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The Effect of Therapeutic Ultrasound on Metallic Implants: A Study in Rats
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ORIGINAL ARTICLE
The Effect of Therapeutic Ultrasound on Metallic Implants: A Study in Rats Barıs¸ Kocaog˘lu, MD, Cengiz Çabukoglu, MD, Nadire Özeras, MD, Mustafa Seyhan, MD, Mustafa Karahan, MD, Selim Yalcin, MD ABSTRACT. Kocaog˘lu B, Çabukoglu C, Özeras N, Seyhan M, Karahan M, Yalcin S. The effect of therapeutic ultrasound on metallic implants: a study in rats. Arch Phys Med Rehabil 20112011;92:1858-62. Objective: To investigate whether therapeutic ultrasound (US) use over metallic implants has the potential for adverse effects as a result of greater temperature increases at the tissuemetal interface. Design: A randomized controlled trial. Setting: A research laboratory. Animals: Sprague-Dawley rats (N⫽40; weight, 230 –300g) were used and divided into 3 study groups. Interventions: In group 1, both limbs of 10 rats were used for evaluation of temperature changes. Metal pins were placed into the femur of the left limb, and the right limbs were used as controls. A thermal sensor was placed into the medulla to record the elevation of tissue temperature during US application. In groups 2 and 3 with 15 rats in each, a midshaft femoral fracture was produced, and intramedullary fixation was performed with metal pins. Group 2 received US treatment for 5 minutes daily and continued for 27 days. Group 3 served as controls. Main Outcome Measures: The rats in groups 2 and 3 were killed on postoperative day 30. The specimens were evaluated by radiology, histopathology, and biomechanics. Results: The presence of metal in bone did not cause an increased temperature rise. US application did not increase or decrease callus formation, and there was no tissue necrosis. The average removal torques of pins in groups did not show a significant difference. Conclusions: Internal fixation with metallic implants may not be a contraindication for therapeutic US treatment. Key Words: Bone Fracture healing, implant failure, metal; Heating; Loosening; Metallic implant; Rehabilitation; Ultrasound. © 2011 by the American Congress of Rehabilitation Medicine
From the Department of Orthopaedics and Traumatology, Acibadem University Faculty of Medicine, Istanbul (Kocaog˘lu); Department of Orthopaedic Surgery, Pendik Sifa Hospital, Istanbul (Cabukoglu); Departments of Physical Therapy and Rehabilitation (Özeras) and Orthopaedic Surgery (Karahan, Yalcin), Marmara University Faculty of Medicine, Istanbul; and Department of Orthopaedics and Traumatology, Acibadem Kadikoy Hospital, Istanbul (Seyhan), Turkey. No commercial party having a direct financial interest in the results of the research supporting this article has or will confer a benefit on the authors or on any organization with which the authors are associated. Correspondence to Barıs¸ Kocaog˘lu, MD, Assistant Professor, Acibadem University Faculty of Medicine, Department of Orthopaedics and Traumatology, Soyak Evreka, 1. Etap, A1:43, 34880, Soganlik, Kartal, Istanbul, Turkey, e-mail: bariskocaoglu@ gmail.com. Reprints are not available from the authors. 0003-9993/11/9211-00001$36.00/0 doi:10.1016/j.apmr.2011.06.002
Arch Phys Med Rehabil Vol 92, November 2011
LTRASOUND IS DEFINED as acoustic vibration with U frequencies above the audible range. Therapeutic ultrasound (US) involves the use of acoustic energy to produce
thermal and nonthermal effects in tissue.1-3 As ultrasonic waves travel through tissue, they lose energy principally by conversion into heat. The US energy in a specific region is dependent on absorption, beam divergence and reflection.3 Most clinical intensities of therapeutic US are in the 0.5- to 2-W/cm2 (spatial-average temporal-average [SATA]) range. Temperatures of up to 46°C in deep tissues (eg, bone and muscle) are easily achieved with US.3 The concern with US use over arthroplasties and other metallic implants is the potential for local heating. It has been assumed that US application over tissues containing metal may cause greater temperature rises at the tissue-metal interface and influence bone healing.3-5 There is a scarcity of literature on the therapeutic application of US over tissues with metallic implants.2 The effect of therapeutic US on metallic implants was first examined by Kristensen and Sommer.2 In their study, the effect of US on the fixation of 3-hole metal plates on the femur and humerus in dogs was investigated. Four weeks postoperatively, the screws were loosened and the required torque was measured. The removal torque of screws exposed to US was found to be lower than that of unexposed screws, but the difference was not statistically significant. Thus they assumed that therapy with US in clinical dosages could be used without influence on the fixation of a rigid plate. Internal fixation of fractures of long bones with rigid metallic implants is frequently used in clinics. Therefore we aimed to evaluate in this experiment whether treatment with US causes a greater temperature rise than expected in tissues containing metal, and whether this increase in temperature has any harmful effect on implant fixation and bone healing. METHODS Animals and Groups Forty Sprague-Dawley rats (weight, 230 –300g) were used in this study. All rats were individually housed and fed standard rat chow ad libitum throughout the experiment. The rats were divided into 3 study groups: 10 rats in group 1 and 15 rats each in groups 2 and 3. Anesthesia was achieved by ketamine hydrochloride (6mg/kg) and 0.1mg of atropine administered intraperitoneally. Cefazolin sodium, 50mg/kg, was administered intramuscularly to each rat for prophylaxis of infection. Animal Experiment Permission Permission to use laboratory animals was given by the Ethical Commission for Animal Experiments (March 2009-
