Skip to main content
Erschienen in: International Orthopaedics 11/2017

13.08.2017 | Review Article

A systematic review of the clinical applications and complications of bone marrow aspirate concentrate in management of bone defects and nonunions

verfasst von: Mohamed A. Imam, James Holton, Lukas Ernstbrunner, Wojciech Pepke, Florian Grubhofer, Ali Narvani, Martyn Snow

Erschienen in: International Orthopaedics | Ausgabe 11/2017

Einloggen, um Zugang zu erhalten

Abstract

Purpose

Fracture healing encompasses a succession of dynamic multifactorial metabolic events, which ultimately re-establishes the integrity of the biomechanical properties of the bone. Up to 10% of the fractures occurring annually will need additional surgical procedures because of impaired healing. The aim of this article is to review the current literature regarding the use of bone marrow aspirate concentrate (BMAC) and its effectiveness in the management of bone defects.

Methods

We have included all published clinical literature investigating the development, techniques and applications of BMAC. Language, design and risk of bias did not deter the initial inclusion of any study. Our search was exclusively limited to studies involving human subjects. A PRISMA compliant search was carried out as published in 2009. This included the online databases: PubMed, EMBASE, clinical trial.​gov and the Cochrane library from 1960 to the end of May 2015. MeSH terms used included: “Bone” AND “Marrow” AND “Aspirate” AND “Concentrate” AND “Bone Defects” AND “NONUNION”. Eligible studies were independently appraised by two authors using the Critical Appraisal Skills Program checklist. For the purpose of narrative review, relevant studies were included irrespective of methodology or level of evidence.

Results

Thirty-four of the 103 (48 PubMed and 55 EMBASE) results yielded by the preliminary search were included. Exclusions included three duplicate records, six letters, 17 non-orthopaedics related studies and four records irrelevant to our search topic. The CASP appraisal confirmed a satisfactory standard of 31 studies. They all had clearly defined objectives, were well designed and conducted appropriately to meet them. The published studies reported the use of BMAC in non-union and fracture healing (15 studies), bone defects (nine studies), spine fusion (two studies), distraction osteogensis (two studies) and complications related to the use of BMAC (seven studies).

Conclusions

Stem cells found in BMAC have the potential to self-renew, undertake clonal expansion and differentiate into different musculoskeletal tissues. The commercial processing of BMAC needs to be optimized in order to achieve a consistent end product, which will provide predicable and translatable results. The future potential of cell characterization in order to determine the optimum cell for repair/regeneration of bone also needs to be explored.
Level of Evidence: Systematic Review of minimum level IV studies.
Literatur
1.
2.
Zurück zum Zitat Einhorn TA (1996) Enhancement of fracture healing. Instr Course Lect 45:401–416PubMed Einhorn TA (1996) Enhancement of fracture healing. Instr Course Lect 45:401–416PubMed
3.
Zurück zum Zitat Einhorn TA (1998) The cell and molecular biology of fracture healing. Clin Orthop Relat Res 355(Suppl):S7–21CrossRef Einhorn TA (1998) The cell and molecular biology of fracture healing. Clin Orthop Relat Res 355(Suppl):S7–21CrossRef
4.
Zurück zum Zitat Health Quality Ontario (2005) Osteogenic protein-1 for long bone nonunion: an evidence-based analysis. Ont Health Technol Assess Ser 5(6):1–57 Health Quality Ontario (2005) Osteogenic protein-1 for long bone nonunion: an evidence-based analysis. Ont Health Technol Assess Ser 5(6):1–57
6.
Zurück zum Zitat Hannouche D, Petite H, Sedel L (2001) Current trends in the enhancement of fracture healing. J Bone Joint Surg Br 83(2):157–164CrossRefPubMed Hannouche D, Petite H, Sedel L (2001) Current trends in the enhancement of fracture healing. J Bone Joint Surg Br 83(2):157–164CrossRefPubMed
7.
Zurück zum Zitat Perren SM (2014) Fracture healing: fracture healing understood as the result of a fascinating cascade of physical and biological interactions. Part I. An attempt to integrate observations from 30 years AO research. Acta Chir Orthop Traumatol Cechoslov 81(6):355–364 Perren SM (2014) Fracture healing: fracture healing understood as the result of a fascinating cascade of physical and biological interactions. Part I. An attempt to integrate observations from 30 years AO research. Acta Chir Orthop Traumatol Cechoslov 81(6):355–364
9.
Zurück zum Zitat Stevenson S (1998) Enhancement of fracture healing with autogenous and allogeneic bone grafts. Clin Orthop Relat Res 355(Suppl):S239–S246CrossRef Stevenson S (1998) Enhancement of fracture healing with autogenous and allogeneic bone grafts. Clin Orthop Relat Res 355(Suppl):S239–S246CrossRef
10.
Zurück zum Zitat Baksh D, Song L, Tuan RS (2004) Adult mesenchymal stem cells: characterization, differentiation, and application in cell and gene therapy. J Cell Mol Med 8(3):301–316CrossRefPubMed Baksh D, Song L, Tuan RS (2004) Adult mesenchymal stem cells: characterization, differentiation, and application in cell and gene therapy. J Cell Mol Med 8(3):301–316CrossRefPubMed
11.
Zurück zum Zitat Gulotta LV, Kovacevic D, Ehteshami JR, Dagher E, Packer JD, Rodeo SA (2009) Application of bone marrow-derived mesenchymal stem cells in a rotator cuff repair model. Am J Sports Med 37(11):2126–2133. doi:10.1177/0363546509339582 CrossRefPubMed Gulotta LV, Kovacevic D, Ehteshami JR, Dagher E, Packer JD, Rodeo SA (2009) Application of bone marrow-derived mesenchymal stem cells in a rotator cuff repair model. Am J Sports Med 37(11):2126–2133. doi:10.​1177/​0363546509339582​ CrossRefPubMed
12.
Zurück zum Zitat Nejadnik H, Hui JH, Feng Choong EP, Tai BC, Lee EH (2010) Autologous bone marrow-derived mesenchymal stem cells versus autologous chondrocyte implantation: an observational cohort study. Am J Sports Med 38(6):1110–1116. doi:10.1177/0363546509359067 CrossRefPubMed Nejadnik H, Hui JH, Feng Choong EP, Tai BC, Lee EH (2010) Autologous bone marrow-derived mesenchymal stem cells versus autologous chondrocyte implantation: an observational cohort study. Am J Sports Med 38(6):1110–1116. doi:10.​1177/​0363546509359067​ CrossRefPubMed
13.
Zurück zum Zitat Imam MA, Mahmoud SSS, Holton J, Abouelmaati D, Elsherbini Y, Snow M (2017) A systematic review of the concept and clinical applications of bone marrow aspirate concentrate in orthopaedics. SICOT-J 3:17CrossRef Imam MA, Mahmoud SSS, Holton J, Abouelmaati D, Elsherbini Y, Snow M (2017) A systematic review of the concept and clinical applications of bone marrow aspirate concentrate in orthopaedics. SICOT-J 3:17CrossRef
16.
Zurück zum Zitat Hernigou P, Poignard A, Manicom O, Mathieu G, Rouard H (2005) The use of percutaneous autologous bone marrow transplantation in nonunion and avascular necrosis of bone. J Bone Joint Surg Br Vol 87(7):896–902. doi:10.1302/0301-620X.87B7.16289 CrossRef Hernigou P, Poignard A, Manicom O, Mathieu G, Rouard H (2005) The use of percutaneous autologous bone marrow transplantation in nonunion and avascular necrosis of bone. J Bone Joint Surg Br Vol 87(7):896–902. doi:10.​1302/​0301-620X.​87B7.​16289 CrossRef
17.
Zurück zum Zitat Kassem MS (2013) Percutaneous autogenous bone marrow injection for delayed union or non union of fractures after internal fixation. Acta Orthop Belg 79(6):711–717PubMed Kassem MS (2013) Percutaneous autogenous bone marrow injection for delayed union or non union of fractures after internal fixation. Acta Orthop Belg 79(6):711–717PubMed
18.
20.
Zurück zum Zitat Jager M, Jelinek EM, Wess KM, Scharfstadt A, Jacobson M, Kevy SV, Krauspe R (2009) Bone marrow concentrate: a novel strategy for bone defect treatment. Curr Stem Cell Res Ther 4(1):34–43CrossRefPubMed Jager M, Jelinek EM, Wess KM, Scharfstadt A, Jacobson M, Kevy SV, Krauspe R (2009) Bone marrow concentrate: a novel strategy for bone defect treatment. Curr Stem Cell Res Ther 4(1):34–43CrossRefPubMed
21.
Zurück zum Zitat Muschler GF, Nitto H, Matsukura Y, Boehm C, Valdevit A, Kambic H, Davros W, Powell K, Easley K (2003) Spine fusion using cell matrix composites enriched in bone marrow-derived cells. Clin Orthop Relat Res 407:102–118CrossRef Muschler GF, Nitto H, Matsukura Y, Boehm C, Valdevit A, Kambic H, Davros W, Powell K, Easley K (2003) Spine fusion using cell matrix composites enriched in bone marrow-derived cells. Clin Orthop Relat Res 407:102–118CrossRef
22.
Zurück zum Zitat McCarrel T, Fortier L (2009) Temporal growth factor release from platelet-rich plasma, trehalose lyophilized platelets, and bone marrow aspirate and their effect on tendon and ligament gene expression. J Orthop Res 27(8):1033–1042. doi:10.1002/jor.20853 CrossRefPubMed McCarrel T, Fortier L (2009) Temporal growth factor release from platelet-rich plasma, trehalose lyophilized platelets, and bone marrow aspirate and their effect on tendon and ligament gene expression. J Orthop Res 27(8):1033–1042. doi:10.​1002/​jor.​20853 CrossRefPubMed
23.
Zurück zum Zitat Wilkins RM, Kelly CM (2003) The effect of allomatrix injectable putty on the outcome of long bone applications. Orthopedics 26(5 Suppl):s567–s570PubMed Wilkins RM, Kelly CM (2003) The effect of allomatrix injectable putty on the outcome of long bone applications. Orthopedics 26(5 Suppl):s567–s570PubMed
24.
Zurück zum Zitat Fortier LA, Potter HG, Rickey EJ, Schnabel LV, Foo LF, Chong LR, Stokol T, Cheetham J, Nixon AJ (2010) Concentrated bone marrow aspirate improves full-thickness cartilage repair compared with microfracture in the equine model. J Bone Joint Surg Am 92(10):1927–1937. doi:10.2106/JBJS.I.01284 CrossRefPubMed Fortier LA, Potter HG, Rickey EJ, Schnabel LV, Foo LF, Chong LR, Stokol T, Cheetham J, Nixon AJ (2010) Concentrated bone marrow aspirate improves full-thickness cartilage repair compared with microfracture in the equine model. J Bone Joint Surg Am 92(10):1927–1937. doi:10.​2106/​JBJS.​I.​01284 CrossRefPubMed
28.
Zurück zum Zitat Siwach RC, Sangwan SS, Singh R, Goel A (2001) Role of percutaneous bone marrow grafting in delayed unions, non-unions and poor regenerates. Indian J Med Sci 55(6):326–336PubMed Siwach RC, Sangwan SS, Singh R, Goel A (2001) Role of percutaneous bone marrow grafting in delayed unions, non-unions and poor regenerates. Indian J Med Sci 55(6):326–336PubMed
29.
Zurück zum Zitat Matsuda Y, Sakayama K, Okumura H, Kawatani Y, Mashima N, Shibata T (1998) Percutaneous autologous bone marrow transplantation for nonunion of the femur. Nihon Geka Hokan 67(1):10–17PubMed Matsuda Y, Sakayama K, Okumura H, Kawatani Y, Mashima N, Shibata T (1998) Percutaneous autologous bone marrow transplantation for nonunion of the femur. Nihon Geka Hokan 67(1):10–17PubMed
