|Year : 2020 | Volume
| Issue : 1 | Page : 49-52
Study of percutaneous autologous bone marrow injections in delayed and nonunion of long bone fractures: A prospective study
Sidheshwar Thosar, Santosh Borkar, Prashant Kamath, Himaad Hullur, Raveena Kataria
Department of Orthopaedics, MIMER Medical College, Pune, Maharashtra, India
|Date of Submission||17-Jan-2020|
|Date of Acceptance||18-Sep-2020|
|Date of Web Publication||21-May-2021|
Dr. Santosh Borkar
Department of Orthopaedics, MIMER Medical College, Pune, Maharashtra
Source of Support: None, Conflict of Interest: None
Introduction: The potential benefit of human mesenchymal stem cells has received increasing attention in a wide variety of biomedical fields. The management of delayed union and non-union poses as a challenge to many orthopaedic surgeons. Bone marrow contains osteoprogenitor cells capable of forming bone.
Aims and Objectives: To observe the functional outcome, evaluate complications and assess the factors influencing results of bone marrow injection in long bone fractures which are in delayed union and non-union.
Methodology: We conducted prospective follow up study in orthopaedic department at tertiary care hospital over a period of two years. 30 patients with delayed or non-union of long bone fractures were included in the study About 20-50 ml of bone marrow was aspirated from single or both posterior iliac crests and injected into the recipient site under radiological control. Clinically patients were assessed and cortical bridging on AP and lateral X-rays was noted.
Results: In our study sex, age, state of union, initial treatment given before BMA, site of fracture, type of fracture, amount of bone marrow aspirate etc did not have any significant association with the final outcome after bone marrow injection. Also we did not get any significant complications.
Conclusion: Bone marrow injection from iliac crest (posterior) is safe, effective treatment method for delayed and non-union of long bone fractures without any significant complications.
Keywords: Bone marrow, fracture, injection, nonunion
|How to cite this article:|
Thosar S, Borkar S, Kamath P, Hullur H, Kataria R. Study of percutaneous autologous bone marrow injections in delayed and nonunion of long bone fractures: A prospective study. Duke Orthop J 2020;10:49-52
|How to cite this URL:|
Thosar S, Borkar S, Kamath P, Hullur H, Kataria R. Study of percutaneous autologous bone marrow injections in delayed and nonunion of long bone fractures: A prospective study. Duke Orthop J [serial online] 2020 [cited 2022 May 22];10:49-52. Available from: https://www.dukeorthojournal.com/text.asp?2020/10/1/49/316559
| Introduction|| |
Over a century ago, the German pathologist reported the existence of nonhemopoietic stem cells in bone marrow. His publication initiated the concept of bone marrow as source of fibroblasts that build collagen fibers and catalyze the process of wound healing. Recently, the potential benefit of human mesenchymal stem cells (MSC) has received increasing attention in a wide variety of biomedical fields.
Nonunion has been defined by the Food and Drug Administration as passage of 9 months since injury and the fracture showing no visible progressive sign of healing for the last 3 months. In delayed union, there is clinical and radiological evidence that healing is taking place but has not advanced at the average rate for that location and type of fracture. The management of delayed union and nonunion poses as a challenge to many orthopedic surgeons and represents a significant clinical problem. Mechanical techniques applied in order to enhance union include mechanical stimulation, electromagnetic fields, and low-intensity ultrasound. Biological techniques implemented to support and boost growth include osteoconductive biomaterials and osteoinductive factors. Osteoconductive materials consist of autologous bone graft, demineralized bone matrix, hydroxyapatite, and tricalcium phosphate. Licensed osteoconductive factors include bone morphogenic proteins either within the bone graft or from an exogenous source. Bone marrow contains osteoprogenitor cells capable of forming bone. Due to scarcity of data from India, we decided to conduct a prospective follow-up study to assess the efficacy of bone marrow injections in nonunion or delayed union of long bones.
Aims and objectives
The aim was to observe the functional outcome, evaluate complications, and assess the factors influencing results of bone marrow injection in long bone fractures which are in delayed union and nonunion.
| Materials and Methodology|| |
We conducted a prospective follow-up study in the orthopedic department at tertiary care hospital over a period of 2 years. Thirty patients with delayed or nonunion of long bone fractures were included in the study. Appropriate consent was obtained from patients, and ethical approval was acquired from the institute. Patients below the age of 18 years were excluded along with pathological fractures or hypertrophic nonunion.