List of Abbreviations SATA US
spatial-average temporal-average ultrasound
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123). Animal care complied with the guidelines of the authors’ institution, the National Institutes of Health, and the law on the care and use of laboratory animals. US Application US was administrated in continuous wave form at a frequency of 1MHz with an apparatus model Enraf Nonius Sonopuls 590.a The radiating surface of the applicator was 0.5cm2. US was applied with a stroking method over the limb with the implant. Lubricant medium (Lomex ultrasound gel)b was used between the skin and the applicator. Treatments lasted for 5 minutes. Animal Model for Temperature Measurement The left hind limbs of 10 rats in group 1 were used as the experimental sides, and the right limbs were used as control sides. After the routine preparation of both thighs for operation, a 1-cm transverse incision was made through the lateral border of both thighs of each rat. Femurs were exposed by separating tensor fascia latae and vastus lateralis muscles. In the bone, 1mm2 holes were opened, and the transducer of the heat probe was inserted into the medulla. After this procedure, a 1.2-mm stainless steel pin was placed into the left femur of each rat with a retrograde nailing method through a 0.5-cm skin incision over the knee joint. The transducer of the heat probe was in contact with the pin in the left limbs (fig 1). After obtaining a basal temperature, the incisions were closed in routine fashion. Immediately after the surgery, US was applied to each rat at both thighs with a dose of 1W/cm2 (SATA) for 5 minutes. Temperature changes were recorded simultaneously by a heat probe. After temperature measurements, heat probes were removed from all rats. Animal Model for Radiologic, Histologic, and Biomechanical Evaluation The remaining 30 rats were used for these measurements. After routine preparation of the left thigh for operation, a 3-cm transverse incision was made through the lateral border of the thigh. The tensor fascia latae and vastus lateralis muscles were dissected, and the femur was exposed. An experimental fracture was produced in the middle third of the femur with an
Fig 2. An intramedullary nail was used for fracture fixation in groups 2 and 3. The 1.2-mm nail was placed into the medulla through a skin incision over the knee.
electrical saw. An intramedullary nail was used for fracture fixation. Retrograde nailing was performed with a 1.2-mm nail through a skin incision over the knee joint (fig 2). Bleeding was controlled by bipolar electrocautery, the surgical field was irrigated with saline, and the incision was closed with 4-0 silk sutures. No splints were used throughout the experiment, and the rats were allowed to move freely in their cages and kept in an alternating 12-hour day and night cycle. The sutures were removed on the fifth day. All rats in group 2 received US treatment that began on the third day after surgery with a dose of 1W/cm2 (SATA) for 5 minutes daily, for 27 consecutive days. The rats in group 3 did not receive any US treatments and served as controls. All rats in group 2 and 3 were killed on day 30 after surgery with a concentrated solution of pentobarbital (60mg/kg). The specimens were evaluated by radiology, histology, and biomechanics. Radiologic Evaluation Roentgenograms were taken on day 30 after the operation before the rats were killed. The radiographs were evaluated by the same radiologist for callus formation and scored as follows; grade 1, no callus formation; grade 2, mature callus approximating the fracture ends; and grade 3, complete union of the bone.6 All radiologic observations were made by the same pathologist who was blinded to the study groups.
Fig 1. US was applied with to each rat in group 1 at the thigh with a dose of 1W/cm2 (SATA) for 5 minutes. Temperature changes were recorded simultaneously by a heat probe that was placed into the bone medulla.
Histopathology After the rats were killed, the fracture area of each femur was excised en bloc and immersed in 10% formalin solution for fixation and in hydrochloric acid for decalcification at room temperature for 24 hours. The specimens were dehydrated and embedded in paraffin after decalcification was complete. Ten transversal sections of 0.1cm were made through the fracture site. The sections were stained with hematoxylin and eosin.6 All sections were examined by a light microscope (Olympus BX-50)c and evaluated in terms of necrosis. All histologic Arch Phys Med Rehabil Vol 92, November 2011
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observations were made by the same pathologist who was blinded to the study groups. Biomechanics After the rats were killed, the pins were removed from the specimens. The torque required to separate the pin from bone was determined using a system detecting change of torque over time. The Instron deviced was used for this purpose, and the data were recorded for each rat. The signal was transmitted to a curve registration on a servograph and expressed in kg · cm. Statistical Analysis Mean temperature changes in group 1 rats during US application with and without the metallic implant in place were compared using the analysis of variance test. Comparison of radiologic callus formation between groups 2 and 3 was analyzed by the Fisher exact test. Histologic evaluation scores between groups 2 and 3 were compared using the chi-square test. We used the Mann-Whitney U test for comparison of biomechanical test results. A P value of less than .05 was considered significant for all statistical tests.
