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Effect of pulsed electromagnetic field on mandibular fracture healing: A randomized control trial, (RCT)
J Stomatol Oral Maxillofac Surg 120 (2019) 390–396
Available online at
ScienceDirect www.sciencedirect.com
Original Article
Effect of pulsed electromagnetic field on mandibular fracture healing: A randomized control trial, (RCT) H. Mohajerani a, F. Tabeie b, F. Vossoughi c, E. Jafari d, M. Assadi d,* a
Department of Oral and Maxillofacial Surgery, School of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran, Iran Department of Nuclear Medicine, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran c Department of Oral and Maxillofacial Surgery, School of dentistry, Hormozgan University of Medical Sciences, Bandar Abbas, Iran d The Persian Gulf Nuclear Medicine Research Center, Bushehr University Of Medical Sciences, Bushehr, Iran b
A R T I C L E I N F O
A B S T R A C T
Article history: Received 12 February 2018 Accepted 25 February 2019 Available online 2 March 2019
Introduction: Currently, the pulsed electromagnetic field (PEMF) method is utilized for the treatment of nonunion long bone fractures. Considering the established effect of the PEMF on the acceleration of the bone healing process, we conducted this study to evaluate the effect of PEMF on the healing process in mandibular bone fractures. Material and methods: : This research was a randomized control trial (RCT) study. The sample consisted of patients with a mandibular fracture who were hospitalized in order to receive closed reduction treatment. The participants were randomly selected and then sequentially divided into two groups of 16 participants each (controls = 16, cases = 16). The patients in the control group received conventional therapy without any extra treatment, while the patients in the case group received PEMF therapy in addition to conventional therapy. For the PEMF therapy, patients in the case group received immediate post-surgery PEMF therapy for 6 h. Next, they received 3 h of exposure for the next 6 d, and finally, the same process was repeated for 1.5 h for post-surgery days 8–13. The maxillomandibular fixation (MMF) device was removed at post-surgery week 4. The patients in the control group, however, did not receive any extra treatment. The efficiency of the treatment modalities was evaluated clinically and radiographically. For the radiographical assessment, we employed a direct digital panoramic machine to calculate the computerized density of the bone, and those measurements were used for comparison of the results between the control group and the study patients. Results: There was no significant difference in the mean bone density values between the two groups (P > 0.05). However, the percentage of changes in bone density of the two groups revealed that the case group had insignificant decreases at post-surgery day 14 and a significant increase at post-surgery day 28 compared with the control group (P < 0.05). After releasing the MMF, a bimanual mobility test of the fractured segments showed the stability of the segments in all patients. In the case group, the mouth opening was significantly more stable than that of the control group (P < 0.05). Conclusion: PEMF therapy postoperatively leads to increased bone density, faster recovery, increased formation of new bone, a further opening of the mouth, and decreased pain.
C 2019 Elsevier Masson SAS. All rights reserved.
Keywords: Pulsed electromagnetic fields Bone density Mandibular fracture Bone healing Pain management
1. Introduction The mandible is the most common bone in the jaw that is injured in facial trauma. Although the mandible is the largest and strongest facial bone, fractures are quite common, and in the middle region of the face, they occur two to three times more often than in other parts of the face [1].
* Corresponding author. E-mail address: [email protected] (M. Assadi). https://doi.org/10.1016/j.jormas.2019.02.022 C 2019 Elsevier Masson SAS. All rights reserved. 2468-7855/
The basic treatment principles for mandibular fracture include reduction, fixation, immobilization, and supportive therapies. Reduction can be attained with two procedures, which include the closed and open techniques. In the closed reduction technique, the fracture site is not surgically exposed, and the reduction is obtained with palpation of the bony fragments and restoration of the dental occlusion. Open reduction includes exposure of the fracture region to allow direct observation, validation of the procedure, and direct insertion of a fixation device at the fracture site [2].
H. Mohajerani et al. / J Stomatol Oral Maxillofac Surg 120 (2019) 390–396
Open reduction was found to be more popular than closed reduction among surgeons. However, the closed technique is still a valuable option when considering treatment of mandibular fracture [3]. In closed reduction, there is no threat of surgical morbidity, hospitalization, and the high cost of open reductions [4]. However, the long period of immobilization required and the subsequent delay of rehabilitation are significant limitations of the closed technique [5]. In pharmacological studies, a range of items, such as the regional use of growth factors, calcium sulfate, bone morphogenetic proteins [6], systemic reception of vitamin D, parathyroid hormone, estrogen, and base phosphonates, were evaluated for increasing the speed of fracture healing [7]. Other treatment procedures, including electrical, mechanical, and magnetic stimulation, the use of shock waves, hyperbaric oxygen treatment, and noninvasive ultrasound, were also evaluated for increasing the speed of fracture healing [8]. In the last decade, among the reported treatment procedures, the use of the biophysical intervention of pulsed electromagnetic field (PEMF) therapy was considered because it is a noninvasive, convenient, and easy to use intervention [9,10]. In 1970, the pulsed magnetic field was developed as a beneficial instrument for fracture regeneration. Although the mechanism of its action was unknown, it caused the effective regeneration of nonunion bone fractures [11]. In theory, PEMF offers a number of advantages, such as reactivation of the biological procedure of bone regeneration, simplification of fracture regeneration, and a shortened duration of treatment. In addition, some studies reported that PEMF has a positive effect on bone regeneration with certain energy transmission settings. These studies were commonly performed on long bones and vertebral bones [12]. However, PEMF is still not fully understood; therefore, one of the aims of this study was evaluation of the effect of the pulsed magnetic field on the regeneration process in patients with mandibular fracture. Also, as mentioned, since the most significant limitation of closed reduction is the need for a long period of immobilization, an additional aim of this study was the evaluation of the effect of PEMF on reducing this period.
