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Biological Aspects and Clinical Importance of Ultrasound Therapy in Bone Healing
Özgür Erdogan, DDS, PhD, Emin Esen, DDS, PhD
Objectives. The purpose of this study was to review past and recent literature findings regarding the effects of ultrasound therapy on bone healing and its clinical efficacy in medical and dental interventions. Methods. A literature review was conducted on the effects of ultrasound therapy on bone healing. The studies regarding clinical applications in long bones and maxillofacial bones were evaluated separately from each other. Results. The effects of therapeutic ultrasound on bone healing have been studied for half a century. Numerous clinical and experimental studies have addressed this relationship, and many of them have shown positive correlations. Although several theories have been proposed to explain the mechanism of action, the exact mechanism has not been fully understood. Conclusions. Therapeutic ultrasound therapy in clinical settings is a noninvasive application and has no serious complications or side effects. It may be an acceptable treatment of choice in many types of clinical procedures involving maxillofacial bones. Key words: bone healing; bone remodeling; fracture; low-intensity ultrasound; maxillofacial surgery; orthopedic surgery; therapeutic ultrasound.
Abbreviations BMU, basic multicellular unit; LIPU, low-intensity pulsed ultrasound
Received November 24, 2008, from the Department of Dental Services, Diyarbakır Military Hospital, Diyarbakır, Turkey (Ö.E.); and Department of Oral and Maxillofacial Surgery, Cukurova University, Faculty of Dentistry, Adana, Turkey (E.E.). Revision requested January 6, 2009. Revised manuscript accepted for publication February 4, 2009. We thank Yakup Üstün, DDS (School of Dentistry, Cukurova University), for encouraging us to prepare the manuscript. Address correspondence to Özgür Erdogan, DDS, PhD, 100 Yil Mahallesi 85337, Sokak 4-7, 01360 Seyhan-Adana, Turkey. E-mail: email@example.com
Article includes CME test
one is dynamic tissue, which is affected by many systemic and local factors. Bone healing is associated with a variety of biochemical, biomechanical, cellular, hormonal, and pathologic events. Numerous therapeutic methods for bone healing have been described in the literature. These applications include systemic and local drug delivery and physical treatments such as low-intensity lasers, electromagnetic fields, extracorporeal shock, mechanical stimulation, and ultrasound therapy.1 The use of ultrasound as a therapeutic approach in bone healing has a history of more than half a century. In this article, the current understanding of the molecular mechanisms of ultrasound therapy is discussed, the findings of the literature are surveyed, and the future of the application is evaluated. Maxillofacial bones may differ from extremity bones by their healing mechanisms.2 Therefore, research regarding maxillofacial bones was evaluated separately from that regarding other bones of the skeleton.
© 2009 by the American Institute of Ultrasound in Medicine • J Ultrasound Med 2009; 28:765–776 • 0278-4297/09/$3.50
and arthritis. The author created bilateral osteotomies in the radii of 3766 month-old rabbits. In the same year. and they reported that ultrasound treatment led to periosteal callus formation in 8 patients.5 W/cm2 stimulated new callus formation along the fracture line in the radial bones of rabbits. 1. cats.9 That was a cornerstone in this area because for the first time the positive effects. Lynn and Putnam7 described the equipment. and myalgia. Halsscheidt et al8 reported a case of osteomyelitis in the alveolar bone in a patient who had received ultrasound treatment for a lesion in the lower lip. Shiro12 advocated the use of lower doses and a pulsed ultrasound application.5. In an attempt to reduce the thermal damage to bone and stimulate bone growth. the general recognition was that ultrasound caused damage.5 The feasibility of generating focused ultrasound beams was shown by Gruetzmacher6 in 1935. Dyson and Brookes13 used a bilateral fibula osteotomy model in rabbits and applied ultrasound at an intensity of 0. in 1944. showed that continuous wave ultrasound at 800 kHz and 1. They reported 70% healing after a daily 20-minute ultrasound application. and monkeys. Two years later. and they applied LIPU (a 1. and its use in bones was to be avoided. Using this principle. Pilla et al16 osteotomized the tibias of rabbits bilaterally. but not the harmful effects.7 It resulted in the development of more sophisticated ultrasound devices to be used as surgical cutting and ablation tools in the following decades. or 2. In a placebo-controlled study. The authors claimed that ultrasound therapy was most effective in the early phase of bone healing. lower doses led to new periosteal bone formation. One limb of the rabbits received ultrasound treatment at 0.2 W/cm2 and reported increased osteoblastic/chondroblastic activity in osteotomized tibias of rabbits in the experimental group. The author used pulsed ultrasound at an intensity of 0. The daily ultrasound treatment was 10 minutes.5 W/cm2. According to the histologic and radiologic evaluations. The first study regarding the effects of ultrasound on bone healing was published in 1950 by Maintz. After that study. when they realized that some crystals produce acoustic waves if alternating current electricity is applied to them at their resonance frequency. which produced high-intensity focused ultrasound beams.10 two investigators from Italy. One of the pioneers in this area from Germany. 