Fig 3. Rats in group 2 showed good callus formation with different grades. Implant loosening was not observed in any of the rats.
RESULTS Postoperative Complications The general condition of all rats was good. There were no cases of paralysis or infection. Subcutaneous hematoma occurred on the first postoperative day in 6 rats; 4 of the rats were in group 2, and the other 2 were in group 3. Temperature Changes The temperature changes recorded simultaneously during US application by a thermal sensora in the rats in group 1 are shown in table 1. US increased the basal temperature in both limbs significantly (P⫽.02). Conversely, implant placement did not have any effect on temperature changes during therapeutic US application (P⫽.83). Radiology Callus formation was evaluated radiologically in 3 grades on day 30 after the operation (fig 3). Both groups showed overall
good callus formation with 5 of 15 and 8 of 15 animals scoring 2, and 8 of 15 and 6 of 15 animals scoring 3, in groups 2 (US) and 3 (control), respectively. The scorings of callus formation in both groups are shown in table 2. There were no statistically significant differences between the treated group and controls in terms of callus formation (P⫽.76). Histopathology Necrosis was not seen in any of the histopathologic sections in both groups 2 and 3. Callus formation was present in all the sections in the 2 groups. There was no significant difference between the 2 groups in terms of necrosis in both bone and soft tissue sections (P⫽.87). Biomechanics Biomechanical strength of the implant-bone complex is shown in table 3. The strength in the treated group and the
Table 2: Radiologic Evaluation in Groups 2 and 3 Table 1: Temperature Changes Recorded During US Applications in Group 1
Rats
1 2 3 4 5 6 7 8 9 10 Average Mean temperature change
Basal Body Temperature Without US (°C)
38 38 38 38 38 37 38 38 38 38 38†
Left Limb Temperature (US Application With Implant) (°C)
43 42 41 44 42 43 42 42 42 42 42 4.3*
*P⫽.83. P⫽.02.
†
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Right Limb Temperature (US Application Without Implant) (°C)
42 44 43 42 41 41 42 41 43 42 42 4.4*
Rats
Implant Loosening in Group 2 (US Applied)
Callus Formation in Group 2 (US Applied)/ Grades*
Implant Loosening in Group 3
Callus Formation in Group 3/ Grades*
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
No No No No No No No No No No No No No No No
2 3 2 3 3 3 3 1 2 2 2 1 3 3 3
No No No No No No No No No No No No No No No
3 3 2 3 2 2 2 3 2 1 2 3 3 2 2
*There were no statistically significant differences between the treated group controls in terms of callus formation (P⫽.76).
THERAPEUTIC ULTRASOUND AND METALLIC IMPLANTS, Kocaog˘lu Table 3: Biomechanical Strength of the Implant-Bone Complex in Groups 2 and 3 No. of Rats
Group 2 (kg.cm)
Group 3 (kg.cm)
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Mean torque ⫾ SD
2.22 1.45 2.48 2.31 3.66 2.43 2.56 3.78 1.78 3.23 2.45 2.98 1.23 0.98 1.56 2.34⫾0.84*
1.14 4.35 0.98 6.47 1.29 5.9 3.98 3.67 3.56 2.24 2.56 2.45 2.12 0.89 1.46 2.87⫾1.75*
*P⫽.29.
controls was compared by the Mann-Whitney U test. The average removal torques of the 1.2-mm stainless steel pins exposed to US tended to be lower than those of unexposed pins, but the differences were not statistically significant (P⫽.29). DISCUSSION Therapeutic US involves the use of high-frequency acoustic energy to produce thermal and nonthermal effects in tissue. Thermal effects are produced when acoustic energy is absorbed, producing molecular vibration, which results in heat production.1-3 More than 35 clinical uses of US have been described. In the literature, many articles can be found addressing the effectiveness of US in a variety of musculoskeletal conditions including periarticular inflammatory conditions, osteoarthritis, and fracture healing.4 Avoiding US near pacemakers is reasonable because of the potential thermal or mechanical injury to the pacemaker. US over laminectomy sites could theoretically result in spinal cord heating.4-6 The concern with the use of US over arthroplasties and other metallic implants is the potential for excessive local heating. For this reason, metallic implants are generally regarded as contraindications to application of therapeutic US. Theoretically, application of deep heat to metallic implants may cause thermal injury in deep tissue and bone necrosis at the bone-implant interface, and may lead to implant loosening.2,4,7,8 Gersten5 reported that the temperature increases near metal were actually lower than the temperature increases near bone, so metal per se should not be a contraindication to US. But Lehman et al9 cautioned against the use of US near metallic implants and mentioned that the most prudent course would be to avoid US over these areas whenever possible. They assumed that US raises tissue temperature, and metal implants could augment this effect.9 In light of this literature, we used a reproducible animal model to evaluate the effect of therapeutic US on metallic implants. In group 1, a model was created to record the temperature changes in bone medulla during US treatment with and without a metal implant in place. The heat probe was placed into the medulla through a bone window, to enable contact with the rod and minimize heat loss to the environment.