2. Material and methods 2.1. Participants and study design This study was a randomized clinical trial project conducted among candidate patients for closed reduction treatment hospitalized with a mandibular fracture in the oral, jaw, and facial surgery
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department of a tertiary university-affiliated hospital in Tehran, Iran. The sampling method was by census. In the studied population, 16 patients were in the control group, and 16 patients underwent PEMF treatment. Inclusion criteria included the patient’s consent to participate in the study, a mandibular fracture in the dental region, the possibility of the application of an arch bar and maxillary mandibular fixation (MMF), absence of signs of infection in the fracture region, lack of systemic diseases affecting favorable stages of bone regeneration, and treatment indications of closed reduction. Exclusion criteria included lack of consent to participate in the study and contraindications of closed reduction treatment. Postoperatively, all of the patients received 1 g cefazolin and 8 mg of dexamethasone intravenously and 5 mg of morphine sulfate intramuscularly. For closed reduction, the region of the mandibular fracture underwent reduction manually, and after closing the arch bar, MMF was established in the patients with 24gauge wire (Fig. 1). Then, using the block randomization method in the form of foursome block and non-blind, all the patients were randomly divided into two groups, which included cases (16 patients) and controls (16 patients). The case group was exposed to PEMF, while the control group was not exposed to any radiation, and the device was turned off for them. The PEMF device was a portable unit that consisted of a coil and a magnetic field generator source along with a power supply source-generated PEMF with 1 millitesla (mT) intensity and 40 Hz frequency. The coil was fixed in the fracture zone (Fig. 2). The protocol for exposure to the PEMF was as follows: immediately post-surgery for 6 h with the intensity of 1 mT and a frequency of 40 Hz; three hours daily for the next 6 d (days 2–7) post-surgery with the intensity of 1 mT and a frequency of 40 Hz; 1.5 hours daily for the next 6 d (days 8–13) after operation with the intensity of 1 mT and a frequency of 40 Hz. MMF was opened in the case group after 4 weeks and in the control group after 6 weeks post-surgery. Patients were followed up on the day of surgery, and 7, 14, and 28 d post-surgery. Patient pain, sensory changes in the fracture region, the maximum amount of mouth opening, displacement of the fracture region, infection, and malocclusion of the fracture region were evaluated at each visit. The Visual Analog Scale (VAS) was used for pain measurement and rated from 1–10. On this scale, 0, 1–3, 4–7, and 8–10 were considered as no pain, slight pain, moderate pain, and severe pain, respectively. Patient verbal affirmation of abnormal lip sensation was used for evaluation of sensory changes along with a questionnaire that had been completed by the patients. In this
Fig. 1. A patient who underwent maxillary mandibular fixation (MMF) (A) and pulsed electromagnetic field (PEMF) therapy.
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images, Dfw 2.7 is capable of measuring the bone density in the fracture site by measurement of the Pikel value as a grey level with a score of 0 to 250. This study complied with the Declaration of Helsinki and was approved by the Ethics Committee of Shahid Beheshti University of Medical Sciences. It was also registered with the Database for Clinical Trials (Iranian Registry of Clinical Trials, reference no: IRCT2016022526769N1). 2.2. Statistical analysis Comparison of the average of quantitative variables between groups was made by a t-test and repeated measurement analysis of variation (ANOVA), and for quality variables, the chi-square test was used. Also, P < 0.05 was considered as statistically significant. Fig. 2. The electromagnetic pulse device.
3. Results questionnaire, sensory changes had been described as numbness, pinching, tingling, painful, burning, and no sensory changes. Also, the maximum amount of mouth opening determined by measuring the distance between upper and lower anterior teeth with a Vernier caliper. Displacement of the fracture region was assessed bimanually after the MMF opening. Malocclusion was diagnosed by evaluating the relationship between the anterior and posterior teeth and noting signs of infection, such as erythema, edema, and infectious drainage from the fracture region. In addition, bone density was determined by computerized quantitative radio densitometry (Fig. 3). Standardized digital panoramic radiographs at days 0, 14, and 28 post-surgery were performed for each patient with a digital panoramic and cephalometric imaging system (Cranex D; Sorodex, Inc., Germany) using the following exposure parameters; 57–85 kVp, ten mA, and exposure of the panoramic program set at 11 s. The digital images were evaluated by Sorodex, Inc.’s Digora for Windows 2.7 (DfW 2.7) software. On panoramic
All 32 patients (24 males, 8 females) enrolled in this study had been diagnosed with a mandibular fracture. The mean age of the study patients was 37.03 10.5 (19–51) years (Table 1). The mean bone density immediately after treatment was 130.6 18.6 gr/cm2 in the case group and 145.6 18.7 gr/cm2 in the control group; at post-surgery week 2, it was 124.10 18.2 gr/ cm2 in the case group and 128.4 18.9 gr/cm2 in the control group; at post-surgery week 4, it was 144.6 19.3 gr/cm2 in the case group and 131 20 gr/cm2 in the control group. Mean of bone density changes at various times in the different study groups is shown in Figs. 4 and 5. The instant mean pain score post-surgery in the case group was 6.7 1.4; at post-surgery day 1, it was 2.8 1.2; at post-surgery week 1, it was 1.75 1.06; and at post-surgery week 2, it was 0.81 0.83. In the control group, it was 7.5 0.75 immediately postsurgery; at post-surgery day 1, it was 5.6 1.01; at post-surgery week 1, it was 3.85 0.9; and at post-surgery week 2, it was
Fig. 3. Bone density is determined by using quantitative radiodensitometry using X-ray.
