Effect of Low‐Intensity Pulsed Ultrasound on Distraction Osteogenesis Treatment Time

Raza, Hasnain; Saltaji, Humam; Kaur, Harmanpreet; Flores-Mir, Carlos; El‐Bialy, Tarek

doi:10.7863/ultra.15.02043

Cited by 29 publications

(32 citation statements)

References 37 publications

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“…The positive effect of LIPUS on acceleration of bone regeneration in this systematic review are consistent with the results of a previous review on five human trials (four on tibia and one on a mandible) studying the effect of LIPUS during DO [40]. This review studied the optimal time for LIPUS applications, the appropriate intensity of LIPUS and the histological aspects including the ossification pattern, which could serve as a milestone for future studies investigating the biological mechanism of LIPUS on bone regeneration.…”

Section: Discussionsupporting

confidence: 86%

Low Intensity Pulsed Ultrasound for Accelerating Distraction Osteogenesis: A Systematic Review of Experimental Animal Studies

Ginini¹,

Shilo²,

Emodi³

et al. 2018

J. Mol. Clin. Med.

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The purpose of this report is to review systematically all studies performed regarding the influence of low intensity pulsed ultrasound (LIPUS) on bone regeneration in animals during distraction osteogenesis (DO). Based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist structure, a systematic search using PubMed and EMBASE electronic databases was undertaken utilizing the key words "distraction osteogenesis" and "low intensity ultrasound". Human trials, review articles, case reports and non-English language publications were excluded. Data items were extracted from each eligible study, regarding the study design, risk of bias, results and whether or not LIPUS accelerated bone regeneration. The search identified 40 relevant articles, 15 of which were included for full review. Included studies were characterized by a high risk of bias and considerable variations in study design was observed. However, most studies which reported LIPUS in an intensity of 30-40 mW/cm 2 accelerated bone formation via endochondral ossification, thus shortening the consolidation period when applied during distraction and early consolidation periods. According to the current review, application of LIPUS during DO shows promise in accelerating bone formation and density during DO, that bears no adverse effects, thus shortening the consolidation period. Optimal timing of LIPUS application is during the distraction and early consolidation phases. The preferred intensity should be between 30-40 mW/cm 2. Histological analysis indicates influence via endochondral ossification. Thus, the effect of LIPUS on chondrocytes should be further investigated in order to decipher the exact molecular and cellular influence of LIPUS on enhancement of bone formation. These findings should be used in future clinical protocols and raise potential directions for future research regarding the molecular mechanisms underlying the influence of LIPUS on bone formation.

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Section: Discussionsupporting

confidence: 86%

Low Intensity Pulsed Ultrasound for Accelerating Distraction Osteogenesis: A Systematic Review of Experimental Animal Studies

Ginini¹,

Shilo²,

Emodi³

et al. 2018

J. Mol. Clin. Med.

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“…Clinically, LIPUS was reported to accelerate bone maturation in DO, and reduce the overall time to removal of the fixation device in clinical trials [71] , [72] , [73] : El-Mowafi et al [71] indicated that the mean healing index in the ultrasound group was 30 (27–36) d/cm, as compared with the control group with 48 (42–75) d/cm in a 20-patient trial [71] ; Salem et al [72] reported 27% faster callus maturation and 33% more radiographic callus density in the LIPUS group in a 21-patient trial; Dudda et al [73] showed that the fixation gestation period was decreased for 43.6 days in the ultrasound group with no negative effects in a 36-patient trial. A meta-analysis report [20] , [74] concluded that LIPUS was an effective treatment to reduce the overall treatment time for DO, yet the lines of evidence were weak; thus, large-scale clinical studies are needed to confirm its efficacy.…”