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All rats received US treatment with the same stroking technique using a dose of 1W/cm2 for 5 minutes. The stroking technique is a common technique of US application that allows energy to be distributed more evenly over the treatment site. The basal temperature of the rat was measured as 38°C, and a maximum of 44°C was recorded after US application (mean increase, 4.3°C). This result did not change significantly when the metal was inserted into the femur (4.4°C). In order to show the effects of this temperature increase in tissues containing metal, all rats in group 2 received US that began on day 3 after surgery and continued for 27 days. The rats in group 3 did not receive US, to be able to differentiate the radiologic, histologic, and biomechanical differences in tissues. Four weeks after the operation, implant loosening was not observed in any of the rats in both the treated and the nontreated groups. Both showed good callus formation with different radiologic grades. There were no differences between the groups in terms of callus formation. Histopathologic evaluation revealed no significant differences between the 2 groups in terms of necrosis in both bone and soft tissues. This led us to conclude that the heating effect of US did not harm the tissue containing the metal implant. The average removal torques of the 1.2-mm stainless steel pins exposed to US tended to be lower than those of unexposed rods, but the differences were not statistically significant. Furthermore, no untoward effect of US was seen at the forces used for loosening the pins. We believe that the effect of US was related to its intensity. The dosages used in this study were chosen within the limits of the human therapeutic range, and the threshold for damage was not reached. Study Limitations A limitation of this study is the use of an animal model, as the results cannot always be directly applied to the human patient. A second limitation is that we were not able to get temperature data from soft tissue, bone, and metal. Because they were so close to each other, it was impractical to attempt to separate them. We only obtained data from the medullary space as a separate compartment. Third, the dosages used in this study were chosen within the limits of the human therapeutic range, but they could be high for a rat model. CONCLUSIONS The temperature measurements in the first group of rats showed that the presence of metal in bone did not cause an increased temperature rise in tissues when US was applied. Moreover, US application was not harmful to the tissues containing metal as shown by the results in groups 2 and 3 in light of the radiologic and biomechanical findings. US application to tissues containing metallic implants did not have a negative effect on callus formation, and it did not generate metal implant loosening. We therefore conclude that internal fixation with metallic implants may not be a contraindication for therapeutic ultrasonic treatment. References 1. Dunn F, Frizzel LA. Bioeffect of ultrasound. Therapeutic heat and cold. In: Lehmann J, editor. Rehabilitation medicine. Baltimore: Williams & Wilkins; 1990. p 386. 2. Kristensen ES, Sommer J. Ultrasound influence on internal fixation with a rigid plate in dogs. Arch Phys Med Rehabil 1982;63:371-3. 3. Kottke FJ, Lehman JF, editors. Krusen’s handbook of physical medicine and rehabilitation. 4th ed. Philadelphia: WB Saunders; 1990. Arch Phys Med Rehabil Vol 92, November 2011
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4. Lehmann JF, Brunner GD, McMillan JA. Influence of surgical metal implants on temperature distribution in thigh specimens exposed to ultrasound. Arch Phys Med Rehabil 1958;39:692-5. 5. Gersten JW. Effect of metallic objects on temperature rises produced in tissue by ultrasound. Am J Phys Med Rehabil 1958;37:75-82. 6. Zorlu U, Tercan M, Ozyazgan I, et al. Comparative study of the effect of ultrasound and electro stimulation on bone healing in rats. Am J Phys Med Rehabil 1998:15;427-32. 7. Hadjiargyrou M, Mcleod K, Ryaby J, Rubin C. Enhancement of fracture healing by low intensity ultrasound. Clin Orthop 1998;355:216-29. 8. Huang MH, Yang RC, Ding HJ, Chai CY. Ultrasound effect on level of stress proteins and arthritic histology in experimental arthritis. Arch Phys Med Rehabil 1999:80;551-6.
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9. Lehman JF, Brunner GD, McMillan JA. Ultrasonic effects as demonstrated in live pigs with surgical metallic implants. Arch Phys Med Rehabil 1959;40:483-8. Suppliers a. Enraf Nonius B.V., Vareseweg 127, P.O. Box 12080, NL-3004 GB Rotterdam, The Netherlands. b. Norm Kimya Chemistry, Haramidere San. Sit. B Blk No: 208, Beylikdüzü, Istanbul, Turkey. c. Olympus America, Inc, 3500 Corporate Pkwy, Center Valley, PA 18034. d. ITW Test Ltd, Mahir Iz St, No:1/28, 34662 Altunizade-Uskudar, Istanbul, Turkey.