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Table 1 Comparison of demographic data between two study groups. All
Case group
Control group
P-value
37.06 10.6 13 (81.3%) 3 (18.8%)
37 10.7 11 (68.8%) 5 (31.3%)
0.987
Male Female
37.06 10.5 24 (75%) 8 (25%)
Left angle Right angle Left body Right body Symphysis Right parasymphysis Left parasymphysis Accident Strife Sports injury Falling from height
5 (15.6%) 5 (15.6%) 4 (12.5%) 8 (25%) 2 (6.3%) 3 (9.4%) 5 (15.6%) 22 (68.8%) 5 (15.6%) 3 (9.4%) 2 (6.3%)
3 (18.8%) 3 (18.8%) 3 (18.8%) 3 (18.8%) 1 (6.3%) 2 (12.5%) 1 (6.3%) 10 (62.5%) 2 (12.5%) 2 (12.5%) 2 (12.5%)
2 (12.5%) 2 (12.5%) 1 (6.3%) 5 (31.3%) 1 (6.3%) 1 (6.3%) 4 (25%) 12 (75%) 3 (18.8%) 1 (6.3%) 0 (0%)
Age (year) Sex
Fracture region
Fracture etiology
2.4 0.9. The mean of pain score changes at different times and in the different study groups are shown in Figs. 6 and 7. The maximum amount of mouth opening was 46.7 3.02 mm in the case-control, and 34 5.4 mm in the control group was statistically significant (P = 0.0001). Additionally, the comparison between the number of sensory changes at different times for the two study groups showed no significant difference (Table 2). Furthermore, the malocclusion numbers between the two groups were not significantly different (P > 0.05). None of the patients showed signs of fracture displacement or infection. 4. Discussion Recently, new methods have been used in the healing of mandibular fractures. Therefore, for the prevention of side effects, such as dental and periodontal problems, temporal joint disorder, nutrition failure, and occupational disability, using a method making the fixation course shorter is very important. In this randomized controlled study, we investigated the clinical efficacy of the PEMF in the post-surgery mandibular fracture. We followed up relevant factors, including the amount of bone density, mouth
0.414
0.672
0.438
opening, pain, and malocclusion between the case and control groups. In this study, the use of a long period immobilization with MMF was in accordance with other studies that showed clinical stability of 75–80% of mandibular fractures by week 4 [13]. One study reported that 4.67 0.72 weeks were required for mandibular fracture healing when treated by MMF [14]. In the current study, bone density changes were measured with a CADIA (computer-assisted densitometric image analysis) system. Compared to the conventional method, this is a feasible, low-cost method with the ability to measure quantitative changes of density by consecutive radiographs; clinical studies also showed a significant relationship between CADIA and conventional quantitative measurements for measurement of bone mineralization [15]. According to the CADIA bone density measurement results, values of bone density had decreased at post-surgery day 14 in both groups, which could have been due to start of the regeneration stage. However, at post-surgery day 28, the value of bone density had increased, possibly due to callus regeneration. These findings generally agree with those in a study that reported a decrease in mean bone densities at post-surgery day 15 and an increase in these values at post-surgery day 30 [2]. These results can be explained by the concept of fracture healing that secondary bone healing using either biologic immobilization alone or medical fixation is characterized by callus formation [16]. The bone healing sequence can be summarized as follows: formation of inflammation and hematoma; interfragmentary stabilization by periosteal and endosteal callus generation; restoration of continuity by membranous and endochondral ossification; Haversian remodeling and functional adaption [17].
Fig. 4. Comparison of the mean bone density at different times in the groups.
Another study showed that the largest decrease in optical density was seen at days 7–14, and the largest increase in optical density was at weeks 6–8 after repositioning and fixation of the fracture site [18]. In contrast, one study reported an unanticipated increase in bone density at post-surgery day 15, and a more significant decrease in optical density was seen at day 30 in the MMF group because of callus formation [19]. It has been reported that fracture healing goes through four phases in humans including: hematoma formation; early inflammatory phase (weeks 2–4); repair (proliferation and differentiation within 1–2 months); and the late remodeling phase, which lasts for months or even years [20]. An animal model study reported that fracture healing is
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Fig. 5. Comparison of bone density changes at several times between the two groups.
characterized by three overlapping phases: the initial inflammatory response, callus generation, and initial bony union and bone remodeling. Thus, the inflammatory phase by the end of postsurgery week 4 leads to a decrease in the mean bone density values [2]. Also, in this study, bone density changes showed no significant difference between the two groups using CADIA at post-surgery days 14 and 28. However, in the case group, the bone density value was higher than in the control group at day 28. This result has also been confirmed by other studies. In a related study, healing of a nonunion fractured lateral condyle of the humerus was reported by pulsed electromagnetic induction [21]. Probably, contact of bony cells with the PEMF immediately leads to cross-induced intracellular signals and is related with an anabolic bony cell response [22]. Also, the regenerative effect of the PEMF can be due to an increase the growth factor in several stages [23]. In some studies, effective therapeutic doses of the PEMF were evaluated and showed that an increase of the value of contact with the PEMF leads to an increase in treatment success [24]. In our study, contact duration with radiation immediately post-surgery
Fig. 6. Comparison the mean pain score at different times in the groups.
