PERCUTANEOUS BONE MARROW ASPIRATE TRANSPLANTATION TREATMENT FOR NON-UNION OF LONG BONES FRACTURE

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1 Basrah Journal Of Surgery PERCUTANEOUS BONE MARROW ASPIRATE TRANSPLANTATION TREATMENT FOR NON-UNION OF LONG BONES FRACTURE Midhat M Mahdi *, Ali H Khudair # & Hamed * CABS Assist. Prof. of orthopedics, # FICMS Assist. Prof. of Orthopedics, Department of Surgery, College of Medicine, University of MB,ChB. IRAQ Abstract The search for simple and relatively low morbidity method for repair of bone derives its impetus from the perceived limitations of autologous bone grafting which has been the standard treatment for almost fifty years. One of these methods is by using autologous bone marrow grafting which is rich in osteoprogenitor cells to enhance the union in case of delay or nonunion. The aim of this study is to estimate the effectiveness of clinical application of the osteogenic marrow in the management of non-union of long bones fracture. This is a cross sectional study done at Basrah General Hospital, Orthopedic Department, between January 2009 to September 2011 on 24 patients (22 Males and 2 Females) with different types of non-union of long bones (3 humeri, 8 femurs and 13 tibiae). About 100 ml or more of bone marrow was aspirated from multiple sites of the iliac crest and injected percutaneously at the fracture site in the same session with-out centrifugation. In 21 out of 24 patients, union had been achieved with success rate of 87.5%. In three cases union was not achieved, one involving lower third of left tibia (Gustillo 3B), the second one is closed mid shaft tibial fracture and the third case middle third closed fracture of right femur. It is observed that percutaneous bone marrow grafting was relatively safe, simple, and some time reliable method of treating fracture non-union. It is a limited invasive technique with minimal complications. It is cost effective and potentially can avoid major surgical procedures and their morbidity. Introduction standard treatment for delayed Thealing and nonunion was open surgical fixation with autogenous bonegrafting. This provides essential elements for bone formation: osteoinduction, osteoconduction and osteoprogenitor cells. However, autogenous bone-grafting provides limited options and is associated with donor-site morbidity. Many other biological and biophysical approaches have been developed to minimize the occurrence of delayed union and nonunion 1. Biological approaches include: gene therapy, tissue engineering, osteoconductive biomaterials, growth factors, bone-marrow aspirates and osteocompetent cells. Physical forces include: mechanical stimulation by lowintensity ultrasound, electromagnetic fields, and extracorporeal shock wave therapy. There have also been recent studies on the impact of drugs and hormonal therapy, especially parathyroid hormone, on bone repair 1. Patients and methods This cross-sectional study was performed at Basrah General Hospital, Orthopedic Department, between January 2009 to September 2011 on 24 patients (22 males and 2 females) with different types of non-union of long bones, oligotrophic type in 13 patient (10 tibiae and 3 femurs ) and hypertrophic in 11 patients (3 humeri, 3 tibiae and 5 femurs). The fracture site is percutaneously drilled in different direction using 4.5 mm drill bit. After preparation of fracture site, the tract was 66

2 sutured to create a water tight compartment as possible. Bone marrow was aspirated from multiple sites of iliac crest by using trocar and sleeve inserted into outer table of iliac bone by gentle hammering. The trocar is then removed, leaving the sleeve fixed to the bone, then by using 2-3/50ml syringes, a gentle suction was applied. A total of 100 ml or slightly more of bone marrow were aspirated and then injected into and arround the fracture site through different directions using 18 gauges needle without centrifugation and no anticoagulation. In 4 patient plaster immobilization had been used (3 tibiae and 1 humerus), while in 20 patients external fixation (AO or Hoffman II type) had been applied (2 humeri, 8 femurs and 10 tibiae) before tackling the non-union site. Tourniquet was used and fibular osteotomy were done in four cases with non-union of tibia to correct the malalignment prior to fracture fixation.the patient was discharged on third postoperative day. We followed the patients both clinically and radiologically: Clinical evaluation includes evaluation for signs of compartment syndrome, fat embolism and infection (pin tract or osteomyelitis) by looking for redness, edema, discharge and local tenderness at fracture site which had been done every week for 4 weeks then every 4 weeks. Radiological evaluation had been requested on first postoperative day to assess the alignment and every 4 weeks to check union. We instructed our patients for nonweight bearing (4-6wks), then partial weight bearing for another (4wks) and assisted weight bearing then after. Dynamization of the external fixators were on 12th week. After 16 weeks the union was assessed clinically by loosening of the external fixator and checking for abnormal movements at the fracture site, if there is good signs of healing both radiologically and clinically the external fixator was removed on 16th week especially in humeral fractures. In cases with femoral or tibial fractures the period was extended longer and may reach up to 32 weeks. The treatment was regarded failed if excessive movement at fracture site is detected and no radiological signs of healing 16th week. Results Twenty two males (91.6%) and 2 females (8.4%) (24 patients), were included in this study. Their age ranged between years with average 37 years. In this study a higher percentage were due to road traffic accident 17 patients (70.83%), half of them had compound fractures with different degrees of soft tissue injuries (Gustillo classification) as shown in tables I&II. Table I: Mechanism of injury Types of injury Number Road traffic accident RTA 17 Bullet 4 Direct and Indirect Low Energy Force 3 24 Table II: Types of fractures Type of Fracture No. Closed fracture 12 Compound fracture 12 Gustillo1 4 Gustillo2 2 Gustillo3A 3 Gustillo3B 3 Gustillo3C 0 24 % % % 67

