Low-Intensity Pulsed Ultrasound Accelerates Rat Femoral Fracture Healing by Acting on the Various Cellular Reactions in the Fracture Callus

Abstract

Low-intensity pulsed ultrasound (LIPUS) has been shown to accelerate fracture healing in both animal models and clinical trials, but the mechanism of action remains unclear. In fracture healing, various consecutive cellular reactions occurred until repair. We investigated whether the advanced effects of LIPUS depended on the duration and timing of LIPUS treatment in a rat closed femoral fracture model to determine the target of LIPUS in the healing process. Sixty-nine Long-Evans male rats that have bilateral closed femoral fractures were used. The right femur was exposed to LIPUS (30 mW/cm 2 spatial and temporal average [SATA], for 20 minutes/day), and the left femur was used as a control. Rats were divided into four groups according to timing and duration of treatment (Ph-1, days 1-8; Ph-2, days 9 -16; Ph-3, days 17-24; throughout [T], days 1-24 after the fracture). Animals were killed on day 25. After radiographs and microfocus X-ray computed tomography (CT) tomograms were taken, the hard callus area (HCA), bone mineral content (BMC) at the fracture site, and mechanical torsion properties were measured, and histological analysis was conducted. Interestingly, the maximum torque of the LIPUS-treated femur was significantly greater than that of the controls in all groups without any changes in HCA and BMC. The multiviewing of three-dimensional (3D) CT reconstructions and histology supported our findings that the partial LIPUS treatment time was able to accelerate healing, but longer treatment was more effective. These results suggest that LIPUS acts on some cellular reactions involved in each phase of the healing process such as inflammatory reaction, angiogenesis, chondrogenesis, intramembranous ossification, endochondral ossification, and bone remodeling. (J Bone Miner Res 2001;16:671-680)

Curative Effect of Combined Treatment With Alendronate and 1 α-Hydroxyvitamin D3 on Bone Loss by Ovariectomy in Aged Rats

“…(Osaka) as previously described (46). Femur specimens were evaluated at the midportion and at 10 mm from the distal end by cross-sectional analysis.…”

Low‐level accelerations applied in the absence of weight bearing can enhance trabecular bone formation

“…Confining the anabolic response to weightbearing bones excludes skeletons incapable of bearing weight (e.g., patients with spinal injuries or muscular dystrophy) or clinically important sites not associated with weight bearing (e.g., distal radius). Considering that electric fields, 24,25 intramedullary pressure, 26 and ultrasound 27,28 can all effectively promote bone formation and fracture healing, the direct application of matrix deformations may not be a required component for WBV to be efficacious.…”

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“…These results determined that LIPUS have a significant effect on the earlier inflammatory or accelerate to callus formation phases of healing. [22,31,[73][74][75] In a study with a rat femoral fracture model, hard callus area, bone mineral content, mechanical torsion properties were measured at 4 different periods (1-8 days, 9-16 days, 17-24 days, 1-24 days) after expose to LIPUS, along with histologic analysis. The findings reported statistically significant increases in all measured parameters in all groups when compared with the control group.…”

“…They suggested that LIPUS acts on some cellular reactions at each stage of the fracture healing process. [73] Azuma et al (2001) in an experimental study measured mechanical and histological changes at different time periods during the healing process. They investigated the timing or duration of stimulation effect after 8 and 25 days of LIPUS treatment.…”