was 6 h; at post-surgery day 2, it was 3 h daily; and from day 7 onwards, it was 1.5 hours daily for 6 d. There was a significant difference in evaluation of pain changes at days 1, 7, and 14 between the two groups in this study, as at day14, the pain was slight in the case group and moderate in the control group. It seems that systemic emission of the PEMF with its anti-inflammatory, analgesic, and anti-nociceptive effects leads to a reduction in pain, and by binding to anti-CD3 in lymphocyte receptors, it leads to a reduction in inflammatory responses [25]. The regenerative effect of this could be due to a decrease of the inflammation during the regeneration phase, which has been confirmed by some studies. Some studies showed that application of PEMF for 20 min daily for 10 d decreases chronic pains which are resistant to conventional treatments [26]. Most likely, the difference between this study and other studies is due to differences in the strength points and frequency of the PEMF used. In the current study, all broken bones were stabilized, and no symptoms of infection were observed in the patients. Sensory changes showed no significant difference at post-surgery days 30 and 60 for either of the two groups. No malocclusion was reported in any of the case group patients. The only reported malocclusion was in one control group patient. Furthermore, the amount of mouth opening showed a significant difference in the case group. In the natural process of ossification, the PEMF is induced by electrical currents generated during bone mechanical leading, which has led to research about PEMF effects on bone. In vitro studies reported that several types of growth factors affected bone metabolism with bone morphogenetic protein 2 (BMP-2), transforming growth factor beta (TGF-b), and insulin-like growth factor II (IGF-II), playing an important role in bone metabolism [27]. PEMF results can provoke stimulatory effects on bone by the activation of extracellular signal-regulated kinase (ERK), mitogen-activated protein kinase (MAPK), and prostaglandin synthesis [22,28]. Thus, PEMF has been widely used in the healing and regeneration of nonunion fractures [29]. Some clinical studies reported PEMF affects osteogenesis stimulation in patients in the nonunion fractured region, reduces delays in regeneration arthrodesis of the foot and ankle, increases union speed of spinal cord fracture [30], and heals the head of the femur osteonecrosis [31]. The stimulatory effect of the PEMF stimulates an increase in limb length, increase in callus formation, maturation of the distraction region, and more rapid evolution of the external fixation instrument [32]. However, the mechanism of the increase in osteogenesis the PEMF remains unknown.
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Fig. 7. Comparison of the pain changes at several times between the two groups.
Table 2 Comparison of amount of sensory changes at different times in the two groups.
Before surgery 30th postoperative day 60th postoperative day
Sensory
All
Positive Negative Positive Negative Positive Negative
19 13 18 14 16 16
(59.4%) (40.6%) (56.3%) (43.8%) (50%) (50%)
In summary, this project was conducted because of the increasing prevalence of facial fractures, particularly of the mandible, and the importance of faster healing and return of normal jaw function by using an easy, inexpensive, non-invasive method for accelerating bone regeneration. There are conflicting opinions about the healing effect of magnetic fields in bone regeneration, decreasing morbidity after surgery, importance of the preservation of the beauty and function of the face, reducing hospitalization time, reduction of treatment costs, temporomandibular joint disorder due to prolonged intermaxillary fixation, nutrition failure, and dental or periodontal problems following oral health problems; however, the positive effect of magnetic fields on the process of regeneration and healing of long bone fractures has been substantiated by research. Moreover, there are a growing number of studies on the effects of these fields on the mandible, usability of research results, and cost-effectiveness of treatment. 5. Conclusion According to this study, post-surgery PEMF leads to an increase in bone density, faster recovery, an increase in the formation of new bone, further opening of the mouth, and a decrease in pain. The application of PEMF is uncomplicated, noninvasive, and easy to apply. It is an acceptable and effective method for the initiation of healing and increasing regeneration speed of the fracture region. Therefore, using the PEMF as an adjuvant treatment according to this study protocol can be suggested to oral, jaw, and face surgeons for the healing of mandibular fractures. However, further welldesigned studies are needed to more comprehensibly evaluate this treatment. Declaration of interest The authors declare that they have no competing interest.
Case group
Control group
P-value
10 (62.5%) 6 (37.5%) 9 (56.3%) 7 (43.8%) 7 (43.8%) 9 (56.3%)
9 7 9 7 9 7
0.719
(56.3%) (43.8%) (56.3%) (43.8%) (56.3%) (43.8%)
1.0 0.480
Acknowledgments This study was the postgraduate thesis of Dr. Farshad Vossoughi and was supported by Shahid Beheshti University of Medical Sciences (grant no. 689). We would like to express our sincere thanks to colleagues for help in data acquisition. Clinical trial registration number: IRCT2016022526769N1 References [1] Haug RH, Prather J, Indresano AT. An epidemiologic survey of facial fractures and concomitant injuries. Int J Oral Maxillofac Surg 1990;48(9):926–32. [2] Refai H, Radwan D, Hassanien N. Radiodensitometric assessment of the effect of pulsed electromagnetic field stimulation versus low intensity laser irradiation on Mandibular fracture repair: a preliminary clinical trial. Int J Oral Maxillofac Surg 2014;13(4):451–7. [3] Hoffman WY, Barton RM, Price M, Mathes SJ. Rigid internal fixation vs. traditional techniques for the treatment of mandible fractures. J Trauma 1990;30(8):1032–5 [discussion 5-6]. [4] Kromer H. Closed and open reduction of condylar fractures. Dent Rec 1953;73:569. [5] Cawood J. Small plate osteosynthesis of mandibular fractures. Br J Oral Maxillofac Surg 1985;23(2):77–91. [6] Bertone A, Pittman D, Bouxsein M, Li J, Clancy B, Seeherman H. Adenoviralmediated transfer of human BMP-6 gene accelerates healing in a rabbit ulnar osteotomy model. J Orthop Res 2004;22(6):1261–70. [7] Doetsch A, Faber J, Lynnerup N, Wa¨tjen I, Bliddal H, Danneskiold–Samsøe B. The effect of calcium and vitamin D3 supplementation on the healing of the proximal humerus fracture: a randomized placebo-controlled study. Calcif Tissue Int 2004;75(3):183–8. [8] Muhonen A, Haaparanta M, Gro¨nroos T, Bergman J, Knuuti J, Hinkka S, et al. Osteoblastic activity and neoangiogenesis in distracted bone of irradiated rabbit mandible with or without hyperbaric oxygen treatment. Int J Oral Maxillofac Surg 2004;33(2):173–8. [9] Chao E, Inoue N. Biophysical stimulation of bone fracture repair, regeneration and remodelling. Eur Cell Mater 2003;6:72–84. [10] Shi H-F, Cheung W-H, Qin L, AH-C Leung, Leung K-S. Low-magnitude highfrequency vibration treatment augments fracture healing in ovariectomyinduced osteoporotic bone. Bone 2010;46(5):1299–305. [11] Griffin XL, Costa ML, Parsons N, Smith N. Electromagnetic field stimulation for treating delayed union or non-union of long bone fractures in adults. Cochrane Library 2011.