3 More than half of our patients (54.17%) had oligotrophic non-union while the remaining (45.83%) had hypertrophic non-union (Table III). Table III: Types of Non union Type of non-union Number % Atrophic or oligotrophic Hypertrophic % Tibial bone involved in 13 patients (54.17%), femur in 8 (33.3%) and humerus in 3 patients (12.5%) Table (IV). Table IV: Bone involved Site involved Number % Tibia Femur Humerus Twenty one out of twenty four patients had union in average of 4.5 months, with success rate of 87.5%. All 11 patients with hypertrophic non-union were healed by 8-20 weeks while 10 out of 13 atrophic & oligotrophic type were healed in weeks, in the other three patients with atrophic & oligotrophic non- union were failed to unite one involving lower third of left tibia (Gustillo.3B), the second one was closed mid shaft tibial fracture and the third case was closed middle third of right femur. Two methods of fixation were used, 20 patients (83.33%) were treated with external fixation compared to 4 patients (16.67%) treated with plaster immobilization. Three patients 12.5% complicated by infection. Two had pin tract infection (tibia) treated by antibiotic and local care, the infection had cured and the fracture united. The third one developed osteomyelitis of the femur treated with repeated drainage and antibiotic, failed to unite. Three patients 12.5% fail to unite one involving lower third of left tibia (Gustillo 3B), the second one is closed mid shaft tibial fracture and the third closed middle third fracture of femur. Table V: Complications following bone marrow grafting. Complication Number % Infection Non union Joint deformity Fat embolism 0 0% Compartment syndrome 0 0% Figure 1: (a) hypertrophic non-union of left tibia, (b) 2 weeks post-operative, (c) 1 month later, (d) 3month post treatment. 68

4 Figure 2: (a) non-union of left humerus with plate avulsion fixed in situ by external fixation with bone marrow injection, (b) 6 weeks and,(c)12 weeks post-operative. Figure 3: (a) oligotrophic non-union of right femur, (b) after stabilization by external fixation with bone marrow injection,(c) 8 weeks and,(d) 16weeks post injection. Discussion Whole marrow auto transplantation, with or without centrifugation, is simple safe effective technique with less possibility of contamination 2-4. It can be used as augmented bone marrow by combine it with ordinary autogenous bone cells, Kiel bone (composite xeno-autograft), ceramics (hydroxyapatite, tricalicium phosphate) and or fibrillar collagen. Marrow cells could be introduced in to cell culture and mesenchymal cells could be selected and mitotically expanded providing an appropriate number of cells to facilitate the repair process of massive bone defects. Impregnated allograft with bone marrow obtained from the host is the best way of ensuring the incorporation of foreign grafts 5-7. The results of present study regarding the achievement of union (87%) is not inferior to those achieved by Connolly in 1991 (90%) 4 and Rakesh Bhargava (82.1%) 8. The work of Paley et al showed experimentally that marrow produces optimal effect when used early in the fracture healing process, with the poorest results encountered with established nonunion 5. Healey 9 in his study of eight cases injected around 50 ml of marrow. Four of them were injected only once, while the remaining four cases were injected twice. The outcome was not significantly changed (87.5%). Connolly et al 4 injected around ml of marrow in their cases, in all their 20 cases they used only one injection with union rate 90% Garg et al 10 in their study injected ml of bone marrow at the fracture site twice at three weekly intervals with union rate (85%). It has also been shown that increasing concentration of marrow by centrifugation techniques increase its osteogenic activity 2,11. These techniques are extremely useful while using bone 69