30.
Zurück zum Zitat Garg NK, Gaur S, Sharma S (1993) Percutaneous autogenous bone marrow grafting in 20 cases of ununited fracture. Acta Orthop Scand 64(6):671–672CrossRefPubMed Garg NK, Gaur S, Sharma S (1993) Percutaneous autogenous bone marrow grafting in 20 cases of ununited fracture. Acta Orthop Scand 64(6):671–672CrossRefPubMed
31.
Zurück zum Zitat Hernigou P, Mathieu G, Poignard A, Manicom O, Beaujean F, Rouard H (2006) Percutaneous autologous bone-marrow grafting for nonunions. Surgical technique. J Bone Joint Surg Am 88(Suppl 1 Pt 2):322–327. doi:10.2106/JBJS.F.00203 CrossRefPubMed Hernigou P, Mathieu G, Poignard A, Manicom O, Beaujean F, Rouard H (2006) Percutaneous autologous bone-marrow grafting for nonunions. Surgical technique. J Bone Joint Surg Am 88(Suppl 1 Pt 2):322–327. doi:10.​2106/​JBJS.​F.​00203 CrossRefPubMed
33.
Zurück zum Zitat Hernigou P, Guissou I, Homma Y, Poignard A, Chevallier N, Rouard H, Flouzat Lachaniette CH (2015) Percutaneous injection of bone marrow mesenchymal stem cells for ankle non-unions decreases complications in patients with diabetes. Int Orthop. doi:10.1007/s00264-015-2738-2 Hernigou P, Guissou I, Homma Y, Poignard A, Chevallier N, Rouard H, Flouzat Lachaniette CH (2015) Percutaneous injection of bone marrow mesenchymal stem cells for ankle non-unions decreases complications in patients with diabetes. Int Orthop. doi:10.​1007/​s00264-015-2738-2
35.
Zurück zum Zitat Hernigou P, Beaujean F (2002) Treatment of osteonecrosis with autologous bone marrow grafting. Clin Orthop Relat Res 405:14–23CrossRef Hernigou P, Beaujean F (2002) Treatment of osteonecrosis with autologous bone marrow grafting. Clin Orthop Relat Res 405:14–23CrossRef
36.
Zurück zum Zitat Jager M, Herten M, Fochtmann U, Fischer J, Hernigou P, Zilkens C, Hendrich C, Krauspe R (2011) Bridging the gap: bone marrow aspiration concentrate reduces autologous bone grafting in osseous defects. J Orthop Res 29(2):173–180. doi:10.1002/jor.21230 CrossRefPubMed Jager M, Herten M, Fochtmann U, Fischer J, Hernigou P, Zilkens C, Hendrich C, Krauspe R (2011) Bridging the gap: bone marrow aspiration concentrate reduces autologous bone grafting in osseous defects. J Orthop Res 29(2):173–180. doi:10.​1002/​jor.​21230 CrossRefPubMed
37.
Zurück zum Zitat Hernigou P, Poignard A, Beaujean F, Rouard H (2005) Percutaneous autologous bone-marrow grafting for nonunions. Influence of the number and concentration of progenitor cells. J Bone Joint Surg Am 87(7):1430–1437. doi:10.2106/JBJS.D.02215 PubMed Hernigou P, Poignard A, Beaujean F, Rouard H (2005) Percutaneous autologous bone-marrow grafting for nonunions. Influence of the number and concentration of progenitor cells. J Bone Joint Surg Am 87(7):1430–1437. doi:10.​2106/​JBJS.​D.​02215 PubMed
38.
Zurück zum Zitat Petri M, Namazian A, Wilke F, Ettinger M, Stubig T, Brand S, Bengel F, Krettek C, Berding G, Jagodzinski M (2013) Repair of segmental long-bone defects by stem cell concentrate augmented scaffolds: a clinical and positron emission tomography--computed tomography analysis. Int Orthop 37(11):2231–2237. doi:10.1007/s00264-013-2087-y CrossRefPubMedPubMedCentral Petri M, Namazian A, Wilke F, Ettinger M, Stubig T, Brand S, Bengel F, Krettek C, Berding G, Jagodzinski M (2013) Repair of segmental long-bone defects by stem cell concentrate augmented scaffolds: a clinical and positron emission tomography--computed tomography analysis. Int Orthop 37(11):2231–2237. doi:10.​1007/​s00264-013-2087-y CrossRefPubMedPubMedCentral
39.
Zurück zum Zitat Sauerbier S, Rickert D, Gutwald R, Nagursky H, Oshima T, Xavier SP, Christmann J, Kurz P, Menne D, Vissink A, Raghoebar G, Schmelzeisen R, Wagner W, Koch FP (2011) Bone marrow concentrate and bovine bone mineral for sinus floor augmentation: a controlled, randomized, single-blinded clinical and histological trial--per-protocol analysis. Tissue Eng A 17(17–18):2187–2197. doi:10.1089/ten.TEA.2010.0516 CrossRef Sauerbier S, Rickert D, Gutwald R, Nagursky H, Oshima T, Xavier SP, Christmann J, Kurz P, Menne D, Vissink A, Raghoebar G, Schmelzeisen R, Wagner W, Koch FP (2011) Bone marrow concentrate and bovine bone mineral for sinus floor augmentation: a controlled, randomized, single-blinded clinical and histological trial--per-protocol analysis. Tissue Eng A 17(17–18):2187–2197. doi:10.​1089/​ten.​TEA.​2010.​0516 CrossRef