ORIGINAL ARTICLE
The Effect of Therapeutic Ultrasound on Metallic Implants: A Study in Rats Barıs¸ Kocaog˘lu, MD, Cengiz Çabukoglu, MD, Nadire Özeras, MD, Mustafa Seyhan, MD, Mustafa Karahan, MD, Selim Yalcin, MD ABSTRACT. Kocaog˘lu B, Çabukoglu C, Özeras N, Seyhan M, Karahan M, Yalcin S. The effect of therapeutic ultrasound on metallic implants: a study in rats. Arch Phys Med Rehabil 20112011;92:1858-62. Objective: To investigate whether therapeutic ultrasound (US) use over metallic implants has the potential for adverse effects as a result of greater temperature increases at the tissuemetal interface. Design: A randomized controlled trial. Setting: A research laboratory. Animals: Sprague-Dawley rats (N⫽40; weight, 230 –300g) were used and divided into 3 study groups. Interventions: In group 1, both limbs of 10 rats were used for evaluation of temperature changes. Metal pins were placed into the femur of the left limb, and the right limbs were used as controls. A thermal sensor was placed into the medulla to record the elevation of tissue temperature during US application. In groups 2 and 3 with 15 rats in each, a midshaft femoral fracture was produced, and intramedullary fixation was performed with metal pins. Group 2 received US treatment for 5 minutes daily and continued for 27 days. Group 3 served as controls. Main Outcome Measures: The rats in groups 2 and 3 were killed on postoperative day 30. The specimens were evaluated by radiology, histopathology, and biomechanics. Results: The presence of metal in bone did not cause an increased temperature rise. US application did not increase or decrease callus formation, and there was no tissue necrosis. The average removal torques of pins in groups did not show a significant difference. Conclusions: Internal fixation with metallic implants may not be a contraindication for therapeutic US treatment. Key Words: Bone Fracture healing, implant failure, metal; Heating; Loosening; Metallic implant; Rehabilitation; Ultrasound. © 2011 by the American Congress of Rehabilitation Medicine
From the Department of Orthopaedics and Traumatology, Acibadem University Faculty of Medicine, Istanbul (Kocaog˘lu); Department of Orthopaedic Surgery, Pendik Sifa Hospital, Istanbul (Cabukoglu); Departments of Physical Therapy and Rehabilitation (Özeras) and Orthopaedic Surgery (Karahan, Yalcin), Marmara University Faculty of Medicine, Istanbul; and Department of Orthopaedics and Traumatology, Acibadem Kadikoy Hospital, Istanbul (Seyhan), Turkey. No commercial party having a direct financial interest in the results of the research supporting this article has or will confer a benefit on the authors or on any organization with which the authors are associated. Correspondence to Barıs¸ Kocaog˘lu, MD, Assistant Professor, Acibadem University Faculty of Medicine, Department of Orthopaedics and Traumatology, Soyak Evreka, 1. Etap, A1:43, 34880, Soganlik, Kartal, Istanbul, Turkey, e-mail: bariskocaoglu@ gmail.com. Reprints are not available from the authors. 0003-9993/11/9211-00001$36.00/0 doi:10.1016/j.apmr.2011.06.002
Arch Phys Med Rehabil Vol 92, November 2011
LTRASOUND IS DEFINED as acoustic vibration with U frequencies above the audible range. Therapeutic ultrasound (US) involves the use of acoustic energy to produce
thermal and nonthermal effects in tissue.1-3 As ultrasonic waves travel through tissue, they lose energy principally by conversion into heat. The US energy in a specific region is dependent on absorption, beam divergence and reflection.3 Most clinical intensities of therapeutic US are in the 0.5- to 2-W/cm2 (spatial-average temporal-average [SATA]) range. Temperatures of up to 46°C in deep tissues (eg, bone and muscle) are easily achieved with US.3 The concern with US use over arthroplasties and other metallic implants is the potential for local heating. It has been assumed that US application over tissues containing metal may cause greater temperature rises at the tissue-metal interface and influence bone healing.3-5 There is a scarcity of literature on the therapeutic application of US over tissues with metallic implants.2 The effect of therapeutic US on metallic implants was first examined by Kristensen and Sommer.2 In their study, the effect of US on the fixation of 3-hole metal plates on the femur and humerus in dogs was investigated. Four weeks postoperatively, the screws were loosened and the required torque was measured. The removal torque of screws exposed to US was found to be lower than that of unexposed screws, but the difference was not statistically significant. Thus they assumed that therapy with US in clinical dosages could be used without influence on the fixation of a rigid plate. Internal fixation of fractures of long bones with rigid metallic implants is frequently used in clinics. Therefore we aimed to evaluate in this experiment whether treatment with US causes a greater temperature rise than expected in tissues containing metal, and whether this increase in temperature has any harmful effect on implant fixation and bone healing. METHODS Animals and Groups Forty Sprague-Dawley rats (weight, 230 –300g) were used in this study. All rats were individually housed and fed standard rat chow ad libitum throughout the experiment. The rats were divided into 3 study groups: 10 rats in group 1 and 15 rats each in groups 2 and 3. Anesthesia was achieved by ketamine hydrochloride (6mg/kg) and 0.1mg of atropine administered intraperitoneally. Cefazolin sodium, 50mg/kg, was administered intramuscularly to each rat for prophylaxis of infection. Animal Experiment Permission Permission to use laboratory animals was given by the Ethical Commission for Animal Experiments (March 2009-