Patients were placed in lateral or prone position under spinal anesthesia. About 20–50 ml of bone marrow was aspirated from single or both posterior iliac crests and injected into the recipient site under radiological control. Patients were discharged in 2–4 days and were followed up clinically and radiologically at intervals of 3 weeks, 6 weeks, 3 months, 6 months, and 9 months. Clinically, patients were assessed for tenderness, abnormal mobility, pain on weight-bearing, and radiologically for callus formation and cortical bridging on anterior-posterior and lateral X-rays.
Data were entered in Microsoft Excel, and statistical analysis was done in IBM SPSS Statistics for Windows, Version 21.0. (IBM Corp. Released 2012. Armonk, NY: IBM Corp). Data were expressed as mean and standard deviation for quantitative data and as frequency and percentages for qualitative data. Students' t-test was used for quantitative data and the Chi-square test for qualitative data. P < 0.005 was considered statistically significant.
| Results|| |
Among 30 patients, 24 were male. The age of patients varied between 26 and 28 years with a mean age of 46.5 years. The distribution of patients based on type and pattern of fracture was distributed as in [Table 1] and [Table 2].
Delayed union was seen among 26 patients (i.e., 86.7%), whereas nonunion was observed in 4 patients (13.3%). The state of union was not associated outcome of patients.
The distribution of patients according to initial treatment was as follows: casting 3.3%, closed intramedullary nailing (14) 46.7%, external fixation (3) 10%, and open plating (12) 40%. The association of initial treatment with the outcome was not significant.
There were 10 patients of femur fracture, 10 with tibia fracture, (P = 0.22) 3 patients with humerus fractures, 3 with radius fractures, and one patient with ulna fracture. There was no significant association between the site of fracture with treatment outcome (P = 0.23).
Out of 21 closed fractures, 16 showed union, 3 showed progression toward healing, and 2 showed nonunion. Out of 9 open fractures, 6 had achieved union, whereas 2 indicated progression toward union and 1 showed nonunion. The association of type of fracture with outcome was not statistically significant.
Out of 30, 14 out of 19 who received 30 ml or less united and 8 out of 11 who received > 30 ml united. The outcome associated with the quantity of bone marrow injection was not statistically significant (P = 0.41).
The clinical union was achieved with 13 patients at 3 months, 15 patients at 6 months, and with one patient at 9 months. The outcome was statistically significant (P = 0.008).
At 3 months, 2 patients had attained radiological union, whereas 17 patients reached radiological union at 6 months. The outcome was statistically significant (P < 0.01%).
The clinical union was gained early (18 weeks average), whereas radiological union was met at 22 weeks average.
| Discussion|| |
The management of nonunion is a challenge to many orthopedic surgeons and represents a significant clinical problem. Providing both mechanical and biological supports to the site of nonunion is of utmost importance. The biological stimuli for the regeneration of bone involve the interaction of osteoinductive growth signals, stem cells that respond to these signals, an intact vascular bed, and a scaffold that supports cellular proliferation and ingrowth. MSCs are believed to have multipotent plasticity with the capability to differentiate into a long multiple cell lineages such as cartilage, bone tendon, muscle, and nerve. Bone marrow is the most popular source of MSCs, and many surgeons had utilized unprocessed bone marrow aspirate (BMA) in an attempt to stimulate healing. Currently, BMA is most commonly obtained from the iliac crest. It is believed that the posterior iliac crest provides more connective tissue progenitors. Approximately 0.01% of the cells in BMA consist of MSCs with the total number of viable cells reducing with age. Hernigou et al. evaluated the outcome of BMA concentrates from the iliac crest for management atrophic nonunion of the tibia in 60 patients. Bone union was achieved in 88% of patients at 4 months.
In another recent study, Hernigou et al. reported the use of an injection of BMAC at the site of nonunion in 86 ankles in diabetic patients. The outcomes were compared to 86 diabetic-matched nonunions treated with bone graft harvested from the iliac crest. They found that BMAC resulted in healing in 82% of the ankles compared to only 62.3% in the control group with fewer complications in the BMAC groups. Ma et al. used bone marrow injection to promote healing in long bones and got good results.
Kassem also reported 95% union rate at 3 months in 20 patients with bone marrow aspiration concentrate. Harvesting BMAC is associated with potential risks such as microvascular injury (rare), infection, or rarely fat embolism., In our study, sex, age, state of union (nonunion or delayed union), initial treatment given before BMA, site of fracture, type of fracture (simple or compound), amount of BMA, etc., did not have any significant association with the final outcome after bone marrow injection. Furthermore, we did not get any significant complications in our study. Thus, our results were comparable to those in the literature.