40.
Zurück zum Zitat Rickert D, Sauerbier S, Nagursky H, Menne D, Vissink A, Raghoebar GM (2011) Maxillary sinus floor elevation with bovine bone mineral combined with either autogenous bone or autogenous stem cells: a prospective randomized clinical trial. Clin Oral Implants Res 22(3):251–258. doi:10.1111/j.1600-0501.2010.01981.x CrossRefPubMed Rickert D, Sauerbier S, Nagursky H, Menne D, Vissink A, Raghoebar GM (2011) Maxillary sinus floor elevation with bovine bone mineral combined with either autogenous bone or autogenous stem cells: a prospective randomized clinical trial. Clin Oral Implants Res 22(3):251–258. doi:10.​1111/​j.​1600-0501.​2010.​01981.​x CrossRefPubMed
41.
Zurück zum Zitat Kitoh H, Kitakoji T, Tsuchiya H, Mitsuyama H, Nakamura H, Katoh M, Ishiguro N (2004) Transplantation of marrow-derived mesenchymal stem cells and platelet-rich plasma during distraction osteogenesis--a preliminary result of three cases. Bone 35(4):892–898. doi:10.1016/j.bone.2004.06.013 CrossRefPubMed Kitoh H, Kitakoji T, Tsuchiya H, Mitsuyama H, Nakamura H, Katoh M, Ishiguro N (2004) Transplantation of marrow-derived mesenchymal stem cells and platelet-rich plasma during distraction osteogenesis--a preliminary result of three cases. Bone 35(4):892–898. doi:10.​1016/​j.​bone.​2004.​06.​013 CrossRefPubMed
42.
Zurück zum Zitat Hendrich C, Franz E, Waertel G, Krebs R, Jager M (2009) Safety of autologous bone marrow aspiration concentrate transplantation: initial experiences in 101 patients. Orthop Rev 1(2):e32. doi:10.4081/or.2009.e32 CrossRef Hendrich C, Franz E, Waertel G, Krebs R, Jager M (2009) Safety of autologous bone marrow aspiration concentrate transplantation: initial experiences in 101 patients. Orthop Rev 1(2):e32. doi:10.​4081/​or.​2009.​e32 CrossRef
43.
47.
Zurück zum Zitat Burkle CM, Harrison BA, Koenig LF, Decker PA, Warner DO, Gastineau DA (2004) Morbidity and mortality of deep sedation in outpatient bone marrow biopsy. Am J Hematol 77(3):250–256. doi:10.1002/ajh.20185 CrossRefPubMed Burkle CM, Harrison BA, Koenig LF, Decker PA, Warner DO, Gastineau DA (2004) Morbidity and mortality of deep sedation in outpatient bone marrow biopsy. Am J Hematol 77(3):250–256. doi:10.​1002/​ajh.​20185 CrossRefPubMed
49.
50.
Zurück zum Zitat Hernigou J, Picard L, Alves A, Silvera J, Homma Y, Hernigou P (2014) Understanding bone safety zones during bone marrow aspiration from the iliac crest: the sector rule. Int Orthop 38(11):2377–2384. doi:10.1007/s00264-014-2343-9 CrossRefPubMed Hernigou J, Picard L, Alves A, Silvera J, Homma Y, Hernigou P (2014) Understanding bone safety zones during bone marrow aspiration from the iliac crest: the sector rule. Int Orthop 38(11):2377–2384. doi:10.​1007/​s00264-014-2343-9 CrossRefPubMed
52.
Zurück zum Zitat Orlowski JP, Julius CJ, Petras RE, Porembka DT, Gallagher JM (1989) The safety of intraosseous infusions: risks of fat and bone marrow emboli to the lungs. Ann Emerg Med 18(10):1062–1067CrossRefPubMed Orlowski JP, Julius CJ, Petras RE, Porembka DT, Gallagher JM (1989) The safety of intraosseous infusions: risks of fat and bone marrow emboli to the lungs. Ann Emerg Med 18(10):1062–1067CrossRefPubMed
Metadaten
Titel
A systematic review of the clinical applications and complications of bone marrow aspirate concentrate in management of bone defects and nonunions
verfasst von
Mohamed A. Imam
James Holton
Lukas Ernstbrunner
Wojciech Pepke
Florian Grubhofer
Ali Narvani
Martyn Snow
Publikationsdatum
13.08.2017
Verlag
Springer Berlin Heidelberg
Erschienen in
International Orthopaedics / Ausgabe 11/2017
Print ISSN: 0341-2695
Elektronische ISSN: 1432-5195
DOI
https://doi.org/10.1007/s00264-017-3597-9

Weitere Artikel der Ausgabe 11/2017

International Orthopaedics 11/2017 Zur Ausgabe

Arthropedia

Grundlagenwissen der Arthroskopie und Gelenkchirurgie. Erweitert durch Fallbeispiele, Videos und Abbildungen. 
» Jetzt entdecken

Update Orthopädie und Unfallchirurgie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.