28:765–776 . He used ultrasound beams transmitted through the head to locate brain tumors and cerebral ventricles.2. Corradi and Cozzolino. Up through the 1950s. including sciatica. neuralgia. of ultrasound on bone were shown. Pohlman used ultrasound for the treatment of back pain. Ménière disease.5. the authors used ultrasound in a clinical application.3 The first official report of a diagnostic application of ultrasound was published in 1942 by Dussik. they showed irreversible thermal damage in the brains of dogs.4 a neurologist at the University of Vienna. Xavier and Dauarte14 applied lower doses of ultrasound (30 mW/cm2) to 26 patients with lower extremity fractures and nonunions after conventional treatments.Ultrasound Therapy in Bone Healing Historical Perspective The piezoelectric effect was discovered by Jacques and Pierre Curie in 1880. After this study. ultrasound was used as a therapeutic tool in the treatment of many diseases. In 1949. Twenty years after Shiro’s study.5-MHz pressure wave administered in pulses of 200 microseconds with an average temporal and spatial intensity of 30 mW/cm2) to rabbits in the experimental group.11 It was the first clinical application of therapeutic ultrasound to stimulate fracture healing. He reported improvement in symptoms when ultrasound at a frequency of 800 kHz and an intensity of 4 to 5 W/cm2 was applied to biological tissues for 10 days. it was concluded that although ultrasound treatment at high intensities caused thermal damage in bone. About the interaction of ultrasound with bone tissue. Although this dose of ultrasound treatment creates some increase in heat. it did not cause any kind of thermal injury. Duarte15 showed an ossification increase of 28% in osteotomized fibulas of rabbits that received low-intensity pulsed ultrasound (LIPU) compared with the control group. The authors showed that the osteotomized legs in the LIPU group gained the mechanical propJ Ultrasound Med 2009. The study showed an increase in ossification in the experimental group compared with the control group.2 The therapeutic use of ultrasound in medicine was first reported by Pohlman3 in 1939.5 W/cm2 to one side. 1. Using this equipment. neuralgia.
whereas the osteotomized legs in the control group gained the mechanical properties of the nonosteotomized legs on the 28th day.17 Three years later. and the formation of bone tumors. and 34 constituted the control group. which allow home application by the patient.22–25 Currently. the regeneration process of the skeleton after an injury or surgery. J Ultrasound Med 2009.29 In the inflammatory stage. The fractures treated at 50 mW/cm2 had significantly higher torsional stiffness and maximum torque when compared with the nontreated side. Tsai et al20 showed greater mineral apposition rates in rabbit fibulas 2 and 3 weeks after fractures that had been treated with 1.26 In 2000.27 The 3 types of ossification occur throughout the formation of new bones. In that multicenter study of 67 patients. Thus. ingrowth of vascular tissue occurs. are available on the market. the differences in these biomechanical parameters did not show any statistical significance in fractures treated at 100 mW/cm2. closed. closed. Azuma et al21 applied LIPU stimulation to experimental fracture sides at 4 different times from the 1st day through the 24th day. and the late remodeling stage. and inflammatory cells and fibroblasts infiltrate the injured area. To determine the best timing of LIPU therapy in a closed femoral fracture model. fibroblasts serve as stroma for vascular ingrowth.28 Bone or fracture healing may be defined as the repair of injured bone. and callus tissue consequently develops. calcification surrounding the organic matrix (intramembranous ossification).5 MHz repeating at 1 kHz with an average temporal and spatial intensity of 50 or 100 mW/cm2 to 1 fracture in each limb. The authors reported that LIPU accelerated fracture healing at a rate of 38%. For that purpose. and grade 1 open tibial diaphysis fractures in skeletally mature individuals when these fractures are orthopedically managed by closed reduction and cast immobilization. They are responsible for synthesis of the collagen matrix and angiogenesis. the indications were expanded to include treatment of established nonunions. The use of LIPU devices was initially cleared for marketing by the US Food and Drug Administration in 1994 for treatment of fresh. fresh. The average healing time for the fractures in the experimental