Section: Distraction Osteogenesismentioning

confidence: 99%

Ultrasound as a stimulus for musculoskeletal disorders

Zhang

Chow

Leung

et al. 2017

Journal of Orthopaedic Translation

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SummaryUltrasound is an inaudible form of acoustic sound wave at 20 kHz or above that is widely used in the medical field with applications including medical imaging and therapeutic stimulation. In therapeutic ultrasound, low-intensity pulsed ultrasound (LIPUS) is the most widely used and studied form that generally uses acoustic waves at an intensity of 30 mW/cm2, with 200 ms pulses and 1.5 MHz. In orthopaedic applications, it is used as a biophysical stimulus for musculoskeletal tissue repair to enhance tissue regeneration. LIPUS has been shown to enhance fracture healing by shortening the time to heal and reestablishment of mechanical properties through enhancing different phases of the healing process, including the inflammatory phase, callus formation, and callus remodelling phase. Reports from in vitro studies reveal insights in the mechanism through which acoustic stimulations activate cell surface integrins that, in turn, activate various mechanical transduction pathways including FAK (focal adhesion kinase), ERK (extracellular signal-regulated kinase), PI3K, and Akt. It is then followed by the production of cyclooxygenase 2 and prostaglandin E2 to stimulate further downstream angiogenic, osteogenic, and chondrogenic cytokines, explaining the different enhancements observed in animal and clinical studies. Furthermore, LIPUS has also been shown to have remarkable effects on mesenchymal stem cells (MSCs) in musculoskeletal injuries and tissue regeneration. The recruitment of MSCs to injury sites by LIPUS requires the SDF-1 (stromal cell derived factor-1)/CXCR-4 signalling axis. MSCs would then differentiate differently, and this is regulated by the presence of different cytokines, which determines their fates. Other musculoskeletal applications including bone–tendon junction healing, and distraction osteogenesis are also explored, and the results are promising. However, the use of LIPUS is controversial in treating osteoporosis, with negative findings in clinical settings, which may be attributable to the absence of an injury entry point for the acoustic signal to propagate, strong attenuation effect of cortical bone and the insufficient intensity for penetration, whereas in some animal studies it has proven effective.

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“…6 7 8 9 10 11 12 13 14 Our systematic review, however, differs from previous systematic reviews in several important aspects. Firstly, we include the recently published TRUST trial,16 by far the largest trial on LIPUS treatment for bone healing, which reported a number of outcomes important to patients.…”

Section: Discussionmentioning

confidence: 80%

“…6 7 8 9 10 11 12 13 14 Because existing randomized controlled trials were limited by small sample size, risk of bias, inconsistent results, and failure to cover outcomes important to patients, no review offered definitive conclusions. All reviews identified the need for additional randomized controlled trials.…”

Section: Introductionmentioning

confidence: 99%

Low intensity pulsed ultrasound for bone healing: systematic review of randomized controlled trials

Schandelmaier

Kaushal

Lytvyn

et al. 2017

BMJ

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Objective To determine the efficacy of low intensity pulsed ultrasound (LIPUS) for healing of fracture or osteotomy.Design Systematic review and meta-analysis.Data sources Medline, Embase, CINAHL, Cochrane Central Register of Controlled Trials, and trial registries up to November 2016.Study selection Randomized controlled trials of LIPUS compared with sham device or no device in patients with any kind of fracture or osteotomy.Review methods Two independent reviewers identified studies, extracted data, and assessed risk of bias. A parallel guideline committee (BMJ Rapid Recommendation) provided input on the design and interpretation of the systematic review, including selection of outcomes important to patients. The GRADE system was used to assess the quality of evidence.Results 26 randomized controlled trials with a median sample size of 30 (range 8-501) were included. The most trustworthy evidence came from four trials at low risk of bias that included patients with tibia or clavicle fractures. Compared with control, LIPUS did not reduce time to return to work (percentage difference: 2.7% later with LIPUS, 95% confidence interval 7.7% earlier to 14.3% later; moderate certainty) or the number of subsequent operations (risk ratio 0.80, 95% confidence interval 0.55 to 1.16; moderate certainty). For pain, days to weight bearing, and radiographic healing, effects varied substantially among studies. For all three outcomes, trials at low risk of bias failed to show a benefit with LIPUS, while trials at high risk of bias suggested a benefit (interaction P<0.001). When only trials at low risk of bias trials were considered, LIPUS did not reduce days to weight bearing (4.8% later, 4.0% earlier to 14.4% later; high certainty), pain at four to six weeks (mean difference on 0-100 visual analogue scale: 0.93 lower, 2.51 lower to 0.64 higher; high certainty), and days to radiographic healing (1.7% earlier, 11.2% earlier to 8.8% later; moderate certainty).Conclusions Based on moderate to high quality evidence from studies in patients with fresh fracture, LIPUS does not improve outcomes important to patients and probably has no effect on radiographic bone healing. The applicability to other types of fracture or osteotomy is open to debate.Systematic review registration PROSPERO CRD42016050965

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Effect of Low‐Intensity Pulsed Ultrasound on Distraction Osteogenesis Treatment Time

Cited by 29 publications

References 37 publications

Low Intensity Pulsed Ultrasound for Accelerating Distraction Osteogenesis: A Systematic Review of Experimental Animal Studies

Low Intensity Pulsed Ultrasound for Accelerating Distraction Osteogenesis: A Systematic Review of Experimental Animal Studies

Ultrasound as a stimulus for musculoskeletal disorders

Low intensity pulsed ultrasound for bone healing: systematic review of randomized controlled trials

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