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ORIGINAL ARTICLE
Year : 2014  |  Volume : 27  |  Issue : 4  |  Page : 632-635

Bone marrow injection in treatment of long bone nonunion


Department of Orthopedic Surgery, Faculty of Medicine, Menoufiya University, Menoufiya, Egypt

Date of Submission06-Nov-2014
Date of Acceptance17-Dec-2014
Date of Web Publication22-Jan-2015

Correspondence Address:
Ahmed Abd Elfattah Khalil
Orthopedic Department, El Menshawy Hospital, Tanta
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1110-2098.149627

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  Abstract 

Objectives
The goal of this study was to report the role of bone marrow injection in treatment of nonunited long bones fractures and to evaluate the relationship between bony union and bone marrow.
Background
Bone marrow injection has been used for the management of fracture nonunion since a long period of time. The main advantages for this technique are: it can be used in patient unfit for open grafting, is safe, uses osteogenic cells, has no complications in graft site, and can prevent nonunion development. Other advantages include: it is simple, quick, inexpensive, and causes minimal surgical trauma.
Patients and methods
From November 2009 to February 2013, 20 patients, 16 male patients and four female patients, mean age 36.5 years, suffering from nonunited lower limb fractures were treated in the Orthopedic Department, El-Menoufiya University Hospital by bone marrow injection in site of fracture nonunion.
Results
Of the 20 patients who had bone marrow injection for nonunion, 16 (80%) patients achieved union and four (20%) patients failed to achieve union. Of the four patients who were not healed, one patient had received three bone marrow injections, whereas three patients had received four bone marrow injections.
Conclusion
In our study, the patient's age and smoking were inversely proportional to healing after bone marrow injection. In addition, patients who had closed fracture at the time of initial injury achieved union more than patients who had open fracture at the time of initial injury.

Keywords: Long bone fracture, non-union, bone marrow injection


How to cite this article:
Elsattar TA, Alseedy AI, Khalil AA. Bone marrow injection in treatment of long bone nonunion. Menoufia Med J 2014;27:632-5

How to cite this URL:
Elsattar TA, Alseedy AI, Khalil AA. Bone marrow injection in treatment of long bone nonunion. Menoufia Med J [serial online] 2014 [cited 2020 Feb 27];27:632-5. Available from: http://www.mmj.eg.net/text.asp?2014/27/4/632/149627


  Introduction Top


Bone marrow contains a population of rare progenitor cells capable of differentiating into osteoblasts, chondrocytes, adipocytes, and muscle cells [1]. The osteogenic capabilities of bone marrow prompted surgeons to begin using it as a bone graft material. Hernigou et al. treated 20 nonunited tibial fractures by injecting freshly harvested bone marrow into tibial defects and resulted in clinical and radiological union [2]. The relationship between bony union and bone marrow is as follows: some of the cells of the callus originate in bone marrow and bone marrow cells are responsible for the formation of part of the bony callus [3]. Bone marrow stem cells develop into hematopoietic and nonhematopoietic stem cells or marrow stromal cells, which are progenitors of skeletal tissue components such as bone and cartilage, as well as blood components [4]. Autologous bone graft (autograft) is the most efficient method used to treat fracture nonunions and occasionally to treat acute fractures with bone defects. Traditionally, autologous bone is harvested from the iliac crest; this could result in significant pain and morbidity. Alternatively, allografts, autogenous bone marrow injection, and synthetic bone substitutes can be used [5]. In our study, grafting with autologous bone marrow can obtain healing of nonunions. Bone marrow from the iliac crest have long been the most prevalent and effective method of cell transplantation. We treated 20 patients with nonunited lower limb fractures by simple closed bone marrow injection into fracture site and 16 patients showed clinical and radiological union.

In this study, we investigated the efficiency of autogenous bone marrow injection in the treatment of nonunion fractures.


  Patients and methods Top


Twenty patients, 16 male patients and four female patients, with nonunion were treated with bone marrow injection between November 2009 and February 2013. In all, 14 (70%) patients had their nonunion in the right side, whereas the other six (30%) patients affected the left side. The mean age of the patients was 36.5 years (range 10-63 years). According to the type of original fractures, five of the 20 patients had originally open fractures. Initial treatment at the time of marrow injection included the following: four patients had been fixed with cast, four with plates and screws, seven patients with intramedullary locking nails, three patients with Ilizarov external fixators, one patient with uniplanar external fixator, and one patient with gliding intramedullary nail. Only four (20%) patients had a past history of presence of infection in the site of nonunion.

Marrow aspiration and injection needles were used in this study. C-arm was used for detection of the nonunited fracture site and insertion of those needles into their proper position. First, trimming and refreshing of the fracture edges closed is performed under guidance of C-arm by needles. Thereafter, aspiration of bone marrow was performed from anterior superior iliac spine with another needle and the aspirated marrow was injected simultaneously into the injection needles inserted into the nonunion site. Postoperative care after bone marrow graft injection includes internal or external fixation (for the open fractures) or plaster cast immobilization (for the closed fractures) after bone marrow grafting. Non-weight-bearing was advised for 1 month postoperative. Patients were asked to review every 2 weeks in the first month and then every month at the outpatient clinic for clinical and radiological assessment.