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Original Article
Effect of pulsed electromagnetic field on mandibular fracture healing: A randomized control trial, (RCT) H. Mohajerani a, F. Tabeie b, F. Vossoughi c, E. Jafari d, M. Assadi d,* a
Department of Oral and Maxillofacial Surgery, School of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran, Iran Department of Nuclear Medicine, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran c Department of Oral and Maxillofacial Surgery, School of dentistry, Hormozgan University of Medical Sciences, Bandar Abbas, Iran d The Persian Gulf Nuclear Medicine Research Center, Bushehr University Of Medical Sciences, Bushehr, Iran b
A R T I C L E I N F O
A B S T R A C T
Article history: Received 12 February 2018 Accepted 25 February 2019 Available online 2 March 2019
Introduction: Currently, the pulsed electromagnetic field (PEMF) method is utilized for the treatment of nonunion long bone fractures. Considering the established effect of the PEMF on the acceleration of the bone healing process, we conducted this study to evaluate the effect of PEMF on the healing process in mandibular bone fractures. Material and methods: : This research was a randomized control trial (RCT) study. The sample consisted of patients with a mandibular fracture who were hospitalized in order to receive closed reduction treatment. The participants were randomly selected and then sequentially divided into two groups of 16 participants each (controls = 16, cases = 16). The patients in the control group received conventional therapy without any extra treatment, while the patients in the case group received PEMF therapy in addition to conventional therapy. For the PEMF therapy, patients in the case group received immediate post-surgery PEMF therapy for 6 h. Next, they received 3 h of exposure for the next 6 d, and finally, the same process was repeated for 1.5 h for post-surgery days 8–13. The maxillomandibular fixation (MMF) device was removed at post-surgery week 4. The patients in the control group, however, did not receive any extra treatment. The efficiency of the treatment modalities was evaluated clinically and radiographically. For the radiographical assessment, we employed a direct digital panoramic machine to calculate the computerized density of the bone, and those measurements were used for comparison of the results between the control group and the study patients. Results: There was no significant difference in the mean bone density values between the two groups (P > 0.05). However, the percentage of changes in bone density of the two groups revealed that the case group had insignificant decreases at post-surgery day 14 and a significant increase at post-surgery day 28 compared with the control group (P < 0.05). After releasing the MMF, a bimanual mobility test of the fractured segments showed the stability of the segments in all patients. In the case group, the mouth opening was significantly more stable than that of the control group (P < 0.05). Conclusion: PEMF therapy postoperatively leads to increased bone density, faster recovery, increased formation of new bone, a further opening of the mouth, and decreased pain.
C 2019 Elsevier Masson SAS. All rights reserved.
Keywords: Pulsed electromagnetic fields Bone density Mandibular fracture Bone healing Pain management
1. Introduction The mandible is the most common bone in the jaw that is injured in facial trauma. Although the mandible is the largest and strongest facial bone, fractures are quite common, and in the middle region of the face, they occur two to three times more often than in other parts of the face [1].
* Corresponding author. E-mail address: [email protected] (M. Assadi). https://doi.org/10.1016/j.jormas.2019.02.022 C 2019 Elsevier Masson SAS. All rights reserved. 2468-7855/
The basic treatment principles for mandibular fracture include reduction, fixation, immobilization, and supportive therapies. Reduction can be attained with two procedures, which include the closed and open techniques. In the closed reduction technique, the fracture site is not surgically exposed, and the reduction is obtained with palpation of the bony fragments and restoration of the dental occlusion. Open reduction includes exposure of the fracture region to allow direct observation, validation of the procedure, and direct insertion of a fixation device at the fracture site [2].
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Open reduction was found to be more popular than closed reduction among surgeons. However, the closed technique is still a valuable option when considering treatment of mandibular fracture [3]. In closed reduction, there is no threat of surgical morbidity, hospitalization, and the high cost of open reductions [4]. However, the long period of immobilization required and the subsequent delay of rehabilitation are significant limitations of the closed technique [5]. In pharmacological studies, a range of items, such as the regional use of growth factors, calcium sulfate, bone morphogenetic proteins [6], systemic reception of vitamin D, parathyroid hormone, estrogen, and base phosphonates, were evaluated for increasing the speed of fracture healing [7]. Other treatment procedures, including electrical, mechanical, and magnetic stimulation, the use of shock waves, hyperbaric oxygen treatment, and noninvasive ultrasound, were also evaluated for increasing the speed of fracture healing [8]. In the last decade, among the reported treatment procedures, the use of the biophysical intervention of pulsed electromagnetic field (PEMF) therapy was considered because it is a noninvasive, convenient, and easy to use intervention [9,10]. In 1970, the pulsed magnetic field was developed as a beneficial instrument for fracture regeneration. Although the mechanism of its action was unknown, it caused the effective regeneration of nonunion bone fractures [11]. In theory, PEMF offers a number of advantages, such as reactivation of the biological procedure of bone regeneration, simplification of fracture regeneration, and a shortened duration of treatment. In addition, some studies reported that PEMF has a positive effect on bone regeneration with certain energy transmission settings. These studies were commonly performed on long bones and vertebral bones [12]. However, PEMF is still not fully understood; therefore, one of the aims of this study was evaluation of the effect of the pulsed magnetic field on the regeneration process in patients with mandibular fracture. Also, as mentioned, since the most significant limitation of closed reduction is the need for a long period of immobilization, an additional aim of this study was the evaluation of the effect of PEMF on reducing this period.