group was 61 days. both using an intensity of 500 mW/cm2. However. The first randomized double-blind controlled study regarding the effects of LIPU on fresh tibia fractures in humans was published by Heckman et al17 in 1994. The animals in the experimental group received an ultrasound signal consisting of a 200-microsecond sine wave burst of 0.30 767 . Yang et al19 created bilateral closed femoral fractures in rats. or biomechanical parameters among the 4 groups. and posteriorly displaced distal radius fractures and fresh. or formation of new bone on existing bone (appositional ossification). It has 3 distinct but overlapping stages.5-MHz compared with 3-MHz ultrasound. Granulation tissue forms. In the repair stage.Erdogan and Esen erties of the nonosteotomized legs on the 17th day. histologic. excluding the skull and vertebrae. hematoma develops. The collagen matrix ossifies. the repair stage. and old fractures led to the use of this application in other orthopedic surgical protocols that involve bone healing. They showed that LIPU treatment resulted in accelerated fracture healing in each group regardless of the treatment timing. Bone Healing and Interaction of Ultrasound With Bone Tissue Bone formation may occur through transformation from cartilage tissue (endochondral ossification). These are the early inflammatory stage. 28:765–776 Successful reports of LIPU therapy in the management of closed. Bone healing is completed during the remodeling stage. Numerous studies have sought to determine the optimal ultrasound therapy regimen for stimulating fracture healing. Positive effects of LIPU have been shown in the management of spinal fusion and distraction osteogenesis procedures in rabbits. The results of that study imply that LIPU treatment accelerates all phases of fracture healing rather than any specific stage. commercial therapeutic ultrasound devices. and mesenchymal cells migrate in this stage. whereas the healing time in the control group was 98 days. 33 patients received LIPU treatment. Kristiansen et al18 reported accelerated healing of fresh dorsal radius fractures with LIPU treatment. there were no differences in radiologic.
ter Haar et al34 showed that ultrasound signals at a frequency of 1. Ultrasound application generates the piezoelectric effect in bone.36 Piezoelectric Effect An increase in electrical potential occurs when pressure is applied on bone tissue.Ultrasound Therapy in Bone Healing Woven bone is differentiated from lamellar bone. and direct effects to cell membranes. The energy attenuated by tissues leads to a thermal increase. when penetrating into tissues. as low as 20 to 50 mW/cm2. and the associated connective tissues. Acoustic streaming is defined as eddying of fluid near a vibrating structure such as a stable cavitation gas bubble. Stable cavitation defines the presence of gas bubbles in fluids due to ultrasound energy. the entire BMU moves forward.32 Because of these motions. and osteoclasts resorb bone and die by apoptosis. Ultrasound signals at high intensities create considerable heat increases. These cells act within a temporary anatomic structure called the basic multicellular unit (BMU). ultrasound treatment produces a micromassage effect in tissues. A combination of physical. and it is assumed that nonthermal effects of ultrasound are usually accompanied by some heat increase. It has been shown that ultrasound application increases ion conductibility up to 22% and decreases the need for adenosine triphosphate consumption by sodium-potassium channels.37 The piezoelectric effect induces bone resorption and bone healing.31. It is suggested that an increase in the electrical potential induces bone remodeling.39 J Ultrasound Med 2009. piezoelectric. it has been suggested that this small increase in temperature may affect some enzymes such as matrix 768 metalloproteinase 1. thus increasing the electrical potential within the tissue. Physical Effects Ultrasound waves generate vibrations in all tissue components. These mechanisms cause movement and transfer of intracellular and extracellular ions. This effect is called the piezoelectric effect. There is a close anatomic and functional relationship between resorptive and formative cells at remodeling sites. which is negligible in terms of thermal damage. Vibrations at these intensities generate a heat increase of less than 1°C.35 resulting in localized high-velocity streams of fluid created by ultrasound signals in a liquid. They cause movements or displacements of particles when transmitted in tissues.33 It is known that this enzyme is very sensitive to small variations in temperature. This movement in the fluid is called microstreaming. In the remodeling process. much is known today about the mechanism of action of ultrasound therapy. blood supplies.32 These bubbles may be in different shapes and sizes depending on the type of ultrasound signal and may lead to local movement in the fluid. The thermal and nonthermal effects of ultrasound are not separable. The observed nonthermal effects of ultrasound are stable cavitation. However. and biological effects of ultrasound plays a role in the interaction of ultrasound with bone healing. and the bone gains its original strength after completion of this stage. The primary cells involved are osteoblasts and osteoclasts.27 A mature BMU consists of a leading front of osteoclasts followed by osteoblasts. Despite the complex characteristics of bone healing and multiple effects of ultrasound on biological tissues.5 MHz and an intensity of 150 mW/cm2 generated bubbles bigger than 10 mm in body fluids of guinea pigs. including intracellular and extracellular fluids and cell membranes. 