5 marrow where the fracture site is relatively small and space is limited as the volume of injection largely depends upon the site of injection 2. In our study we apply a total of 100 ml or more of crude non-processed marrow injected once to non-union site because of limited facilities and equipments. Heparin was not required in our study because of the short interval between aspiration and injection, thereby avoiding the potential impairment of bone healing associated with heparin reported by F.Cantini et al 12. The risk factors that played a role in causing non-union still keeping their thumb print in those cases that failed to unite after bone marrow autotransplantation like high energy force, soft tissue loss, previous infection or poor blood supply as in lower third of tibia.in 3 patients (12.5%) the union is failed to achieve, in the first patient with compound fracture of lower third of tibia (Gustillo 3B), in the second patient with closed mid shaft fracture of tibia he gave a history of osteomyelitis during childhood and the skin over the fracture site is bad, the third case had mid shaft closed femoral fracture,in all three cases the type of non-union is atrophic. We think that the shortage of procedure required for concentrated bone marrow processing and sterilization, with some time fluoroscopy control to drill the fracture site in addition to local factors such as poor soft tissue cover and vascularity were the major factors of failure to achieve union. In conclusion bone marrow grafting is a relatively safe, simple, and reliable method of treating fracture non-union. It is a limited invasive technique with minimal complications. It is cost effective and potentially can avoid major surgical reconstruction. It has less morbidity than other sophisticated procedure of bone graft. It provides unlimited sources and can be repeated for several times. We recommend the use of concentrated bone-marrow by centrifugation in cell therapy unit to obtain a concentrated Buffy coat containing progenitor cells and other mononuclear cells. The use of image intensifier for better localization of nonunion site during drilling and injection.the selection of cases for this mode of management should have high selection bias. Further expanded clinical studies are necessary to evaluate this mode of treatment by increase the number of patients and availability of equipment and facility for cells separation. References 1- Wendy M. Novicoff, Abhijit Manaswi, MaCalus V. Hogan, Shawn M. Brubaker, William M. Mihalko and Khaled J. Saleh. Critical Analysis of the Evidence for Current Technologies in Bone-Healing and Repair. J Bone Joint Surg Am ;90: Connolly J, Royguse,Lippiello L and Dehene R,. Development of osteogenic bone marrow preparation. J.Bone and Joint Surgery1989;Vol.71A: 5 : Connolly J, Guse-R, Tiedeman J,Dehne R. Autologus bone marrow injection as a Substitute for operative grafting of tibial non union. Clinical Orthop ;MAY(266): R. Geoffery B urewell, Gary, E. Friedlaendov,Henny, J.Mankin. Current Perspectives and future directions. The 1983 Invitational conference on osteochondral allograft. Clinical Orthop. 1985; 197: Dror Paley et al.percutaneous bone marrow grafting of fractures and bony defect. Clinical Orthop. And Related Research 1986; 208: Seitz-HW. Jr, Froimson AL Leb. RB.Autogenous bone marrow and allograft replacement Of bone defects in the hand and upper extremities. J. Orthop. Trauma 1992;6(1) : Selvadurai Nayagam,David Warwik.orthopedic operation. In:Louis Solomon,Selvadurai Nayagam,David Warwik Apleys system of orthop. and fractures India 8th.ed Hodder Arnold 2001 ;12: Bhargava R, Sankhla SS, Gupta A, Changani RL, Gagal KC.Percutaneous autologus bone marrow injection in the treatment of delayed or nonunion. Indian J Orthop.2007;41: Healey JH, Zimmerman PA, McDonnell JM, Lane JM. Percutaneous bone marrow grafting of delayed union and nonunion in cancer patients. Clin Orthop Relat Res. 1990;256: Garg NK, Gauer S, Sharma S.Percutaneous bone marrow grafting in 20 cases of ununited fractures. Acta Orthop Scand 1993;64: Hernigou P, Poignard A, Beaujean F, Rouard H. Percutaneous autologous bone-marrow grafting for nonunions. Influence of number and concentration of progenitor cells. J Bone Joint Surg 2005;87-A: F.Cantini,L.Niccoli,F.Bellandi,O.Dimunno. Effects of short-term,high dose,heparin therpy on Biochemical Markers of bone metabolism.clincal rheumatology 1995;14 N6: