Investigation of rat bone fracture healing using pulsed 1.5 MHz, 30 mW/cm(2) burst ultrasound--axial distance dependency.

This study investigated the effect of LIPUS on fracture healing when fractures were exposed to ultrasound at three axial distances: z=0 mm, 60 mm, and 130 mm. We applied LIPUS to rat fracture at these three axial distances mimicking the exposure condition of human fractures at different depths under the soft tissue. Measurement of LIPUS shows pressure variations in near field (nearby transducer); uniform profile was found beyond it (far field). We asked whether different positions of the fracture within the ultrasound field cause inconsistent biological effect during the healing process. Closed femoral fractured Sprague-Dawley rats were randomized into control, near-field (0mm), mid-near field (60 mm) or far-field (130 mm) groups. Daily LIPUS treatment (plane, but apodized source, see details in the text; 2.2 cm in diameter; 1.5 MHz sine waves repeating at 1 kHz PRF; spatial average temporal average intensity, ISATA=30 mW/cm(2)) was given to fracture site at the three axial distances. Weekly radiographs and endpoint microCT, histomorphometry, and mechanical tests were performed. The results showed that the 130 mm group had the highest tissue mineral density; and significantly higher mechanical properties than control at week 4. The 60 mm and 0 mm groups had significantly higher (i.e. p<0.05) woven bone percentage than control group in radiological, microCT and histomorphometry measurements. In general, LIPUS at far field augmented callus mineralization and mechanical properties; while near field and mid-near field enhanced woven bone formation. Our results indicated the therapeutic effect of LIPUS is dependent on the axial distance of the ultrasound beam. Therefore, the depth of fracture under the soft tissue affects the biological effect of LIPUS. Clinicians have to be aware of the fracture depth when LIPUS is applied transcutaneously.

[1]  W. Harvey,et al.  The stimulation of bone formation in vitro by therapeutic ultrasound. , 1997, Ultrasound in medicine & biology.

[2]  Y. Azuma,et al.  Effects of ultrasound and 1,25-dihydroxyvitamin D3 on growth factor secretion in co-cultures of osteoblasts and endothelial cells. , 2000, Ultrasound in medicine & biology.

[3]  E. Morgan,et al.  Correlations between indentation modulus and mineral density in bone-fracture calluses. , 2009, Integrative and comparative biology.

[4]  T. Kokubu,et al.  Low intensity pulsed ultrasound exposure increases prostaglandin E2 production via the induction of cyclooxygenase-2 mRNA in mouse osteoblasts. , 1999, Biochemical and biophysical research communications.

[5]  Peter Graham Fish Physics and Instrumentation of Diagnostic Medical Ultrasound , 1990 .

[6]  T. Einhorn,et al.  Production of a standard closed fracture in laboratory animal bone , 1984, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[7]  L. Qin,et al.  Changes of microstructure and mineralized tissue in the middle and late phase of osteoporotic fracture healing in rats. , 2007, Bone.

[8]  M. Bhandari,et al.  The effect of low-intensity pulsed ultrasound therapy on time to fracture healing: a meta-analysis. , 2002, CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne.

[9]  L. Qin,et al.  Low-magnitude high-frequency vibration treatment augments fracture healing in ovariectomy-induced osteoporotic bone. , 2010, Bone.

[10]  E. Morgan,et al.  Measurement of fracture callus material properties via nanoindentation. , 2008, Acta biomaterialia.

[11]  W. Cheung,et al.  Low Intensity Pulsed Ultrasound Stimulates Osteogenic Activity of Human Periosteal Cells , 2004, Clinical orthopaedics and related research.

[12]  R. Marti,et al.  Low‐intensity ultrasound stimulates endochondral ossification in vitro , 2001, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[13]  Gordon H Guyatt,et al.  Low intensity pulsed ultrasonography for fractures: systematic review of randomised controlled trials , 2009, BMJ : British Medical Journal.

[14]  F.L. Thurstone,et al.  Biomedical Ultrasonics , 1970, IEEE Transactions on Industrial Electronics and Control Instrumentation.

[15]  Walter H. Chang,et al.  Optimum intensities of ultrasound for PGE(2) secretion and growth of osteoblasts. , 2002, Ultrasound in medicine & biology.

[16]  L. Qin,et al.  Low‐magnitude high‐frequency vibration accelerates callus formation, mineralization, and fracture healing in rats , 2009, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[17]  L. Qin,et al.  Dose‐dependent effect of low‐intensity pulsed ultrasound on callus formation during rapid distraction osteogenesis , 2006, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[18]  H. Busk,et al.  In Vivo Ultrasonic Measurements of Tissue Properties , 1982 .

[19]  Kwok-Sui Leung,et al.  Effects of different therapeutic ultrasound intensities on fracture healing in rats. , 2012, Ultrasound in medicine & biology.

[20]  D Mitton,et al.  Mechanical properties of ewe vertebral cancellous bone compared with histomorphometry and high-resolution computed tomography parameters. , 1998, Bone.

[21]  J. Zemanek Beam Behavior within the Nearfield of a Vibrating Piston , 1971 .

[22]  K. Fung,et al.  Effect of Weightbearing on Bone Formation During Distraction Osteogenesis , 2004, Clinical orthopaedics and related research.

[23]  Kwok-Sui Leung,et al.  Complex tibial fracture outcomes following treatment with low-intensity pulsed ultrasound. , 2004, Ultrasound in medicine & biology.

[24]  M. Dyson,et al.  Stimulation of bone repair by ultrasound. , 1985, Ultrasound in medicine & biology.

[25]  Javad Parvizi,et al.  Exposure to low‐intensity ultrasound increases aggrecan gene expression in a rat femur fracture model , 1996, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[26]  Louis Yuge,et al.  Low-Intensity Pulsed Ultrasound Accelerates Osteoblast Differentiation and Promotes Bone Formation in an Osteoporosis Rat Model , 2009, Pathobiology.

[27]  E. Chao,et al.  Low intensity ultrasound treatment increases strength in a rat femoral fracture model , 1994, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[28]  S Meghji,et al.  Ultrasound stimulates nitric oxide and prostaglandin E2 production by human osteoblasts. , 2002, Bone.

[29]  R F Kilcoyne,et al.  Acceleration of tibial fracture-healing by non-invasive, low-intensity pulsed ultrasound. , 1994, The Journal of bone and joint surgery. American volume.

[30]  Y. Harada,et al.  Low‐Intensity Pulsed Ultrasound Accelerates Rat Femoral Fracture Healing by Acting on the Various Cellular Reactions in the Fracture Callus , 2001, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[31]  T. Einhorn,et al.  Application of Histomorphometric Methods to the Study of Bone Repair , 2005, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.