28:765–776 . Bone as dynamic living tissue remodels itself according to environmental forces. An increase in intercellular ion transfer leads to changes in membrane permeability. Acoustic vibrations have thermal and nonthermal effects in biological tissues. Remodeling of bone is regulated by a combination of resorption and bone formation. acoustic streaming. thereby assisting fracture healing. Several theories have been proposed to explain the mechanisms and effects. thus resulting in alterations of the electrophysiologic properties of the cells. The resorbed bone is replaced by newly formed bone. microstreaming. This remodeling action theory was explained by Wolff’s law38 in the 19th century. the therapeutic ultrasound used for bone healing uses low intensities. However. which produces mechanical stimulation.
The number of chondrocytes or osteoblasts has not been shown to be increased by ultrasound application.30 It has been shown that ultrasound application increases synthesis of angiogenesis-related cytokines such as interleukin 8.50 Treatment of delayed unions 769 . A nonunion is defined as cessation of healing for more than 3 months.40–43 Ultrasound signals induce conformational changes in the cell membrane and alter ionic permeability and second messenger activity. J Ultrasound Med 2009. These studies confirm that the impact of ultrasound on angiogenesis-related physiologic events has a major role in the enhanced bone healing process associated with ultrasound therapy. osteoporosis. and smoking habits.48 A power Doppler ultrasound–based study showed that low-intensity ultrasound delivered over a 10-day period stimulated a greater degree of vascularity at the sites of ulnar osteotomies in dogs. Many clinical studies regarding the effects of ultrasound treatment on bone healing have been based on fresh fracture models.17. which causes an increase in bone healing. usually near the fracture site.and bonespecific genes. and vascular endothelial growth factor. and several other mechanisms of action at the cellular level will possibly be discovered in the near future. In vitro studies on human and animal cell cultures showed several cellular effects of ultrasound application. resulting in an acceleration of the fracture repair process by up-regulating cartilage.Erdogan and Esen Biological Effects As ultrasound signals travel in bone. There are many in vivo and in vitro studies available regarding the biological effects of ultrasound application on bone healing. formation of new capillaries. 28:765–776 According to studies concerning the mechanism of bone healing stimulation by ultrasound therapy. fibroblast growth factor.45 Other documented effects of LIPU application on bone healing include increased expression of transforming growth factor β.21. It may be concluded that the fracture callus gains its original strength with ultrasound therapy in a shorter period by faster maturation of chondrocytes.49 Although fresh fractures heal mostly without complications with standard fracture care. Physiologic events related to maturation of chondrocytes and osteoblasts. and increased calcium ion incorporation.50 A delayed union corresponds to a slower healing process than expected. that are necessary for the normal healing process. An open fracture is defined as one in which there is communication with a break in the integument.44.25 These studies revealed that ultrasound application stimulates chondrocyte proliferation or maturation. such as growth factors and cytokines.19.46. Changes in second messenger activity lead to downstream alterations in gene expression. a biological response develops in the tissue. Clinical Applications Currently. and an increased rate of cell turnover activities in the repair zone are associated with physical and biological actions of ultrasound energy. the clinical use of ultrasound for bone healing mostly concerns fracture management. and increases platelet-derived growth factor synthesis. which possibly may be related to acceleration of bone healing or fracture repair. LIPU treatment may be considered for the management of fresh closed fractures in patients with conditions associated with bone metabolism such as diabetes. It has been shown that LIPU application stimulates aggrecan messenger RNA expression and proteoglycan synthesis by chondrocytes. the effects of ultrasound on bone tissue repair are not caused by a single mechanism. Clearly. steroid therapy.47 The rate of angiogenesis is one of the basic elements in the bone healing process. increases prostaglandin E2 synthesis by osteoblasts. the general consensus is that ultrasound application mainly affects endochondral bone formation. Ultrasound treatment has been shown to reduce the healing time of fresh fractures of tibial.18. Capillary formation occurs in the injured area in the inflammatory phase of bone healing. and scaphoid bones. More studies are needed to understand these mechanisms.45 Increased blood flow to the fracture site promotes delivery of the key components. as documented by serial radiographs including multiple views. distal radius. increased efflux of potassium ions from intracellular spaces.