List of Abbreviations SATA US
spatial-average temporal-average ultrasound
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123). Animal care complied with the guidelines of the authors’ institution, the National Institutes of Health, and the law on the care and use of laboratory animals. US Application US was administrated in continuous wave form at a frequency of 1MHz with an apparatus model Enraf Nonius Sonopuls 590.a The radiating surface of the applicator was 0.5cm2. US was applied with a stroking method over the limb with the implant. Lubricant medium (Lomex ultrasound gel)b was used between the skin and the applicator. Treatments lasted for 5 minutes. Animal Model for Temperature Measurement The left hind limbs of 10 rats in group 1 were used as the experimental sides, and the right limbs were used as control sides. After the routine preparation of both thighs for operation, a 1-cm transverse incision was made through the lateral border of both thighs of each rat. Femurs were exposed by separating tensor fascia latae and vastus lateralis muscles. In the bone, 1mm2 holes were opened, and the transducer of the heat probe was inserted into the medulla. After this procedure, a 1.2-mm stainless steel pin was placed into the left femur of each rat with a retrograde nailing method through a 0.5-cm skin incision over the knee joint. The transducer of the heat probe was in contact with the pin in the left limbs (fig 1). After obtaining a basal temperature, the incisions were closed in routine fashion. Immediately after the surgery, US was applied to each rat at both thighs with a dose of 1W/cm2 (SATA) for 5 minutes. Temperature changes were recorded simultaneously by a heat probe. After temperature measurements, heat probes were removed from all rats. Animal Model for Radiologic, Histologic, and Biomechanical Evaluation The remaining 30 rats were used for these measurements. After routine preparation of the left thigh for operation, a 3-cm transverse incision was made through the lateral border of the thigh. The tensor fascia latae and vastus lateralis muscles were dissected, and the femur was exposed. An experimental fracture was produced in the middle third of the femur with an
Fig 2. An intramedullary nail was used for fracture fixation in groups 2 and 3. The 1.2-mm nail was placed into the medulla through a skin incision over the knee.
electrical saw. An intramedullary nail was used for fracture fixation. Retrograde nailing was performed with a 1.2-mm nail through a skin incision over the knee joint (fig 2). Bleeding was controlled by bipolar electrocautery, the surgical field was irrigated with saline, and the incision was closed with 4-0 silk sutures. No splints were used throughout the experiment, and the rats were allowed to move freely in their cages and kept in an alternating 12-hour day and night cycle. The sutures were removed on the fifth day. All rats in group 2 received US treatment that began on the third day after surgery with a dose of 1W/cm2 (SATA) for 5 minutes daily, for 27 consecutive days. The rats in group 3 did not receive any US treatments and served as controls. All rats in group 2 and 3 were killed on day 30 after surgery with a concentrated solution of pentobarbital (60mg/kg). The specimens were evaluated by radiology, histology, and biomechanics. Radiologic Evaluation Roentgenograms were taken on day 30 after the operation before the rats were killed. The radiographs were evaluated by the same radiologist for callus formation and scored as follows; grade 1, no callus formation; grade 2, mature callus approximating the fracture ends; and grade 3, complete union of the bone.6 All radiologic observations were made by the same pathologist who was blinded to the study groups.
Fig 1. US was applied with to each rat in group 1 at the thigh with a dose of 1W/cm2 (SATA) for 5 minutes. Temperature changes were recorded simultaneously by a heat probe that was placed into the bone medulla.
Histopathology After the rats were killed, the fracture area of each femur was excised en bloc and immersed in 10% formalin solution for fixation and in hydrochloric acid for decalcification at room temperature for 24 hours. The specimens were dehydrated and embedded in paraffin after decalcification was complete. Ten transversal sections of 0.1cm were made through the fracture site. The sections were stained with hematoxylin and eosin.6 All sections were examined by a light microscope (Olympus BX-50)c and evaluated in terms of necrosis. All histologic Arch Phys Med Rehabil Vol 92, November 2011
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observations were made by the same pathologist who was blinded to the study groups. Biomechanics After the rats were killed, the pins were removed from the specimens. The torque required to separate the pin from bone was determined using a system detecting change of torque over time. The Instron deviced was used for this purpose, and the data were recorded for each rat. The signal was transmitted to a curve registration on a servograph and expressed in kg · cm. Statistical Analysis Mean temperature changes in group 1 rats during US application with and without the metallic implant in place were compared using the analysis of variance test. Comparison of radiologic callus formation between groups 2 and 3 was analyzed by the Fisher exact test. Histologic evaluation scores between groups 2 and 3 were compared using the chi-square test. We used the Mann-Whitney U test for comparison of biomechanical test results. A P value of less than .05 was considered significant for all statistical tests.