However, our sample size was small, the study was nonrandomized, without any control group, and follow-up was only for a limited period.
| Conclusion|| |
Bone marrow injection from the iliac crest (posterior) is safe, effective treatment method for delayed and nonunion of long bone fractures without any significant complications which are encountered in open bone grafting. However, it can be used only for cases in which there is no angular deformity, shortening or unstable fixation at the nonunion site, as it has no mechanical advantage compared to bone graft technique. Our study sample size was small, and our study was a nonrandomized study without any control group. Hence, prospective randomized controlled clinical trials would be recommended before coming to any definite conclusion.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Connoly JF. Clinical use of marrow osteoprogenitor cells to stimulate osteogenesis. Clin Orthop Relat Res 1998;355:S257-66.
Pecina M, Vukicevics S. Biological aspects of bone, cartilage and tendon regeneration. Int Orthop 2007;31:719-20.
Calori GM, Mazza EL, Mazzola S, et al. Non-unions. Clin Cases Miner Bone Metab 2017;14:186-8. doi:10.11138/ccmbm/2017.14.1.186.
Metin U, Murat C, Murat B, Adnan K. Treatment of aseptic hypertrophic non union of the lower extremity with less invasive stabilization system (new approach to hypertrophic nonunion treatment). Adv Orthop Surg 2015;2015:631254.
Perren SM. Fracture healing: Fracture healing understood as the result od a fascinating cascade of physical and biological interactions. Part 1 an attempt to integrate observation from 30 years AO research. Acta Chir Orthop Traumatol Cechoslox 2014;81:355-64.
Emara KM, Diab RA, Emara AK. Recent biological trends in management of fracture non-union. World J Orthop 2015;6:623-8.
Emhon TA. Enhancement of fracture-healing. Instr Course Lect 1996;45:401-16.
Tiedmann JJ, Connolly JF, Strates BS, Lippiello L. Treatment of non-union by percutaneous injection of bone marrow and demineralised bone matrix. Clin Orthop Relat Res 1991;268:294-302.
Kevin B, Cleveland: Delayed and non-union of fractures. In: Campbell Text Book of Orthopaedics. 11th
ed. Philadelphia, PA, Elsevier/Mosby; 2010. p. 3529-64.
Carofin BC, Fieberman JR. Gene therapy application for fracture healing. J Bone Joint Surg Am 2008;90:99-110.
Hoch AI, Leach JK. Concise review. Optimising expansion of bone marrow mesenchymal stem/stromal cells for clinical applications. Stem Cells Transl Med 2014;3:643-52.
Sim R, Liang TS, Tay BK. Autologous marrow injection in the treatment of delayed and non-union of long bones. Singapore Med J 1993;34:412-7.
Emadedin M, Labibzadeh N, Fazel R, Mohseni F, Hosseini SE, Moghadasali R, et al
. Percutaneous stromal cell implantation is safe for reconstruction of human lower limb long bone atrophic non-union. Cell J 2017;19:159-65.
Hernigou P, Poignard A, Rouard H. Percutaneous autologous bone marrow grafting; influence of numbered concentrations of cells. J Bone Joint Surg 2005;87:1430-7.
Hernigou P, Guissou I, Homma V, Poignard A, Chevallier N, Rouard H, et al
. Percutaneous injection of bone marrow mesenchymal stem cells for ankle non unions decrease complications in patients with diabetes. Int Orthop 2015;39:1639-43.
Ma JT, Yu M, Zhang MC, Zhur XJ, Xu HY, Liang GJ. Clinical observation on percutaneous autologous bone marrow grafting for treatment of fracture non-union. Zhogguo Gu Shang 2009;22:862-4.
Kassem MS. Percutaneous autologous bone marrow injection for delayed union or non-union of fractures after internal fixation. Acta Orthop Belg 2013;79:711-7.
Hernigou J, Picard L, Alves A, Silvera J, Homma Y, Hernigou P. Understanding bone safety zones during bone marrow aspiration from the iliac crest: The sector rule. Int Othop 2014;38:2377-84.
Orlowski JP, Julius CJ, Petras RE, Povembka DT, Galagher JM. The safety of intraosseous infusions: Risks of fat and bone marrow emboli to the lungs. Ann Emerg Med 1989;18:1062-7.
[Table 1], [Table 2]