Statistical analysis

The statistical analysis was conducted using SPSS version 16.0 (SPSS Inc., Chicago, Illinois, USA). A P value of less than 0.05 was considered to be statistically significant.


  Results Top


Our obtained results revealed that healing was mostly affected significantly by the patient age as shown in [Table 1]. As indicated in [Table 2], of 20 bone marrow injected patients, two patients received two injections and both were healed, 11 patients received three injections (10 patients of them were healed), and seven patients received four injections (four patients of them were healed). In addition, there is a direct proportion between age and number of injections - that is, there is increased age with increase of number of injections [Table 2]. Moreover, of six patients who were smokers, three (50%) achieved healing, whereas the other three (50%) smokers failed to show union after marrow injections as represented in [Table 3]. Of patients (n = 6) who had their nonunion in the femur, four patients healed after marrow injections and two patients failed to heal, whereas of 14 patients who had their injury in the tibia, 12 patients healed and two patients failed to achieve union [Table 4]. In addition, of 12 patients who had closed fracture at the time of initial injury, 11 patients achieved union and only one patient failed to achieve union, whereas of eight patients who had open fracture at the time of initial injury, five patients achieved union and three patients failed to heal after marrow injection [Table 5].
Table 1: The relationship between healing after bone marrow injection and age

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Table 2: The relationship between the age and the number of injections for healed and nonhealed patients

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Table 3: The effect of smoking on healing after marrow injection

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Table 4: The relationship between the site of nonunion (femur and tibia) and healing

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Table 5: The relationship between type of fracture (open or closed) and healing

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Final result (healing rate after marrow injection) revealed that, of the 20 patients who had bone marrow injection for nonunion, 16 (80%) patients achieved union and four (20%) patients failed to achieve union. Of the four patients who were not healed, one patient had received three bone marrow injections, whereas three patients had received four bone marrow injections. Overall results were excellent in 13 patients, good in three, fair in one, and poor in three patients. Union occurred in 16 patients. The mean ± SD healing time for healed patients after bone marrow injection (according to radiographic data) was 85.875 ± 2.927 days.


  Discussion Top


There is no universally accepted definition of nonunion of a fracture. It is known that every given type of fracture tends to unite within a certain time period. If the fracture fails to heal within the time usually required for it and it will never unite without intervention, it is called nonunion [6]. Bone marrow injection neither promotes healing more rapidly nor more effectively compared with standard operative grafting. However, it has many distinct advantages over the standard operative grafting. First, the complications at the donor and recipient sites are significantly diminished. Second, it can be performed in cases that are not fit for open bone grafting because of the poor condition of the skin. Third, it can be repeated easily. Fourth, it utilizes the most osteogenic cells of a bone graft and does not introduce devitalized tissue (dead bone) and this could be used in children without damaging the growth plate. Sixth, it can be performed under local anesthesia and avoids the risks of general anesthesia or can be used for patients with contraindication for general anesthesia. Seventh, it can be used for certain clinical situations that would not be strong enough indications for open bone grafting, such as delayed union or fractures prone to delay union. Eighth, it is safe. Ninth, it is practical and time saving, as it can be performed on an outpatient basis and decreases hospital stay. Tenth, it is cost effective [7]. However, bone marrow injection has some disadvantages; these include the lack of providing immediate mechanical stability as well as the risk of dilution with peripheral blood [7]. In the present study, the mean age of the patients was 37.667 years; this was close to the studies by Sim et al. [8], 38 years, and El Hussieny [9], 38 years, whereas in the study of Connolly et al. [10] it was 34 years, Arazi et al. [11], 34.3 years, Siwach et al. [12], 41.2 years, and 42 years in the study by Willkins [13]. This result is in agreement with the statement of Muschler et al. [14] that age is not only influencing the number of the nucleated cells, but also influencing the prevalence of osteoblastic progenitors harvested from human bone marrow by aspiration technique [15]. In our study, we had 20 patients with the incidence of 80% : 20% male-to-female ratio; this was close to the studies by Connolly et al. [10] who had 70% : 30%, Jean et al. [16] who had 71.4% : 28.6%, and El Hussieny [9] who had 74% : 26%, in contrast to 57.2% : 42.8% male-to-female ratio in the study of Matsuda et al. [17], Sim et al. [8] who had 90% : 10%, and 56.1% : 43.9% male-to-female ratio in study by Willkins [6]. Our results indicated that, of the patients (n=6) who were smokers, three (50%) achieved healing, whereas the other three (50%) smokers failed to show union after marrow injections. Similar results were observed by Reynders and Broos [18] who had mentioned a highly significant relationship between smoking and persistence of nonunion. The technique used in this study was similar to the technique described by Connolly et al. [19], Sebecic et al. (20), and Siwach et al. [12], in respect to percutaneous aspiration of the marrow and its simultaneous injection in the nonunion site under fluoroscopic control [Figure 1],[Figure 2] and [Figure 3].
Figure 1: Preoperative radiograph.