Fig 3. Rats in group 2 showed good callus formation with different grades. Implant loosening was not observed in any of the rats.
RESULTS Postoperative Complications The general condition of all rats was good. There were no cases of paralysis or infection. Subcutaneous hematoma occurred on the first postoperative day in 6 rats; 4 of the rats were in group 2, and the other 2 were in group 3. Temperature Changes The temperature changes recorded simultaneously during US application by a thermal sensora in the rats in group 1 are shown in table 1. US increased the basal temperature in both limbs significantly (P⫽.02). Conversely, implant placement did not have any effect on temperature changes during therapeutic US application (P⫽.83). Radiology Callus formation was evaluated radiologically in 3 grades on day 30 after the operation (fig 3). Both groups showed overall
good callus formation with 5 of 15 and 8 of 15 animals scoring 2, and 8 of 15 and 6 of 15 animals scoring 3, in groups 2 (US) and 3 (control), respectively. The scorings of callus formation in both groups are shown in table 2. There were no statistically significant differences between the treated group and controls in terms of callus formation (P⫽.76). Histopathology Necrosis was not seen in any of the histopathologic sections in both groups 2 and 3. Callus formation was present in all the sections in the 2 groups. There was no significant difference between the 2 groups in terms of necrosis in both bone and soft tissue sections (P⫽.87). Biomechanics Biomechanical strength of the implant-bone complex is shown in table 3. The strength in the treated group and the
Table 2: Radiologic Evaluation in Groups 2 and 3 Table 1: Temperature Changes Recorded During US Applications in Group 1
Rats
1 2 3 4 5 6 7 8 9 10 Average Mean temperature change
Basal Body Temperature Without US (°C)
38 38 38 38 38 37 38 38 38 38 38†
Left Limb Temperature (US Application With Implant) (°C)
43 42 41 44 42 43 42 42 42 42 42 4.3*
*P⫽.83. P⫽.02.
†
Arch Phys Med Rehabil Vol 92, November 2011
Right Limb Temperature (US Application Without Implant) (°C)
42 44 43 42 41 41 42 41 43 42 42 4.4*
Rats
Implant Loosening in Group 2 (US Applied)
Callus Formation in Group 2 (US Applied)/ Grades*
Implant Loosening in Group 3
Callus Formation in Group 3/ Grades*
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
No No No No No No No No No No No No No No No
2 3 2 3 3 3 3 1 2 2 2 1 3 3 3
No No No No No No No No No No No No No No No
3 3 2 3 2 2 2 3 2 1 2 3 3 2 2
*There were no statistically significant differences between the treated group controls in terms of callus formation (P⫽.76).
THERAPEUTIC ULTRASOUND AND METALLIC IMPLANTS, Kocaog˘lu Table 3: Biomechanical Strength of the Implant-Bone Complex in Groups 2 and 3 No. of Rats
Group 2 (kg.cm)
Group 3 (kg.cm)
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Mean torque ⫾ SD
2.22 1.45 2.48 2.31 3.66 2.43 2.56 3.78 1.78 3.23 2.45 2.98 1.23 0.98 1.56 2.34⫾0.84*
1.14 4.35 0.98 6.47 1.29 5.9 3.98 3.67 3.56 2.24 2.56 2.45 2.12 0.89 1.46 2.87⫾1.75*
*P⫽.29.
controls was compared by the Mann-Whitney U test. The average removal torques of the 1.2-mm stainless steel pins exposed to US tended to be lower than those of unexposed pins, but the differences were not statistically significant (P⫽.29). DISCUSSION Therapeutic US involves the use of high-frequency acoustic energy to produce thermal and nonthermal effects in tissue. Thermal effects are produced when acoustic energy is absorbed, producing molecular vibration, which results in heat production.1-3 More than 35 clinical uses of US have been described. In the literature, many articles can be found addressing the effectiveness of US in a variety of musculoskeletal conditions including periarticular inflammatory conditions, osteoarthritis, and fracture healing.4 Avoiding US near pacemakers is reasonable because of the potential thermal or mechanical injury to the pacemaker. US over laminectomy sites could theoretically result in spinal cord heating.4-6 The concern with the use of US over arthroplasties and other metallic implants is the potential for excessive local heating. For this reason, metallic implants are generally regarded as contraindications to application of therapeutic US. Theoretically, application of deep heat to metallic implants may cause thermal injury in deep tissue and bone necrosis at the bone-implant interface, and may lead to implant loosening.2,4,7,8 Gersten5 reported that the temperature increases near metal were actually lower than the temperature increases near bone, so metal per se should not be a contraindication to US. But Lehman et al9 cautioned against the use of US near metallic implants and mentioned that the most prudent course would be to avoid US over these areas whenever possible. They assumed that US raises tissue temperature, and metal implants could augment this effect.9 In light of this literature, we used a reproducible animal model to evaluate the effect of therapeutic US on metallic implants. In group 1, a model was created to record the temperature changes in bone medulla during US treatment with and without a metal implant in place. The heat probe was placed into the medulla through a bone window, to enable contact with the rod and minimize heat loss to the environment.
