Scintigraphic control of bone-fracture healing under ultrasonic stimulation: An animal experimental study

Klug, W; Franke, W.‐G.; Knoch, Hans-Georg

doi:10.1007/bf00252796

Cited by 56 publications

(16 citation statements)

References 4 publications

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“…Its effectiveness has been demonstrated in numerous in vivo studies [1][2][3][4][5][6][7] and supported by in vitro examinations using cell culture systems. [8][9][10][11][12] LIPUS stimulation is a noninvasive, feasible, and economical method, and it has emerged as a safer alternative to biophysical approaches, especially for patients with bone plates or pacemakers.…”

Section: Introductionmentioning

confidence: 94%

Low-Intensity Pulsed Ultrasound Stimulation Enhances Heat-Shock Protein 90 and Mineralized Nodule Formation in Mouse Calvaria-Derived Osteoblasts

Miyasaka

Nakata

Jia

et al. 2015

Tissue Engineering Part A

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Low-intensity pulsed ultrasound (LIPUS) has demonstrated its positive effects on osteogenic differentiation of mesenchymal stem cells and the proliferation and differentiation of osteoblasts, negative effects on osteoclast growth, and promotion of angiogenesis, leading to improvement of the tissue perfusion. Heat-shock proteins (HSPs) are initially identified as molecules encouraged and expressed by heat stress or chemical stress to cells and involved in the balance between differentiation and apoptosis of osteoblasts. However, it remains unclear if the effect of LIPUS on osteoblast differentiation could involve HSP expression and contribution. In this study, mouse calvarial osteoblasts were exposed to LIPUS at a frequency of 3.0 MHz by 30 mW/cm 2 for 15 min or to 42°C heat shock for 20 min at day 3 of cell culture and examined for osteogenesis with pursuing induction of HSP27, HSP70, and HSP90. LIPUS as well as heat shock initially upregulated HSP90 and phosphorylation of Smad1 and Smad5, encouraging cell viability and proliferation at 24 h, enhancing mineralized nodule formation stronger by LIPUS after 10 days. However, HSP27, associated with BMP2-stimulated p38 mitogen-activated protein kinase during osteoblast differentiation, was downregulated by both stimulations at this early time point. Notably, these two stimuli maintained Smad1 phosphorylation with mineralized nodule formation even under BMP2 signal blockage. Therefore, LIPUS might be a novel inducer of osteoblastic differentiation through a noncanonical signal pathway. In conclusion, LIPUS stimulation enhanced cell viability and proliferation as early as 24 h after treatment, and HSP90 was upregulated, leading to dense mineralization in the osteoblast cell culture after 10 days.

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Section: Introductionmentioning

confidence: 94%

Low-Intensity Pulsed Ultrasound Stimulation Enhances Heat-Shock Protein 90 and Mineralized Nodule Formation in Mouse Calvaria-Derived Osteoblasts

Miyasaka

Nakata

Jia

et al. 2015

Tissue Engineering Part A

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“…These original findings were soon supported by Reuter et al [16,17], who found positive effects in bone in a series of animal studies that involved using a continuous ultrasound signal an order of magnitude higher than that used by Duarte [18]. Klug et al [19,20] demonstrated that ultrasound treatment delivered at an intensity of 200 mW/ cm 2 accelerated the healing of closed lower-extremity fractures in rabbits by 18%. Pilla et al [21], in a placebocontrolled study of midshaft tibial osteotomies in rabbits, found that brief periods (20 min/day) of pulsed ultrasound (a 200-μs burst of 1.5-MHz sine waves, repeated at 1 kHz), delivered at a low intensity of 30 mW/cm 2 , accelerated the recovery of torsional strength and stiffness.…”

Section: Discussionmentioning

confidence: 91%

The effect of ultrasound on the healing of muscle-pediculated bone graft in scaphoid non-union

Ricardo

2006

International Orthopaedics (SICO

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The use of pedicled vascularised bone grafts from the distal radius makes it possible to transfer bone with a preserved circulation and viable osteoclasts and osteoblasts. Experiments performed at the basic science level has provided substantial evidence that low-intensity ultrasound can accelerate and augment the fracture healing process. Only an adequate double-blind trial comparing treatment by ultrasound stimulation in patients treated by similar surgical techniques can provide evidence of the true effect of ultrasound. This paper describes the results of such a trial. From 1999 to 2004, 21 fractures of the scaphoid with established non-union treated with vascularised pedicle bone graft were selected for inclusion in a double-blind trial. All patients were males, with an average age of 26.7 years (range 17-42 years) and an average interval between injury and surgery of 38.4 months (range 3 months

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“…Fracture healing has been accelerated by exposure to a specific pulse of extremely low‐intensity pulsed ultrasound (LIPUS) in the latter power range in both animal fracture models and clinical trials (3–9) . For example, Heckman et al reported that LIPUS treatment for 20 minutes/day at 30 mW/cm 2 led to a significant 24% reduction in the time required for clinical healing in a prospective randomized placebo‐controlled study of closed or grade I open tibial fractures (8) .…”

Section: Introductionmentioning

confidence: 99%

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

Azuma

Ito

Harada

et al. 2001

Journal of Bone and Mineral Research

334

213

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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)

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Scintigraphic control of bone-fracture healing under ultrasonic stimulation: An animal experimental study

Cited by 56 publications

References 4 publications

Low-Intensity Pulsed Ultrasound Stimulation Enhances Heat-Shock Protein 90 and Mineralized Nodule Formation in Mouse Calvaria-Derived Osteoblasts

Low-Intensity Pulsed Ultrasound Stimulation Enhances Heat-Shock Protein 90 and Mineralized Nodule Formation in Mouse Calvaria-Derived Osteoblasts

The effect of ultrasound on the healing of muscle-pediculated bone graft in scaphoid non-union

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

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