53 21 patients with osteoarthritis underwent bilateral tibial hemicallotasis.58 In vitro studies conducted on mandibular osteoblast and fibroblast cultures showed that ultrasound signals increased proliferation of cells. no clinical study has been reported to date. With application of LIPU. There are few clinical studies showing positive effects of LIPU on distraction calluses. two different study groups published several in vivo and human studies regarding the effects of ultrasound on maxillofacial bones. the number of studies involving maxillofacial surgery has been limited. Management 770 of fractures is complicated in these patients for that reason. synthesis of cytokines such as interleukins and fibroblast growth factor. J Ultrasound Med 2009. and more clinical studies are needed in this area. The author applied ultrasound at 3 MHz and 1 W/cm2 for 40 days for the treatment of osteoradionecrosis of the mandible. El-Bialy et al60–64 showed enhanced bone formation at the callus tissue of mandibular distraction osteogenesis in rabbits. 28:765–776 . Another study by El-Mowafi and Mohsen54 showed accelerated healing of tibial distraction calluses in LIPU-treated patients. metatarsal.6 W/cm2 in rabbit mandibular fractures and reported a stimulated reparative process at the fracture site. Complete healing was shown in 86% of patients in an average of 22 weeks. Ultrasound treatment has been found beneficial in the treatment of delayed unions and nonunions. In a study by Tsumaki et al. The first in vivo study in this area was published by Fedotov et al57 in 1986. A report by Cavaliere56 may be considered the first report of the clinical application of ultrasound for enhancing maxillofacial bone healing. The authors showed increased callus bone mineral density in the LIPU-treated limbs. The efficacy of LIPU treatment on open fractures has not been proved by randomized clinical trials so far. One limb of every patient received a 20-minute ultrasound treatment daily for 4 weeks. no clinical use has been reported. scaphoid. this patient group constitutes the major group needing ultrasound therapy. Spinal arthrodesis is another orthopedic procedure in which LIPU treatment may be advantageous.2 to 0. Evidence of acceleration of bone healing in delayed unions and nonunions is weaker compared with treatment for fresh closed fractures of long bones because of the designs of the published studies. and the results have been controversial.42. Nolte et al52 applied the treatment to 29 patients with nonunions after conventional therapies. Although it was shown that ultrasound treatment stimulated bone growth in tantalum implants in dogs.Ultrasound Therapy in Bone Healing and nonunions may be complicated because of systemic and local conditions such as osteoporosis and radiotherapy. which are important mediators in angiogenesis and bone healing. Mayr et al51 used the application in 951 patients with delayed unions and 366 patients with nonunions. They reported successful healing in more than 86% of the patients in both groups. implant osseointegration is impaired in osteoporotic patients. However. and clavicle. better repair of orthodontically induced root resorption in humans. Another clinical report regarding ultrasound therapy in maxillofacial bones was published by Harris58 in 1992. enhanced mandibular growth in rabbits. Clinical studies mainly favor LIPU treatment for distraction osteogenesis procedures.59 Beginning in 2002. Another clinical procedure in which ultrasound therapy has been used is distraction osteogenesis. radius/ulna. the numbers of studies and patients have been limited. They used ultrasound treatment at 0. and synthesis of nitric oxide and prostaglandins. However. Although several animal studies showed positive effects of LIPU treatment on spinal arthrodesis procedures. humerus. The fractures were located in the tibia. He found positive progress in 10 of 21 patients. enhanced mandibular incisor growth and eruption in rabbits. Because of an altered bone turnover rate. femur.55 Ultrasound Therapy and Maxillofacial Bones Most studies regarding the effects of ultrasound therapy on bone healing have been conducted on long bones. He applied ultrasound at relatively high intensities (1–2 W/cm2) to 4 patients with mandibular fractures and reported increased calluses and decreased pain with the use of ultrasound therapy.