2. Material and methods 2.1. Participants and study design This study was a randomized clinical trial project conducted among candidate patients for closed reduction treatment hospitalized with a mandibular fracture in the oral, jaw, and facial surgery
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department of a tertiary university-affiliated hospital in Tehran, Iran. The sampling method was by census. In the studied population, 16 patients were in the control group, and 16 patients underwent PEMF treatment. Inclusion criteria included the patient’s consent to participate in the study, a mandibular fracture in the dental region, the possibility of the application of an arch bar and maxillary mandibular fixation (MMF), absence of signs of infection in the fracture region, lack of systemic diseases affecting favorable stages of bone regeneration, and treatment indications of closed reduction. Exclusion criteria included lack of consent to participate in the study and contraindications of closed reduction treatment. Postoperatively, all of the patients received 1 g cefazolin and 8 mg of dexamethasone intravenously and 5 mg of morphine sulfate intramuscularly. For closed reduction, the region of the mandibular fracture underwent reduction manually, and after closing the arch bar, MMF was established in the patients with 24gauge wire (Fig. 1). Then, using the block randomization method in the form of foursome block and non-blind, all the patients were randomly divided into two groups, which included cases (16 patients) and controls (16 patients). The case group was exposed to PEMF, while the control group was not exposed to any radiation, and the device was turned off for them. The PEMF device was a portable unit that consisted of a coil and a magnetic field generator source along with a power supply source-generated PEMF with 1 millitesla (mT) intensity and 40 Hz frequency. The coil was fixed in the fracture zone (Fig. 2). The protocol for exposure to the PEMF was as follows: immediately post-surgery for 6 h with the intensity of 1 mT and a frequency of 40 Hz; three hours daily for the next 6 d (days 2–7) post-surgery with the intensity of 1 mT and a frequency of 40 Hz; 1.5 hours daily for the next 6 d (days 8–13) after operation with the intensity of 1 mT and a frequency of 40 Hz. MMF was opened in the case group after 4 weeks and in the control group after 6 weeks post-surgery. Patients were followed up on the day of surgery, and 7, 14, and 28 d post-surgery. Patient pain, sensory changes in the fracture region, the maximum amount of mouth opening, displacement of the fracture region, infection, and malocclusion of the fracture region were evaluated at each visit. The Visual Analog Scale (VAS) was used for pain measurement and rated from 1–10. On this scale, 0, 1–3, 4–7, and 8–10 were considered as no pain, slight pain, moderate pain, and severe pain, respectively. Patient verbal affirmation of abnormal lip sensation was used for evaluation of sensory changes along with a questionnaire that had been completed by the patients. In this
Fig. 1. A patient who underwent maxillary mandibular fixation (MMF) (A) and pulsed electromagnetic field (PEMF) therapy.
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images, Dfw 2.7 is capable of measuring the bone density in the fracture site by measurement of the Pikel value as a grey level with a score of 0 to 250. This study complied with the Declaration of Helsinki and was approved by the Ethics Committee of Shahid Beheshti University of Medical Sciences. It was also registered with the Database for Clinical Trials (Iranian Registry of Clinical Trials, reference no: IRCT2016022526769N1). 2.2. Statistical analysis Comparison of the average of quantitative variables between groups was made by a t-test and repeated measurement analysis of variation (ANOVA), and for quality variables, the chi-square test was used. Also, P < 0.05 was considered as statistically significant. Fig. 2. The electromagnetic pulse device.
3. Results questionnaire, sensory changes had been described as numbness, pinching, tingling, painful, burning, and no sensory changes. Also, the maximum amount of mouth opening determined by measuring the distance between upper and lower anterior teeth with a Vernier caliper. Displacement of the fracture region was assessed bimanually after the MMF opening. Malocclusion was diagnosed by evaluating the relationship between the anterior and posterior teeth and noting signs of infection, such as erythema, edema, and infectious drainage from the fracture region. In addition, bone density was determined by computerized quantitative radio densitometry (Fig. 3). Standardized digital panoramic radiographs at days 0, 14, and 28 post-surgery were performed for each patient with a digital panoramic and cephalometric imaging system (Cranex D; Sorodex, Inc., Germany) using the following exposure parameters; 57–85 kVp, ten mA, and exposure of the panoramic program set at 11 s. The digital images were evaluated by Sorodex, Inc.’s Digora for Windows 2.7 (DfW 2.7) software. On panoramic
All 32 patients (24 males, 8 females) enrolled in this study had been diagnosed with a mandibular fracture. The mean age of the study patients was 37.03 10.5 (19–51) years (Table 1). The mean bone density immediately after treatment was 130.6 18.6 gr/cm2 in the case group and 145.6 18.7 gr/cm2 in the control group; at post-surgery week 2, it was 124.10 18.2 gr/ cm2 in the case group and 128.4 18.9 gr/cm2 in the control group; at post-surgery week 4, it was 144.6 19.3 gr/cm2 in the case group and 131 20 gr/cm2 in the control group. Mean of bone density changes at various times in the different study groups is shown in Figs. 4 and 5. The instant mean pain score post-surgery in the case group was 6.7 1.4; at post-surgery day 1, it was 2.8 1.2; at post-surgery week 1, it was 1.75 1.06; and at post-surgery week 2, it was 0.81 0.83. In the control group, it was 7.5 0.75 immediately postsurgery; at post-surgery day 1, it was 5.6 1.01; at post-surgery week 1, it was 3.85 0.9; and at post-surgery week 2, it was
Fig. 3. Bone density is determined by using quantitative radiodensitometry using X-ray.