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Figure 2: Immediate intraoperative radiograph by C-arm.

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Figure 3: Postoperative follow-up radiograph.

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  Conclusion Top


In our study, the patient's age and smoking were inversely proportional to healing after bone marrow injection. In addition, patients who had closed fracture at the time of initial injury achieved union more than patients who had open fracture at the time of initial injury.


  Acknowledgements Top


Conflicts of interest

There are no conflicts of interest.[20]

 
  References Top

1.
Noshi T, Yoshikawa T, Dohi Y, Ikeuchi M, Horiuchi K, Ichijima K, et al. Recombinant human bone morphogenetic protein-2 potentiates the in vivo osteogenic ability of marrow/hydroxyapatite composites. Artif Organs 2001; 25 :201-208.  Back to cited text no. 1
    
2.
Hernigou P, Poignard A, Manicom O, Mathieu G, Rouard H. The use of percutaneous autologous bone marrow transplantation in nonunion and avascular necrosis of bone. J Bone Joint Surg 2005; 87-B :896-902.  Back to cited text no. 2
    
3.
Brighton CT, Hunt RM. Early histological and ultrastructural changes in medullary fracture callus. J Bone Joint Surg Br 1991; 73-A :832-847.  Back to cited text no. 3
    
4.
Jensen GS, Kandel RR, Stanford WL. The use of in situ bone marrow stem cells for the treatment of various degenerative diseases. J Med Hypoth 2002; 59 :422-428.  Back to cited text no. 4
    
5.
Marsh D. Concepts fracture union, delayed union, and nonunion. Clin Orthop 1998; 355s :22-30.  Back to cited text no. 5
    
6.
Willkins R. Percutaneous treatment of long nonunions. The use of autologous bone marrow and allograft bone matrix. J Orthop 2003;112-114.  Back to cited text no. 6
    
7.
Fleming D. Bone cell and matrices in orthopaediac tissue engineering. J Orthop Clin North Am 2000; 31 :357-375.  Back to cited text no. 7
    
8.
Sim R, Liang TS, Tay BK. Autologous marrow injection in the treatment of delayed and nonunion in long bones. Singapore Med J 1993; 34 :412-417.  Back to cited text no. 8
    
9.
El Hussieny TF. Percutaneous bone marrow auto transplantation in nonunion of long bone. Pan Arab J Orthop Trauma 1998; 2 :127-135.  Back to cited text no. 9
    
10.
Connolly J, Guse R, Lippiello L, Dehni I. Development of an osteogenic bone-marrow preparation. J Bone Joint Surg 1989; 71-A :684-691.  Back to cited text no. 10
    
11.
Arazi M, Oegun T, Mutlu M, Ertlu A. Percutaneous autogenous bone marrow injection in delayed union and non union of long bone fractures: a preliminary report. Acta Orthop Traumatol Turc 2000; 34 :267-272.  Back to cited text no. 11
    
12.
Siwach RC, Sangwan SS, Singh R, Goel A. Role of percutaneous bone marrow grafting in delayed unions, nonunions and poor regenerates. Indian J Med Sci 2001; 55 :326-336.  Back to cited text no. 12
    
13.
Willkins R. Percutaneous treatment of long nonunions. The use of autologous bone marrow and allograft bone matrix. J Orthop 2003;112-114.  Back to cited text no. 13
    
14.
Muschler GF, Nitto H, Boehm CA, Easley KA. Age and gender related changes in the cellularity of human bone marrow and the prevalence of osteoblastic progenitors. J Orthop Res 2001; 19 :117-125.  Back to cited text no. 14
    
15.
Muschler G, Majors A, Bohem C, Nitto H, Midura R. Characterization of human bone marrow stromal cells with respect to osteoblastic differentiation. J Bone Joint Surg 1997; 79-A :546-557.  Back to cited text no. 15
    
16.
Jean JL, Tang HL, Wang SJ, Chang JH, Lin SC, Chen CJ, et al. Efficacy of autologous percutaneous bone marrow graft injection for treatment of nonunion of the tibia. Formosan J Surg 2001; 34 :294-301.  Back to cited text no. 16
    
17.
Mastuda Y, Sakayama K, Okumura H, Kawatani Y, Mashima N, Shibata T. Percutaneous autologous bone marrow transplantation for nonunion of the femur. Arch Jpn Chir 1998; 67 :10-18.  Back to cited text no. 17
    
18.
Reynders P, Broos P. Percutaneous injection of autogenous bone marrow in delayed union of tibia and femur. J Bone Joint Surg 2004;86-90.  Back to cited text no. 18
    
19.
Connolly J, Roy G, Jeffreyt I, Rober TD. Autologous marrow injection as a substitute for operative grafting of tibial nonunions. Clin Orthop 1991; 266 :259-270.  Back to cited text no. 19
    
20.
Sebecic B, Gabelica V, Patyrlj L, Sosa T. Percutaneous autologous bone marrow grafting on the site of tibial delayed union. Croat Med J 1999; 40 :429-432.  Back to cited text no. 20
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]


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Introduction
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