The data showed increased callus healing compared with other groups for the continuous mode in the first 2 weeks and the pulsed mode in the third and fourth weeks. They showed no effect of LIPU treatment on mandibular bone defects either covered with a polytetrafluoroethylene membrane. The intensity of the ultrasound output was 30 mW/cm2. covered with a collagen membrane. Ikai et al72 studied periodontal wound healing and bone repair after LIPU treatment.70 However. They applied LIPU to one side and evaluated the bone healing using histologic analysis and immunohistochemical studies.25 The fact that maxillofacial bones have intramembranous ossification makes the use of ultrasound therapy questionable in this particular region. However.Erdogan and Esen and enhanced mandibular growth in growing baboons when ultrasound treatment was combined with functional appliances. and the effectiveness of ultrasound therapy in this area should be clearer in the coming years. however. whereas the second group received continuous ultrasound at the same intensity. A list of previous animal and clinical studies involving the maxillofacial bones is given in Table 1. and scaphoid bone regions. Shortening the intermaxillary fixation time may be a main indication for LIPU applications in the maxillofacial area. Although the absolute dimension of bone volume was not affected by the ultrasound therapy. One group received pulsed ultrasound therapy at 30 mW/cm2. As with the management of fractures of the long bones. Kerr et al71 evaluated the effects of ultrasound therapy in socket preservation after tooth extraction. 28:765–776 They reported accelerated new bone formation on the LIPU-treated sides. The pulse status of the ultrasound transmission. was not specified in the article. No serious complications have been reported regarding the clinical use of therapeutic ultrasound. in which the effects of ultrasound are not known. El-Bialy et al73 investigated the effects of pulsed and continuous ultrasound therapy on distraction osteogenesis in rabbit mandibles. 2 clinical articles published by Schortinghuis et al68. This makes penetration of ultrasound signals weaker. Pulsed signals and low energy minimize the thermal effects of ultrasound on biological tissues. and eyes. ulnar. The third group received sham treatment. It is mainly accepted that ultrasound treatment enhances endochondral bone formation. There were no differences between the groups for root resorption and gingival recession. They prepared acrylic stents for each patient and applied ultrasound via the stents to one side after tooth extraction in a split-mouth manner. Most maxillofacial fractures require intermaxillary fixation.69 reported no notable contribution of LIPU treatment to mandibular vertical osteogenesis procedures. another series by Schortinghuis et al65–67 showed contrary results. which is comparable to diagnostic ultrasound doses. One animal study conducted on rabbits showed increased fracture healing in a mandibular fracture model. and a long fixation duration causes many problems such as feeding impairment. Some other recent studies showed positive effects of ultrasound therapy associated with oral surgery. or left uncovered in rats. They used 36 rabbits divided into 3 groups. more studies are needed to determine the optimal dosing and treatment modality before using this procedure in clinical settings. Reported 771 . More studies lie ahead to be conducted.21. the treatment of maxillofacial fractures may be problematic for both the patient and the surgeon. parotid gland. which has a critical role in dental implant placement. The close relationship to important anatomic structures such as the brain. However. Similarly. is another drawback for use in maxillofacial bones. an increased interest in the therapeutic use of ultrasound for oral and maxillofacial surgical protocols is apparent in the literature. Complications and Side Effects Ultrasound treatment for bone healing generates low-intensity energy. and dental/periodontal problems. thus reducing the effectiveness of the treatment. some increase in buccal height was found at the bone crest level and 3 mm apical to the crest level. They created bone defects intraorally at the root level of premolar teeth in 4 beagles bilaterally. temporomandibular joint problems. Immunochemical analysis showed expression of heat shock protein 70–positive cells in the LIPU-treated wounds. Another drawback is the thicker soft tissue layer compared with tibial. J Ultrasound Med 2009.
