 2

111,150

4

osteochondritis/ or osteochondritis dissecans/ or articular cartilage/

41,385

5

(osteochondritis dissecans or osteochondrosis dissecans or osteochondrolysis or osteochondriti* or osteochondral or chondral or transchondral or cartilage* or OCD or OLT or OCL).ti,ab,kf

166,699

6

4 or 5

175,272

7

exp bone marrow/ or exp bone marrow transplantation/

344,567

8

(bone marrow or BMAC or BMA or BMC or aspirat* or concentrat*).ti,ab,kf

3,295,583

9

7 or 8

3,408,032

10

3 and 6 and 9

575

Cochrane Library:

Cochrane Database of Systematic Reviews

Issue 6 of 12, June 2022

0 hits

Cochrane Central Register of Controlled Trials

Issue 5 of 12, May 2022

21 hits

IDSearchHits

#1(ankle* or talus or talar*):ti,ab,kw11215

#2(osteochondritis dissecans or osteochondrosis dissecans or osteochondrolysis or osteochondriti* or osteochondral or chondral or transchondral or cartilage* or OCD or OLT or OCL):ti,ab,kw6316

#3(bone marrow or BMAC or BMA or BMC or aspirat* or concentrat*):ti,ab,kw176136

#4#1 and #2 and #321

UPDATE 21–6-2022 t/m 13-3-2023

13–3-2023:

Databases:

  

PubMed, Embase (Ovid), Cochrane Library

Before deduplication

After deduplication

Total

85

35

PUBMED

375 hits:

("Ankle"[Mesh] OR "Ankle Joint"[Mesh] OR "Ankle Injuries"[Mesh] OR "Talus"[Mesh] OR ankle*[tiab] OR talus[tiab] OR talar*[tiab])

AND

("Osteochondritis"[Mesh] OR "Osteochondritis Dissecans"[Mesh] OR "Cartilage, Articular"[Mesh] OR osteochondritis dissecans[tiab] OR osteochondrosis dissecans[tiab] OR osteochondrolysis[tiab] OR osteochondriti*[tiab] OR osteochondral[tiab] OR chondral[tiab] OR transchondral[tiab] OR cartilage*[tiab] OR OCD[tiab] OR OLT[tiab] OR OCL[tiab])

AND

("Bone Marrow"[Mesh] OR "Bone Marrow Transplantation"[Mesh] OR "Bone Marrow Cells"[Mesh] OR bone marrow[tiab] OR BMAC[tiab] OR BMA[tiab] OR BMC[tiab] OR aspirat*[tiab] OR concentrat*[tiab])

AND ("2022/06/21"[Date—Publication]: "2023/03/13"[Date—Publication])

EMBASE (OVID):

Database(s): Embase Classic + Embase 1947 to 2023 March 10

Search Strategy:

#

Searches

Results

1

exp ankle/ or talus/ or ankle injury/

58,008

2

(ankle* or talus or talar*).ti,ab,kf

109,084

3

1 or 2

118,341

4

osteochondritis/ or osteochondritis dissecans/ or articular cartilage/

43,039

5

(osteochondritis dissecans or osteochondrosis dissecans or osteochondrolysis or osteochondriti* or osteochondral or chondral or transchondral or cartilage* or OCD or OLT or OCL).ti,ab,kf

175,085

6

4 or 5

183,887

7

exp bone marrow/ or exp bone marrow transplantation/

358,192

8

(bone marrow or BMAC or BMA or BMC or aspirat* or concentrat*).ti,ab,kf

3,438,133

9

7 or 8

3,554,438

10

3 and 6 and 9

616

11

limit 10 to yr = "2022 -Current"

54

Cochrane Library:

Cochrane Central Register of Controlled Trials

Issue 2 of 12, February 2023

4 results

Cochrane Database of Systematic Reviews

Issue 3 of 12, March 2023

0 results

IDSearchHits

#1(ankle* or talus or talar*):ti,ab,kw12405

#2(osteochondritis dissecans or osteochondrosis dissecans or osteochondrolysis or osteochondriti* or osteochondral or chondral or transchondral or cartilage* or OCD or OLT or OCL):ti,ab,kw6856

#3(bone marrow or BMAC or BMA or BMC or aspirat* or concentrat*):ti,ab,kw184484

#4#1 and #2 and #3 with Cochrane Library publication date Between Jun 2022 and Mar 20,234

Appendix 2

All Extracted patient demographics in the control group

Author

Intervention

N

Female

age

Previous trauma

Previous surgery

Symptoms (months)

Lesion area (mm2)

Lesion depth (mm)

Follow-up (months)

BMI

Medial location

Lateral location

Buda et al. (2015)

mACI

40

15 (37.5%)

31.4 ± 7.6

30 (75%)

15 (37.5%)

n.r.

170 ± 60

4.0 ± 0.9

48.0

n.r.