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Table 1 Comparison of demographic data between two study groups. All
Case group
Control group
P-value
37.06 10.6 13 (81.3%) 3 (18.8%)
37 10.7 11 (68.8%) 5 (31.3%)
0.987
Male Female
37.06 10.5 24 (75%) 8 (25%)
Left angle Right angle Left body Right body Symphysis Right parasymphysis Left parasymphysis Accident Strife Sports injury Falling from height
5 (15.6%) 5 (15.6%) 4 (12.5%) 8 (25%) 2 (6.3%) 3 (9.4%) 5 (15.6%) 22 (68.8%) 5 (15.6%) 3 (9.4%) 2 (6.3%)
3 (18.8%) 3 (18.8%) 3 (18.8%) 3 (18.8%) 1 (6.3%) 2 (12.5%) 1 (6.3%) 10 (62.5%) 2 (12.5%) 2 (12.5%) 2 (12.5%)
2 (12.5%) 2 (12.5%) 1 (6.3%) 5 (31.3%) 1 (6.3%) 1 (6.3%) 4 (25%) 12 (75%) 3 (18.8%) 1 (6.3%) 0 (0%)
Age (year) Sex
Fracture region
Fracture etiology
2.4 0.9. The mean of pain score changes at different times and in the different study groups are shown in Figs. 6 and 7. The maximum amount of mouth opening was 46.7 3.02 mm in the case-control, and 34 5.4 mm in the control group was statistically significant (P = 0.0001). Additionally, the comparison between the number of sensory changes at different times for the two study groups showed no significant difference (Table 2). Furthermore, the malocclusion numbers between the two groups were not significantly different (P > 0.05). None of the patients showed signs of fracture displacement or infection. 4. Discussion Recently, new methods have been used in the healing of mandibular fractures. Therefore, for the prevention of side effects, such as dental and periodontal problems, temporal joint disorder, nutrition failure, and occupational disability, using a method making the fixation course shorter is very important. In this randomized controlled study, we investigated the clinical efficacy of the PEMF in the post-surgery mandibular fracture. We followed up relevant factors, including the amount of bone density, mouth
0.414
0.672
0.438
opening, pain, and malocclusion between the case and control groups. In this study, the use of a long period immobilization with MMF was in accordance with other studies that showed clinical stability of 75–80% of mandibular fractures by week 4 [13]. One study reported that 4.67 0.72 weeks were required for mandibular fracture healing when treated by MMF [14]. In the current study, bone density changes were measured with a CADIA (computer-assisted densitometric image analysis) system. Compared to the conventional method, this is a feasible, low-cost method with the ability to measure quantitative changes of density by consecutive radiographs; clinical studies also showed a significant relationship between CADIA and conventional quantitative measurements for measurement of bone mineralization [15]. According to the CADIA bone density measurement results, values of bone density had decreased at post-surgery day 14 in both groups, which could have been due to start of the regeneration stage. However, at post-surgery day 28, the value of bone density had increased, possibly due to callus regeneration. These findings generally agree with those in a study that reported a decrease in mean bone densities at post-surgery day 15 and an increase in these values at post-surgery day 30 [2]. These results can be explained by the concept of fracture healing that secondary bone healing using either biologic immobilization alone or medical fixation is characterized by callus formation [16]. The bone healing sequence can be summarized as follows: formation of inflammation and hematoma; interfragmentary stabilization by periosteal and endosteal callus generation; restoration of continuity by membranous and endochondral ossification; Haversian remodeling and functional adaption [17].
Fig. 4. Comparison of the mean bone density at different times in the groups.
Another study showed that the largest decrease in optical density was seen at days 7–14, and the largest increase in optical density was at weeks 6–8 after repositioning and fixation of the fracture site [18]. In contrast, one study reported an unanticipated increase in bone density at post-surgery day 15, and a more significant decrease in optical density was seen at day 30 in the MMF group because of callus formation [19]. It has been reported that fracture healing goes through four phases in humans including: hematoma formation; early inflammatory phase (weeks 2–4); repair (proliferation and differentiation within 1–2 months); and the late remodeling phase, which lasts for months or even years [20]. An animal model study reported that fracture healing is
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Fig. 5. Comparison of bone density changes at several times between the two groups.
characterized by three overlapping phases: the initial inflammatory response, callus generation, and initial bony union and bone remodeling. Thus, the inflammatory phase by the end of postsurgery week 4 leads to a decrease in the mean bone density values [2]. Also, in this study, bone density changes showed no significant difference between the two groups using CADIA at post-surgery days 14 and 28. However, in the case group, the bone density value was higher than in the control group at day 28. This result has also been confirmed by other studies. In a related study, healing of a nonunion fractured lateral condyle of the humerus was reported by pulsed electromagnetic induction [21]. Probably, contact of bony cells with the PEMF immediately leads to cross-induced intracellular signals and is related with an anabolic bony cell response [22]. Also, the regenerative effect of the PEMF can be due to an increase the growth factor in several stages [23]. In some studies, effective therapeutic doses of the PEMF were evaluated and showed that an increase of the value of contact with the PEMF leads to an increase in treatment success [24]. In our study, contact duration with radiation immediately post-surgery
Fig. 6. Comparison the mean pain score at different times in the groups.
was 6 h; at post-surgery day 2, it was 3 h daily; and from day 7 onwards, it was 1.5 hours daily for 6 d. There was a significant difference in evaluation of pain changes at days 1, 7, and 14 between the two groups in this study, as at day14, the pain was slight in the case group and moderate in the control group. It seems that systemic emission of the PEMF with its anti-inflammatory, analgesic, and anti-nociceptive effects leads to a reduction in pain, and by binding to anti-CD3 in lymphocyte receptors, it leads to a reduction in inflammatory responses [25]. The regenerative effect of this could be due to a decrease of the inflammation during the regeneration phase, which has been confirmed by some studies. Some studies showed that application of PEMF for 20 min daily for 10 d decreases chronic pains which are resistant to conventional treatments [26]. Most likely, the difference between this study and other studies is due to differences in the strength points and frequency of the PEMF used. In the current study, all broken bones were stabilized, and no symptoms of infection were observed in the patients. Sensory changes showed no significant difference at post-surgery days 30 and 60 for either of the two groups. No malocclusion was reported in any of the case group patients. The only reported malocclusion was in one control group patient. Furthermore, the amount of mouth opening showed a significant difference in the case group. In the natural process of ossification, the PEMF is induced by electrical currents generated during bone mechanical leading, which has led to research about PEMF effects on bone. In vitro studies reported that several types of growth factors affected bone metabolism with bone morphogenetic protein 2 (BMP-2), transforming growth factor beta (TGF-b), and insulin-like growth factor II (IGF-II), playing an important role in bone metabolism [27]. PEMF results can provoke stimulatory effects on bone by the activation of extracellular signal-regulated kinase (ERK), mitogen-activated protein kinase (MAPK), and prostaglandin synthesis [22,28]. Thus, PEMF has been widely used in the healing and regeneration of nonunion fractures [29]. Some clinical studies reported PEMF affects osteogenesis stimulation in patients in the nonunion fractured region, reduces delays in regeneration arthrodesis of the foot and ankle, increases union speed of spinal cord fracture [30], and heals the head of the femur osteonecrosis [31]. The stimulatory effect of the PEMF stimulates an increase in limb length, increase in callus formation, maturation of the distraction region, and more rapid evolution of the external fixation instrument [32]. However, the mechanism of the increase in osteogenesis the PEMF remains unknown.