total 13 h ultrasound exposure 1.57 1986 Harris. Clinical and Animal Studies Concerning the Effects of Ultrasound Therapy on Maxillofacial Bones Study Indication 56 Animal/Clinical (No.5 MHz. Treatment Time Conclusions Cavaliere. pulsed.5 MHz. 30 mW/cm2. less pain Stimulated reparative process at fracture site Effective treatment in 48% of patients Enhanced bone formation at the distraction site Enhanced mandibular incisor growth and eruption Enhanced mandibular growth Decrease in root resorption No notable benefit of ultrasound treatment No notable benefit of ultrasound treatment No notable benefit of ultrasound treatment No stimulation of bone formation at the distraction gap Enhanced mandibular growth in growing baboons when ultrasound treatment was combined with functional appliances Stimulated reparative process at fracture site No evidence of accelerated callus healing by ultrasound treatment compared with control group No notable effect on overall bone volume. pulsed. 46 ± 8.61 2003 El-Bialy et al. 4 mo Increased callus tissue.Ultrasound Therapy in Bone Healing adverse effects due to ultrasound treatment include muscle spasms on the treatment side. pulsed.5 MHz. 2 or 4 wk 1. however.58 1992 El-Bialy et al. pulsed.5 MHz. 2 or 4 wk 1. of Subjects) Ultrasound Frequency.62 2003 El-Bialy et al. pulsed. 10–15 d 0.72 2008 Ossification around bony defect created at the mesial root of premolar tooth Beagles (4) 1.67 2005 Schortinghuis et al. pulsed.1 d Kerr et al. 30 mW/cm2. increase in level of expression of heat shock protein 70 Increased callus healing by continuous mode in the first 2 wk and by pulsed mode in 3rd and 4th wk Rats (64) Clinical (8) Mandibular growth modification Baboons (14) Erdogan et al. 3 wk 1. 1957 Fedotov et al.66 2004 Schortinghuis et al.69 2008 Vertical mandibular distraction osteogenesis Rabbits (30) Clinical (9) 1. 30 mW/cm2.5 MHz.47 It also has been shown that ultrasound signals do not interfere with metal objects.5 MHz.6 W/cm2.5 MHz.73 2008 Mandibular distraction osteogenesis Rabbits (36) 1. 30 mW/cm2.63 2004 Schortinghuis et al. 30 mW/cm2. pulsed or continuous. 4 wk El-Bialy et al. pulsed. 30 mW/cm2. and its use in sites with implanted metal biomaterial is safe. 30 mW/cm2. pulsed.5 MHz. pulsed. mild erythema. 10 sessions over 4 wk Ikai et al. pulsed. 30 mW/cm2. 1–4 wk 772 J Ultrasound Med 2009. pulsed. 4 wk 1. 2 or 4 wk 1.68 2005 El-Bialy et al. and mild swelling. 30 mW/cm2. 40 d 1.70 2006 Mandibular fracture Schortinghuis et al.2–0.64 2006 Mandibular fracture Mandibular fracture Osteoradionecrosis of mandible Mandibular distraction osteogenesis Effects on mandibular incisor teeth eruption Mandibular growth modification Effects on orthodontic root resorption Healing of mandibular defects Healing of mandibular defects covered with polytetrafluoroethylene membrane Healing of mandibular defects covered with collagen membrane Vertical distraction osteogenesis of the mandible Clinical (4) Rabbits (36) Clinical (21) Rabbits (21) Rabbits (15) 0. 30 mW/cm2.60 2002 El-Bialy et al. 5 min daily for 8 d 3 MHz. 4 wk 1.71 2008 Bone preservation at extraction socket Clinical (12) 30 mW/cm2 (frequency and pulse status not specified).7–1 MHz.65 2004 Schortinghuis et al.5 MHz. 4 wk 1. 4 wk 2 Rabbits (8) Clinical (12) Rats (72) Rats (72) 1. Intensity. 30 mW/cm2. pulsed.5 MHz.5 MHz. 30 mW/cm2 .5 MHz. 30 mW/cm2. pulsed. 28:765–776 . pulsed. 1–2 W/cm . 1 W/cm2. increased buccal height at the bony crest as well as apical to the crest Accelerated periodontal wound healing and bone repair.5 MHz.55 One disad- Table 1.