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All rats received US treatment with the same stroking technique using a dose of 1W/cm2 for 5 minutes. The stroking technique is a common technique of US application that allows energy to be distributed more evenly over the treatment site. The basal temperature of the rat was measured as 38°C, and a maximum of 44°C was recorded after US application (mean increase, 4.3°C). This result did not change significantly when the metal was inserted into the femur (4.4°C). In order to show the effects of this temperature increase in tissues containing metal, all rats in group 2 received US that began on day 3 after surgery and continued for 27 days. The rats in group 3 did not receive US, to be able to differentiate the radiologic, histologic, and biomechanical differences in tissues. Four weeks after the operation, implant loosening was not observed in any of the rats in both the treated and the nontreated groups. Both showed good callus formation with different radiologic grades. There were no differences between the groups in terms of callus formation. Histopathologic evaluation revealed no significant differences between the 2 groups in terms of necrosis in both bone and soft tissues. This led us to conclude that the heating effect of US did not harm the tissue containing the metal implant. The average removal torques of the 1.2-mm stainless steel pins exposed to US tended to be lower than those of unexposed rods, but the differences were not statistically significant. Furthermore, no untoward effect of US was seen at the forces used for loosening the pins. We believe that the effect of US was related to its intensity. The dosages used in this study were chosen within the limits of the human therapeutic range, and the threshold for damage was not reached. Study Limitations A limitation of this study is the use of an animal model, as the results cannot always be directly applied to the human patient. A second limitation is that we were not able to get temperature data from soft tissue, bone, and metal. Because they were so close to each other, it was impractical to attempt to separate them. We only obtained data from the medullary space as a separate compartment. Third, the dosages used in this study were chosen within the limits of the human therapeutic range, but they could be high for a rat model. CONCLUSIONS The temperature measurements in the first group of rats showed that the presence of metal in bone did not cause an increased temperature rise in tissues when US was applied. Moreover, US application was not harmful to the tissues containing metal as shown by the results in groups 2 and 3 in light of the radiologic and biomechanical findings. US application to tissues containing metallic implants did not have a negative effect on callus formation, and it did not generate metal implant loosening. We therefore conclude that internal fixation with metallic implants may not be a contraindication for therapeutic ultrasonic treatment. References 1. Dunn F, Frizzel LA. Bioeffect of ultrasound. Therapeutic heat and cold. In: Lehmann J, editor. Rehabilitation medicine. Baltimore: Williams & Wilkins; 1990. p 386. 2. Kristensen ES, Sommer J. Ultrasound influence on internal fixation with a rigid plate in dogs. Arch Phys Med Rehabil 1982;63:371-3. 3. Kottke FJ, Lehman JF, editors. Krusen’s handbook of physical medicine and rehabilitation. 4th ed. Philadelphia: WB Saunders; 1990. Arch Phys Med Rehabil Vol 92, November 2011
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4. Lehmann JF, Brunner GD, McMillan JA. Influence of surgical metal implants on temperature distribution in thigh specimens exposed to ultrasound. Arch Phys Med Rehabil 1958;39:692-5. 5. Gersten JW. Effect of metallic objects on temperature rises produced in tissue by ultrasound. Am J Phys Med Rehabil 1958;37:75-82. 6. Zorlu U, Tercan M, Ozyazgan I, et al. Comparative study of the effect of ultrasound and electro stimulation on bone healing in rats. Am J Phys Med Rehabil 1998:15;427-32. 7. Hadjiargyrou M, Mcleod K, Ryaby J, Rubin C. Enhancement of fracture healing by low intensity ultrasound. Clin Orthop 1998;355:216-29. 8. Huang MH, Yang RC, Ding HJ, Chai CY. Ultrasound effect on level of stress proteins and arthritic histology in experimental arthritis. Arch Phys Med Rehabil 1999:80;551-6.
Arch Phys Med Rehabil Vol 92, November 2011
9. Lehman JF, Brunner GD, McMillan JA. Ultrasonic effects as demonstrated in live pigs with surgical metallic implants. Arch Phys Med Rehabil 1959;40:483-8. Suppliers a. Enraf Nonius B.V., Vareseweg 127, P.O. Box 12080, NL-3004 GB Rotterdam, The Netherlands. b. Norm Kimya Chemistry, Haramidere San. Sit. B Blk No: 208, Beylikdüzü, Istanbul, Turkey. c. Olympus America, Inc, 3500 Corporate Pkwy, Center Valley, PA 18034. d. ITW Test Ltd, Mahir Iz St, No:1/28, 34662 Altunizade-Uskudar, Istanbul, Turkey.