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Fig. 7. Comparison of the pain changes at several times between the two groups.
Table 2 Comparison of amount of sensory changes at different times in the two groups.
Before surgery 30th postoperative day 60th postoperative day
Sensory
All
Positive Negative Positive Negative Positive Negative
19 13 18 14 16 16
(59.4%) (40.6%) (56.3%) (43.8%) (50%) (50%)
In summary, this project was conducted because of the increasing prevalence of facial fractures, particularly of the mandible, and the importance of faster healing and return of normal jaw function by using an easy, inexpensive, non-invasive method for accelerating bone regeneration. There are conflicting opinions about the healing effect of magnetic fields in bone regeneration, decreasing morbidity after surgery, importance of the preservation of the beauty and function of the face, reducing hospitalization time, reduction of treatment costs, temporomandibular joint disorder due to prolonged intermaxillary fixation, nutrition failure, and dental or periodontal problems following oral health problems; however, the positive effect of magnetic fields on the process of regeneration and healing of long bone fractures has been substantiated by research. Moreover, there are a growing number of studies on the effects of these fields on the mandible, usability of research results, and cost-effectiveness of treatment. 5. Conclusion According to this study, post-surgery PEMF leads to an increase in bone density, faster recovery, an increase in the formation of new bone, further opening of the mouth, and a decrease in pain. The application of PEMF is uncomplicated, noninvasive, and easy to apply. It is an acceptable and effective method for the initiation of healing and increasing regeneration speed of the fracture region. Therefore, using the PEMF as an adjuvant treatment according to this study protocol can be suggested to oral, jaw, and face surgeons for the healing of mandibular fractures. However, further welldesigned studies are needed to more comprehensibly evaluate this treatment. Declaration of interest The authors declare that they have no competing interest.
Case group
Control group
P-value
10 (62.5%) 6 (37.5%) 9 (56.3%) 7 (43.8%) 7 (43.8%) 9 (56.3%)
9 7 9 7 9 7
0.719
(56.3%) (43.8%) (56.3%) (43.8%) (56.3%) (43.8%)
1.0 0.480
Acknowledgments This study was the postgraduate thesis of Dr. Farshad Vossoughi and was supported by Shahid Beheshti University of Medical Sciences (grant no. 689). We would like to express our sincere thanks to colleagues for help in data acquisition. Clinical trial registration number: IRCT2016022526769N1 References [1] Haug RH, Prather J, Indresano AT. An epidemiologic survey of facial fractures and concomitant injuries. Int J Oral Maxillofac Surg 1990;48(9):926–32. [2] Refai H, Radwan D, Hassanien N. Radiodensitometric assessment of the effect of pulsed electromagnetic field stimulation versus low intensity laser irradiation on Mandibular fracture repair: a preliminary clinical trial. Int J Oral Maxillofac Surg 2014;13(4):451–7. [3] Hoffman WY, Barton RM, Price M, Mathes SJ. Rigid internal fixation vs. traditional techniques for the treatment of mandible fractures. J Trauma 1990;30(8):1032–5 [discussion 5-6]. [4] Kromer H. Closed and open reduction of condylar fractures. Dent Rec 1953;73:569. [5] Cawood J. Small plate osteosynthesis of mandibular fractures. Br J Oral Maxillofac Surg 1985;23(2):77–91. [6] Bertone A, Pittman D, Bouxsein M, Li J, Clancy B, Seeherman H. Adenoviralmediated transfer of human BMP-6 gene accelerates healing in a rabbit ulnar osteotomy model. J Orthop Res 2004;22(6):1261–70. [7] Doetsch A, Faber J, Lynnerup N, Wa¨tjen I, Bliddal H, Danneskiold–Samsøe B. The effect of calcium and vitamin D3 supplementation on the healing of the proximal humerus fracture: a randomized placebo-controlled study. Calcif Tissue Int 2004;75(3):183–8. [8] Muhonen A, Haaparanta M, Gro¨nroos T, Bergman J, Knuuti J, Hinkka S, et al. Osteoblastic activity and neoangiogenesis in distracted bone of irradiated rabbit mandible with or without hyperbaric oxygen treatment. Int J Oral Maxillofac Surg 2004;33(2):173–8. [9] Chao E, Inoue N. Biophysical stimulation of bone fracture repair, regeneration and remodelling. Eur Cell Mater 2003;6:72–84. [10] Shi H-F, Cheung W-H, Qin L, AH-C Leung, Leung K-S. Low-magnitude highfrequency vibration treatment augments fracture healing in ovariectomyinduced osteoporotic bone. Bone 2010;46(5):1299–305. [11] Griffin XL, Costa ML, Parsons N, Smith N. Electromagnetic field stimulation for treating delayed union or non-union of long bone fractures in adults. Cochrane Library 2011.
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