Its use in sites with suspected neoplasia and acute infections is contraindicated because of possible accelerated disease progression. Although it does not seem possible to treat osteoporosis itself because of application difficulties and a low penetration rate. Integration of biomaterials may be impaired in osteoporotic patients. which develops as a consequence of radiotherapy. especially in developed countries with large elderly populations. Thus. such as spinal arthrodesis and distraction osteogenesis. Patients should be evaluated for allergic reactions to the coupling gel. Tanzer et al55 showed increased bone growth in porous intramedullary tantalum implants in the ulnas of dogs. However.48 One study showed that supportive ultrasound application helped considerably for the treatment of osteonecrosis of jaws. its use in pediatric patients and in skull bones should be avoided. In such situations.52 One main indication for ultrasound treatment may be this group of patients in the future. Future of Ultrasound Therapy for Bone Healing Minimal complication rates and adverse effects of ultrasound therapy for acceleration of bone healing made it possible to use this therapy in clinical settings.58 Ultrasound therapy may be considered a supportive treatment option for osteonecrosis.51.Erdogan and Esen vantage of home application of ultrasound is patient dependency on the treatment. There is evidence of successful treatment of nonunions and delayed unions with LIPU therapy. its use for acceleration of osseointegration of metal biomaterials in osteoporotic patients has a promising future in orthopedic surgery and oral-maxillofacial surgery. The conventional treatment approach is surgical debridement with additional antibiotic and hyperbaric oxygen therapy. It is an acceptable treatment of choice in fractures with delayed unions and nonunions. patient cooperation affects the success of the therapy. Experimental and clinical studies are being conducted continuously to elucidate the mechanisms of action and effectiveness of ultrasound therapy in clinical settings. Osteoporosis is a major disease affecting bone tissue. Although much is known about 773 . It has been shown that ultrasound treatment positively affects soft tissue wound healing as well. ultrasound therapy may be considered as an alternative treatment. It has been shown that ultrasound treatment increases vascularity by inducing synthesis of angiogenesis-related cytokines. It is characterized by hypoxia and hypovascularity.74 Complicated fractures that involve soft tissue and bone injury combined may benefit from ultrasound therapy. Although there are many clinical and animal studies available showing positive effects of ultrasound. The effects of ultrasound therapy on growing bones and brain tissue are not clear. and patients with cardiac pacemakers should avoid ultrasound treatment because of possible interaction with the ultrasound signals. J Ultrasound Med 2009. Therapeutic ultrasound in clinical settings is a noninvasive application and has no known serious complications or side effects.45. Although current indications for use in clinical settings may be limited to a small group of patients. controversial results exist as well. Most fresh fractures and surgical approaches associated with bone tissue heal uneventfully with conventional treatments. Conclusions The use of ultrasound in medicine was initially developed for therapeutic rather than diagnostic purposes. More animal and clinical studies are needed in this area. Its use in the treatment of fresh fractures and surgical interventions associated with bone tissue. 28:765–776 Osteoradionecrosis is avascular necrosis of bone. One potential use of ultrasound is as a supportive therapeutic procedure after reconstructive surgery at sites that receive radiotherapy. in healthy patients may not be worthwhile because bone healing usually occurs in these situations. ultrasound therapy may be an important treatment option in the management of the bone injuries and diseases mentioned above. One potential use of ultrasound treatment is to accelerate osseointegration of implants (fracture management and dental implants) in osteoporotic patients. Hypovascularity and hypoxia due to radiotherapy impair the success of reconstructive procedures in oncologic surgery. in cases in which faster healing is desired by the patient or the physician.
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