33 (82.5%)

7 (17.5%)

Desando et al. (2017)

mACI

7

3 (42.9%)

31.2 ± 8

n.r

n.r.

n.r.

180 ± 70

n.r

36.0

n.r.

n.r.

n.r.

Giannini et al. (2010)

mACI

46

Combined

34 (42.0%)

31.4 ± 7.6

100%

n.r.

n.r.

160 ± 60

Combined

4.0 ± 0.9

57.5 ± 14.5

n.r.

35 (76.1%)

7 (15.2%)

Hannon et al. (2015)

BMS

12

5 (41.7%)

39 ± 10.5

8(66.7%)

n.r.

14.4(2–60)

111.2 ± 25.9

n.r.

77.3 ± 13.5

n.r.

7 (58.3%)

5 (41.7%)

Murphy et al. (2019)

BMS

52

11 (21.2%)

39.7 ± 9.5

n.r

n.r.

n.r.

n.r.

n.r.

58.0

n.r.

47.0%

53.0%

Richter et al. (2019)

AMIC + PBC

129

52 (40%)

35.6 ± 13.8

62(48%)

n.r.

n.r.

n.r.

n.r.

23.8 ± 0.8

n.r.

n.r.

n.r.

Shimozono et al. (2018)

OAT

26

9 (34.6%)

33.6 ± 12.3

n.r.

n.r.

28.8 ± 17.9

102.5 ± 42.0

n.r

92.8 ± 13.8

n.r.

16 (61.5%)

10 (38.5%)

Tahta et al. (2017)

BMS

52

n.r

30.4 ± 7.6

n.r.

n.r.

n.r.

210 ± 40

6 ± 3

40.1 ± 3.2

25.3 ± 3.6

n.r.

n.r.

  1. n number, mm2 squared millimetre, mm millimetre, BMI body mass index, n.r. not reported, mACI matrix-induced autologous chondrocyte implantation, BMS bone marrow stimulation, AMIC autologous matrix-induced chondrogenesis, PBC peripheral blood concentrate, OAT osteochondral autologous implantation

All Extracted patient demographics in the intervention group

Author

Intervention

N

Female

Age

Previous trauma

Previous surgery

Symptoms (months)

Lesion area (mm2)

Lesion depth (mm)

Follow-up (months)

BMI

Medial location

Lateral location

Buda et al. (2015)

mBMAC

40

13 (32.5%)

30.2 ± 9.7

31 (77.5%)

17 (42.5%)

n.r.

180 ± 60

4.2 ± 0.9

48.0

n.r.

30 (75%)

10 (25%)

Desando et al. (2017)

mBMAC

15

5 (33.3%)

31 ± 7.8

n.r.

n.r.

n.r.

180 ± 70

n.r.

36.0

n.r.

n.r.

n.r.

Giannini et al. (2010)

mBMAC

25

Combined

34 (42%)

28.2 ± 9.4

100%

n.r.

n.r.

218 ± 50

Combined

4.0 ± 0.9

39.2 ± 1.9

n.r.

n.r.

n.r.

Hannon et al. (2015)

BMS + BMAC

22

9 (40.9%)

35 ± 14

17 (77.3%)

n.r.

14.7 (1–60)

103.0 ± 42.4

n.r.

48.3 ± 12.0

n.r.

12 (54.5%)

10 (45.5%)

Murphy et al. (2019)

BMS + BMAC

49

10 (22.4%)

34.6 ± 11.5

n.r.

n.r.

n.r.

n.r.

n.r.

40.0

n.r.

55.0%

45.0%

Richter et al. (2019)

BMAC

129

53 (41%)

35.3 ± 12.8

64 (50%)

n.r.

n.r.

n.r.

n.r.

24.4 ± 1.0

n.r.

n.r.

n.r.

Shimozono et al. (2018)

OAT + BMAC

28

7 (25%)

36.0 ± 15.3

n.r.

n.r.

23.0 ± 13.3

108.5 ± 43.3

n.r.

84.2 ± 10.5

n.r.

22 (78.6%)

6 (21.4%)

Tahta et al. (2017)

BMS + BMAC

46

n.r

28.8 ± 6.2

n.r.

n.r.

n.r.

190 ± 30

8 ± 2

42.2 ± 2.2

24.2 ± 4.3

n.r.

n.r.

  1. n number, mm2 squared millimetre, mm millimetre, BMI body mass index, n.r. not reported, mBMAC matrix-induced bone marrow aspirate concentrate, BMS bone marrow stimulation, BMAC bone marrow aspirate concentrate, OAT osteochondral autologous transplantation.

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Klein, C., Dahmen, J., Emanuel, K.S. et al. Limited evidence in support of bone marrow aspirate concentrate as an additive to the bone marrow stimulation for osteochondral lesions of the talus: a systematic review and meta-analysis. Knee Surg Sports Traumatol Arthrosc (2023). https://doi.org/10.1007/s00167-023-07651-1

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